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Cohen Lab

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Use the links above to return to the Cohen Lab homepage or another section.

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Cohen Lab

Papers from the lab

Ryan, Max, Clarice and Jeff all had papers published recently! You can find the links to the papers in the Publications section.

Shown above are cool illustrations that describe Clarice's and Jeff's papers. Can you spot the molecular players in these?

Jeff, Bagel, Beer – Lab Meeting 05/27/2021

Jeff
Genome
Genetics
Phonetics
Photon
Roton
Rotor
Motor
Money
Honey
Bunny
Bagel
Kegel
Candy
Dandy
Dandruff
Beard scruff
Beer
Fear
Deer
Donuts

Credit – Jeff Hansen

Details kill – Lab meeting 05/20/2021

No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.

Credit – Yawei Wu

There once were some yeast – Lab Meeting 05/13/2021

There once were some yeast from afar
That simply would not PCR
Boiling, freezing were no use
So they got ground up and juiced
And now show their genetic scars

Credit – Kai Loell

Insulator – Lab meeting 04/01/2021

It hides in black and dark genomic space
Though with enhancers it must intervene
And once called junk by many in old days
It found fame in the chicken globin gene.
The saw cHS4 had magic game
The researchers who found it thus cried out
O insulator thou art not the same
Now with you loops will never be in doubt.
But then one day a graduate student thought
I wonder how you’ll fare in landing pads
Alas her efforts always came to naught
Much time was wasted chasing it in labs.
But stay, be patient, one day you will see
It will be fucking understood by me.

Credit – Clarice Hong

O lentivirus – Lab Meeting 03/11/21

O lentivirus,
Will you please make more cells green,
Wonder what I’ll find.

Credit – Avinash Ramu

A puzzle – Lab meeting 03/04/21

Swapping out k-mers
Elements become too active
Small changes puzzle me

Credit – Mike White

Spot – Lab meeting 02/11/2021

See Spot run
See Spot scan
See Spot wait for exposing sites
See Spot bind
See Spot take
See Spot outcompete nucleosomes
See Spot spread
See Spot’s friends
See Spot create accessibility
See Spot wave
See Spot call
See Spot recruit transcriptional machinery
See Spot smile
See Spot cheer
See Spot reprogram to a happy lineage
Is Spot weird?
Is Spot cool?
No, Spot is just like all of the other transcription factors!

Credit – Jeff Hansen

Cell walls don’t crumble – Lab meeting 02/04/2021

Cell walls don’t crumble
DNA’s nowhere to see
Will Fluors light the way?

Credit – Kai Loell

One last thing before I go – 01/28/2020

chose artist’s home, for
science is self expression.
found beauty in truth.

This was Max’s last lab meeting with us. Max also shared some words of wisdom with us.

Words of Wisdom

  • Mentoring matters
  • Teaching will make you a better researcher and research will make you a better teacher
  • The goal of the lab is to help lab members get to where they want to go
  • Love people for their strengths and support them through their weaknesses
  • Science is a form of self expression
  • Trust your esthetic taste in problems and answers.
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Cohen Lab

The student – Lab meeting 01/21/21

The student, she felt some distress,
That the QE could end up a mess.
She thought there’d be questions aplenty.
But the Profs’ heads were actually empty,
And the exam was a smashing success!

Credit – Barak Cohen

What is this sequence – Lab meeting – 01/14/2021

What is this sequence–
Strong, silent, or inactive?
It’s all in the bits.

Credit – Ryan Friedman

Haiku was here – Lab meeting 12/17/2020

Haiku was here

From ashes of sparks,
Poets pick up left pieces,
“Hey! Poems were here”

Credit – Yawei Wu

If one sings about the invisible, and to Calvino – Lab Meeting 12/03/2020

If one sings about the invisible, and to Calvino
These cities Marco Polo told the Khan,
Which are forgotten by memory now,
Only shadows exist and else are gone.
Oh Where? In Levantine but no one saw.
Ooh! A human cries for joy not for pain,
Only in Diomera with damascened wall;
And Isidora, before her all fain,
In endless desires memory is all.
It’s real? The Great Khan asks, with his back bent.
Does it matter? As light as a feather
Polo’s answer is outside the present,
Just as daydreams, do not wither.
To feel the subtlety of foreverness,
And to kiss the pain of experience.

Credit – Siqi Zhao

Zoom – Lab Meeting 11/19/2020

Your face frozen on
my screen. These days we all have
limited bandwidth.

haiku by Janni Lee Simner, shared by Dustin

Brad – Lab Meeting 10/15/20

There once was a promoter called Brad
Who flew to a landing pad
He left in style
But landed in hell
He makes me a little mad

Credit – Clarice Hong

Jeff is a transcription factor – Lab meeting 09/24/20

Pursuit

Jeff biked off to find a good beer
But only closed breweries would appear
Good thing he was a pioneer developmental transcription factor
He broke in with his zinc retractor
And drank all the night with good cheer

Credit – Jeff Hansen

A TF ponders – Lab meeting 08/27/20

On the sense strand a TF pondered,
“Which way to the enhancer I wonder?”
Should I follow the loop,
through this phase separate soup?
Or hitch a ride with my pal p300?

Credit – Barak Cohen

Rainbow

Look what our intrepid observer Yawei spotted outside. It seems that stay-at-home won’t stop us from making observations. Imagine that you are the first human to ever observe a rainbow, how would you explain it? Or would you rather just enjoy it?

A computationalist’s lament – Ryan’s lab meeting 8/20/20

Stay home? No problem! My work won’t be quenched.
After all, things in lab can make quite a stench.
But one fifty seven days
of work from home craze
makes me wish I did more at the bench.

Credit – Ryan Friedman

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Cohen Lab

Mutants, brawn and bereavement from Nicole’s lab meeting – 8/13/20

There once was a zygote conceived
Whose genome mutated with ease
The mutations plopped on
With great strength and brawn
And now the parents are bereaved

Credit – Nicole Rockweiler

Gene regulation and fruit from a tree – Yawei’s lab meeting 8/7/20

Yawei started lab meeting with a cartoon depicting a model of gene regulation. See if you can figure out the analogy.

Image credit – Yawei Wu

Haiku – Siqi’s lab meeting 7/30

Of those sleepless nights,
how many did you consume,
stochasticity?

Credit – Siqi Zhao

Virtual Reunion

The virtual celebration for Dana’s paper turned into a lab Zoom reunion on April 7, 2020. It was great to see everyone who could make it and hear stories from different eras of the lab.

First Cohen Research Conference

The first-ever Cohen Research Conference was held Feb 25-27, 2020 at Stonehaven Castle, Eureka Springs, AR. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board-games, day-time and night-time hikes, a meditation session, sciencing around a campfire, spotting constellations on a clear black sky, balancing the entire lab on a log, and impromptu midnight performances with the guitar by Barak. It was a truly special experience. Thanks to Clarice and Jeff, the chief organizers of the conference.

Photo credit: James

Sailing fun

The lab spent a fun day sailing on Barak’s boat last week. The weather obliged with some great sunshine and good winds. The rejuvenated crew are now back in the lab to tackle smaller amounts of liquid.

Photo credit: James

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Cohen Lab

Posts by Hemangi

Listen to Barak’s Podcast with Shelina!

You can listen to the podcast here.

Brett Maricque, interviewed on “St. Louis on the Air”

Graduate student and current BALSA president, Brett Maricque, and co-founder, Maxim Schillebeeckx, discuss how the BALSA group allows graduate students to gain business experience while providing quality, low cost consulting services for the growing St. Louis biotechnology sector and generating grant money for local entrepreneurs through the BALSA Foundation. Listen to the full conversation on the “St. Louis on the Air” website.

Marc Sherman receives prestigious Spencer T. and Ann W. Olin Medical Science Fellowship

The Olin Fellowships recognize accomplishments in biomedical research by doctoral students at Washington University. While thirty-two students were nominated, only eight awards were granted. Marc’s research focused on stochasticity in gene expression and the kinds of “noise” that are often disregarded when expression is measured. While he has moved on to his clinical rotations, Marc’s work in the Cohen lab can be found under our publications header.

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Cohen Lab

Fourth Cohen Research Conference

The fourth annual Cohen Research Conference was held October 23-25, 2023 in Michigan City, IN. Lab members presented talks on big ideas or out-there experiments. Continuing the tradition from prior CRCs, we also enjoyed communal cooking, a campfire near the lake, and a dunes hike in Indiana Dunes National Park which passed through Cowles Bog, a site of seminal research on ecological succession!

Goodbye Ryan, Avi, and Kai!

The lab met at Barak's house to congratulate Ryan, Avi and Kai on their successful thesis defenses and wish them well in their next endeavors! Ryan will be starting a postdoc in Cole Trapnell's lab at UW, Avi will be joining the team at Verily Life Sciences, and Kai will be starting a postdoc in Justin Kinney's lab at CSHL.

Well done, Kai!

Congratulations to Kai Loell for bringing the Cohen lab defense record to 3/3 this week by successfully defending his thesis, "Biophysically-informed models of heterogeneity in transcription factor activity"! Watch a recording of the defense here.


Attachments

Congratulations Avi!

The second of three in this week's Cohen lab defense-o-rama — congratulations to Avi Ramu for successfully defending his thesis, "Sources and consequences of cell-to-cell variability in gene expression"! Watch a recording of the defense here.


Attachments

Congratulations Ryan!

Congratulations to Ryan Friedman for kicking off the Cohen lab's three-defense week by successfully defending his thesis, "Iterative machine learning of a cis-regulatory grammar"! Watch a recording of the defense here.


Attachments

Summer Cookout — Goodbye, Jeff and Siqi!

The lab joined family and friends to celebrate Jeff and Siqi's successful defenses with a backyard cookout! Barak presented a book to each of the graduates, and everyone was treated to a magic show … um, I mean scientific demonstration of the power of ESP.

Congratulations Siqi!

Congratulations to Siqi Zhao for a successful defense of his thesis, “Single-cell massively parallel reporter assays”, completing the Cohen lab June thesis defense double-header! Watch a recording of his defense here!


Attachments

Congratulations Jeff!

Congratulations to Jeff Hansen for a successful defense of his thesis, “A Test of the Pioneer Factor Hypothesis for Silent Gene Activation”. Watch a recording of his defense here. Jeff is an MSTP student and will be returning to the clinic for the final two years of Medical School, so we still hope to see him around!


Attachments

Second Cohen Research Conference

The second Cohen Research Conference was held September 13-15, 2021 at Lake Geneva, WI. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board games, swimming and kayaking, a lakeside hike, a meditation session, science talks out on the deck, and more! A strong continuation of CRC tradition. Thanks to Clarice and Jeff, the chief organizers of the conference.

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Cohen Lab

We do science, too

We have a lot of fun in the Cohen Lab. We sail, and we eat donuts, and we brainstorm big ideas over tasty cocktails. But at core, we are a band of renegades, uncovering secrets of the genome. The only evidence for that claim that you’ll need is the picture below, showing Max and Maria and Clarice taking care of their cells, on a Cohen-Triple-TC-Hood-Combo-Day.

Back to back to back!

Congratulations to Clarice, to Siqi, and to Jeff on successfully proposing their theses! The three have hitched their wagons together so as one wagon advances ahead, the others are pulled alongside. In such a way, the three have boosted each other’s science and buoyed each other’s spirits. A regular Cerberus of science. What a team!

We look forward to seeing what comes out of each one’s thesis work.

Sailing through graduate school

When a few Cohen Lab members found themselves listlessly floating through the doldrums of graduate school, Barak came to the rescue. Quickly navigating rivers and creeks and roadside puddles, he sailed across Illinois and arrived in lab to the shock and awe of the other landlubber labs. His new crew gave a quick “yippee” and climbed aboard.

Might there be merits to guiding the ship into international waters where the rogue scientists could set up a nautical lab? Benefits would include easy access to fresh seafood, plenty of salt water for buffering our enzymatic reactions, and the inspiration of the fresh sea breeze. That said, we may need to invent new nautical approaches to sequencing DNA, discover internet-free ways of reading new papers, and identify some Atlantis-based funding source.

For now, we’ll keep residence within our lovely coffee-laden abode and escape to Carlyle Lake when the siren song becomes too much. But when the floods arrive again, look to the Cohen Lab for the beginnings of the NNIH: the National Nautical Institutes of Health.

Donut Day in the Cohen Lab

Mary Poppins sang that a spoonful of sugar helps the medicine go down. This morning, we sang that a dozen John’s donuts helps the Washington University in St. Louis Institutional Biological & Chemical Safety Committee Protocol go down, and an additional spoonful of sugar helps that lengthy name go down.

Around the rooster’s crow, Barak, Max, Clarice, and Jeff gathered round a table piled high with past protocols, laptops, safety certificates, and a hearty collective knowledge ranging from the origins of reporter genes to the dangers of graphite in space. And then there were the donuts. Our lab has a storied tradition of sweetening unpleasant days with samplings of St. Louis’ fabulous donut scene. For RNA extractions, we grab a dozen from World’s Fair. For library preparation, we grab a dozen from Vincent Van Doughnut. For Clarice’s seven-hour-long marathon of a practice talk, we grab a dozen from Strange. And for the latest effort in maintaining a safe and accountable lab, we grab a dozen from John’s.

Perched next to our venerable coffee source, the four toiled as the sun progressed across the sky. Time’s passing was marked only by the regular flow of fellow scientists, coming to refill their receptacles with the dark brown life fuel that surely represents far too high of a proportion within our electrolyte-deficient bloodstream. Some offered sympathies, while others jealously eyed the donuts. The latter group hoped to only experience the sweet without the accompanying sour.

As the crescent moon rose on the horizon, the protocol neared complete. The four, splitting the final donut into quarters, each raised a piece in cheers to renewed safety and accountability. And quickly retired from lab to find some vegetables.

Big Ideas Night

Aaaand we’re back for round three. This time with some new faces! Ah, time ticks on and people come and go. Fortunately for us, whiskey and science persist.

Back at the Scottish Arms, we tackled the problem of detecting simultaneous binding of two proteins to DNA; the proteins each must bind to the DNA and thus are not co-localized due to protein-protein interactions. In Barak’s words…imagine the TF a cowboy. Once on its DNA horse, it can lasso other TFs around it, but only those TFs also on horses. A wild west of a genome, indeed.

Some ideas included FRET-seq, 2-dimensional gels, and combination usage of accessibility and binding footprints. Without a clear winner, we’ll wait another day before discarding the lassos hanging from our bench top shelves. Until next time, keep thinking big, you crazy scientists.

Reflection upon a passed qualifying exam

Today in lab we were calling each other “champ”. My mom calls me Jeff. I passed my qualifying exam last Friday. Instead of providing you the blow-by-blow of my lively discussion on what sequence features determine pioneering activity, I will reflect. I hope to convey how positive an environment a lab can be.

As an MD-PhD student, I completed two years of classroom medical school prior to starting my PhD. During those first two years, I took many exams. Each exam was a real battle – from memorizing each drug used to treat heart failure to understanding how the kidney uses a litany of channels to filter our blood. By design, these two years were me against the knowledge base. Indirectly though, it was me against my classmates as we vie for a limited number of spots in competitive specialties. The result was that at times the crushing individualism led to lonely isolation.

What a difference the Cohen lab has been. A tradition of committing ourselves to each others’ crafts defines the lab, and defines the research environment at WashU. As my talk rose on the horizon, my lab mates gathered around our cozy conference table and spent hours helping me hone my ideas and sharpen my arguments to send me towards my QE. And as I stepped out of the room as my committee deliberated, there was Clarice down the hall with a wide grin on her face welcoming me back into the arms of the lab.

While the day-to-day life of medical and graduate school differ greatly, each focuses on the pursuit of knowledge. In my experience, one goes about that individually and one goes about that collaboratively. And I thank the cloning gods above that I found myself amongst the champs of Barak’s lab.

Farewell, Hemangi!

On Sunday, Barak hosted a farewell brunch for our senior graduate student, Hemangi Chaudhari. Beyond her contributions to the scientific community, Hemangi has provided wisdom and guidance to our lab for several years now. To the younger graduates, she provided patient instruction. To her classmates, she provided unbeatable cuisine and loyal companionship. And to post-docs and PIs, she provided an intellectual debate over the implications of a result or the design of an experiment.

As Hemangi moves to Boston, we wish her the warmest farewell. As she leaves behind her pipettes (to be scrounged after by incoming students) she leaves a lasting mark on both the lab and the scientific trajectories of those that were lucky enough to spend time with her in St. Louis. We all hope to cross paths again soon, as we crisscross through scientific communities all pointed towards a greater understanding of biology. While the farewells may be blue, the difficulty in parting demonstrates how strong the connections developed to be.

Farewell, Hemangi! We’ll see you again soon!

Image: Masala dosa – featured at the farewell brunch – every bite cherished (source: NY Times).

Bissinger’s Chocolate Factory Tour

In an effort to find something sweeter than the satisfaction of sequencing DNA, the lab trekked downtown to visit St. Louis’ own Bissinger’s Chocolate Factory. Led by a couple of chocolate fanatics, we sought to uncover the secrets behind this famous chocolate. But alas, our phones were confiscated and the chocolate-factory-dungeon was threatened if we strayed from the walkway and became too pesky of visitors.

On our tour, we learned of the hand-crafted nature of Bissinger’s chocolate. A few lab members couldn’t help but be reminded of how we too take care to make sure that every library we design receives high quality and individualized attention. After the tour, we were treated to a tasting. Barak liked the chocolate-covered cherries. Siqi preferred the milk chocolate over the dark chocolate. Clarice quipped that her mint chocolate tasted like toothpaste.

All in all, we had a wonderful time. Was it sweeter than that feeling of opening up your sequencing results to find a beautiful array of A’s, C’s, T’s and G’s? Maybe not, but alas the factory was neat and the chocolate was tasty.

Qualifying Exam Successes

Congratulations to Clarice Hong (Molecular Genetics and Genomics) and Siqi Zhao (Computational and Systems Biology) on passing their Qualifying Exams!!! They have their wagons hitched to a star and we can’t wait to see where their scientific adventures travel next.

Big Ideas Night

Following the smashing success of our first big ideas night, big ideas coated our benches just as Barak’s wool sweater once did. Ideas so big that we contemplated moving into a building with even higher ceilings. But alas, we shan’t desert our loyal coffee maker, so we stay put.

The second gathering of Big Idea’s Night took place at Retreat Gastropub. Amidst some fries and whiskey, we pitched ideas for how we can utilize our Center’s newest sequencing technologies. PacBio’s ultra-long sequencing reads and the 10x single-cell method both provide new avenues for innovative research. And to not exclude our friends in imaging, we discussed a new application of FISH, called clampFISH. This technology generates a FISH signal strong enough to be detected by FACS.

The idea most discussed utilizes ultra-long reads to query chromatin interactions. In our lab, we have identified strong regional effects on gene expression. How far do these regions stretch? With our landing pad in place, we can integrate reporter genes at variable distances and ask how the length relates to the coordinated expression between the reporter gene at the LP and at distance. If we see discordance at a certain distance, it may be possible to restore the similar expression with looping-related proteins, such as CTCF or YY1. As team landing pad ventures further into the mechanisms of this strong regional effect, we will draw from these discussions and this big idea.

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Cohen Lab

Hemangi’s Thesis Defense

Our intrepid landing pad explorer has successfully defended her thesis, titled “Integration of local and regional regulatory information in the human genome”!!!

Afterwards, we toasted champagne and had delicious Himalayan Yeti as we recounted Hemangi’s many wonderful accomplishments.

Big Ideas Night

The inaugural Cohen Lab Big Ideas Night! Barak loves to tell the story of the discovery of transfer RNA. Our scientific forefathers kicked around ideas over tea, scones, and maybe some beers too. Through this sort of brainstorming, the idea that there must be some molecule shuttling around amino acids was borne. Once our forefathers convinced themselves of the specifics of the idea, and how the experiment would work, actually conducting it became trivial. And thus tRNA was discovered. If such great biological discovery can be made over scones and ales, then lets indulge!

Settled into our lab’s old haunts, The Scottish Arms, we bounced around big ideas focused on master regulators. With new graduate students patrolling the benches, the lab has taken up new vocabulary as well: pioneer factors. Discussion flitted between definition, mechanism, and proof of these special transcription factors; perhaps we leave this discussion for our graduate students’ future presentations.

And so big idea #1 was not as much an idea but an open question: what would result from treating cells with two different master regulator cocktails? What type of cell would the transcriptome resemble? Would we see a random assortment of cell A and cell B, or would we see a monster, with the head of cell A and the body of cell B? With Halloween on the horizon, we’ll incubate this spooky idea until a rainy day comes along, ripe with time for a big idea experiment.

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Cohen Lab

AI Art Gallery in Barak's Office

When the PI is away, the grad students play!

Every year when Barak goes out of town for a long time, we prank his office as a welcome back surprise. Barak has recently taken a strong interest in Paul Cezanne, so this year we turned his office into an art gallery. We used the AI DALL-E 2 to generate fake art and hung it next to real art. We used another AI called ChatGPT to generate fake museum labels to accompany the fake art.

In addition, James used 24 photos of Barak from over the years and the "Dreambooth" technique to teach another AI, Stable Diffusion, what Barak looks like. Then, James asked Stable Diffusion to generate portraits of Barak in the style of several different artists. The collection of portraits is truly stunning -- there's even a museum label from ChatGPT emphasizing the mystery of the portraits' recurring subject!

Here are some pictures of the decor. Can you tell which pieces are real works of art?

Below is what ChatGPT had to say about the portrait collection:

"The Many Faces of _______: A Portrait Collection"

This collection features a series of portrait paintings, all depicting the same individual. The artwork on display was created by a diverse group of artists, each bringing their own unique style and perspective to the portrayed subject.

Who was this person, and why were they painted by so many different artists? These paintings offer a glimpse into the life and personality of the subject, but leave much to the imagination.

From the traditional techniques of the Old Masters, to the bold brushstrokes and vibrant colors of modern art, this collection showcases the versatility and enduring appeal of portraiture. The subjects depicted range from formal poses in elegant attire, to more relaxed and casual depictions.

Despite the varied styles and approaches, each of these paintings captures the essence of the subject and conveys a sense of their personality. This collection serves as a testament to the enduring power of portraiture as a means of preserving the human spirit on canvas, and leaves us wondering about the mystery of the person depicted.

Congratulations Clarice!

Congratulations to Clarice Hong for successfully defending her thesis, "Understanding gene regulation with high-throughput genome-integrated reporter assays"! Watch a recording of her defense here.

Third Cohen Research Conference

The third annual Cohen Research Conference was held October 17-19, 2022 in Cadiz, KY. Everyone presented a talk about big questions or ideas they have. We also enjoyed communal cooking, a campfire near the water, a hike through the Land Between the Lakes National Recreation Area, moonshine tasting, puzzles and board games, guitar performances by Barak and rotation student AJ, and more! We also stopped in Metropolis, IL to see a 15-foot statue of Superman. A great time was had by all. The CRC has certainly been cemented as a lab tradition!

Photo credit: James

New Paper from the Lab

Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats Kai!

Cohen Lab attends ASBMB meeting

Mike, Clarice, Ryan, Kai, and Yawei recently traveled to the Stowers Institute in Kansas City to attend the ASBMB conference "Evolution and Core Processes in Gene Expresson". Clarice gave a talk and everyone else presented a poster. Congratulations to Yawei, who was awarded a Best Poster Award for a graduate student!

We had a great time learning about the latest research in cis-regulatory grammar, enhancer evolution, and predictive models of gene regulation. We also enjoyed eating some delicious Kansas City BBQ and connecting with our peers and colleagues in the field.

Congratulations Siqi!

Congratulations to Siqi Zhao for a successful defense of his thesis, “Single-cell massively parallel reporter assays”, completing the Cohen lab June thesis defense double-header! Watch a recording of his defense here!


Attachments

Congratulations Jeff!

Congratulations to Jeff Hansen for a successful defense of his thesis, “A Test of the Pioneer Factor Hypothesis for Silent Gene Activation”. Watch a recording of his defense here. Jeff is an MSTP student and will be returning to the clinic for the final two years of Medical School, so we still hope to see him around!


Attachments

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Post Authors

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Cohen Lab

Contact

Mailing Address

Cohen Lab
Couch Biomedical Research Building
CAMPUS BOX #8510
4523 CLAYTON AVE
SAINT LOUIS, MO 63110

Phone

Office: 314-362-3674
Lab: 314-362-3679
Fax: 314-362-7855

Email

cohen [at] wustl.edu

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Cohen Lab

Between the Genes: The Genomics of Gene Regulation

Vast tracts of non-coding genomic DNA separate the tiny portions of the human genome that code for our genes. Scattered throughout this non-coding DNA are enhancers — short DNA sequences that control when, where, and to what extent the genes are transcribed. Enhancers orchestrate the intricate patterns of gene expression that direct normal development and physiology in all organisms. The importance of enhancers is underscored by the fact that the majority of disease-causing variants in the human genome reside not in but between the genes, where they disrupt normal gene expression, in part by interfering with the function of enhancers.

Because of their importance in development and disease, we are trying to understand the DNA sequence features that control the activity and specificity of enhancers and other cis-regulatory elements. We take a multidisciplinary approach to this problem, employing both experimental and computational approaches borrowed from genetics, genomics, systems biology, synthetic biology, biophysics, computer science, and statistical physics. Ultimately, we hope to produce quantitative models that accurately identify new regulatory sequences in the genome and predict the consequences of mutations in these elements. Such models will be critical tools for understanding normal development, as well as diseases caused by non-coding mutations.

Positions

The Cohen Lab is currently seeking motivated postdocs. Interested applicants should contact Barak with a cover letter and CV.

Selected Publications

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Cohen Lab

Journal Club

The Cohen Lab journal club meets at 10:00 AM on Wednesdays in Couch 4304.

Every few weeks, each lab member pitches an article that they have recently read. They have two minutes to sell the lab on the exciting findings and merits of the experiments. At the conclusion, the lab votes on the papers that will populate the coming weeks’ discussions.

Previously-Discussed Papers

1/3/24: Elias T.F et al. Ultra-long-range interactions between active regulatory elements. Genome Research (2023) [doi: 10.1101/gr.277567.122]

12/20/23: Matthew P.S et al. RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size. Cell (2023) [doi: 10.1016/j.cell.2023.10.012]

12/13/23: Evgenia N et al. Genome-wide measurement of RNA dissociation from chromatin classifies transcripts by their dynamics and reveals rapid dissociation of enhancer lncRNAs. Cell Systems (2023) [doi: 10.1016/j.cels.2023.09.005]

12/6/23: Ilias G-S et al. High-throughput characterization of the role of non-B DNA motifs on promoter function. Cell Genomics (2022) [doi: 10.1016/j.xgen.2022.100111]

11/29/23: Andreas R.G et al. An encyclopedia of enhancer-gene regulatory interactions in the human genome. bioRxiv (2023) [doi: 10.1101/2023.11.09.563812]

11/8/23: Patil A et al. A disordered region controls cBAF activity via condensation and partner recruitment. Cell (2023) [doi: 10.1016/j.cell.2023.08.032]

11/1/23: Horton CA et al. Short tandem repeats bind transcription factors to tune eukaryotic gene expression. Science (2023) [doi: 10.1126/science.add1250]

10/18/23: Pownall ME et al. Chromatin expansion microscopy reveals nanoscale organization of transcription and chromatin. Science (2023) [doi: 10.1126/science.ade530]

10/11/23: Quililan K et al. In vitro reconstitution of chromatin domains. bioRxiv (2023) [doi: 10.1101/2023.02.27.530214]

9/20/23: Hawkins JA et al. Indel-correcting DNA barcodes for high-throughput sequencing. PNAS (2023) [doi: 10.1073/pnas.1802640115]

9/20/23: Press WH et al. Fast trimer statistics facilitate accurate decoding of large random DNA barcode sets even at large sequencing error rates. PNAS Nexus (2023) [doi: 10.1093/pnasnexus/pgac252]

9/13/23: Oksuz O et al. Transcription factors interact with RNA to regulate genes. Molecular Cell (2023) [doi: 10.1016/j.molcel.2023.06.012]

9/6/23: Jacobs J et al. Widespread regulatory specificities between transcriptional co-repressors and enhancers in Drosophila. Science (2023) [doi: 10.1126/science.adf6149]

8/30/23: Goyal Y et al. Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells. Nature (2023) [doi: 10.1038/s41586-023-06342-8]

8/23/23: Jonathan L et al. Different chromatin-scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2. Cell Reports (2023) [doi: 10.1016/j.celrep.2023.112748]

8/2/23: Yoon JK et al. Light-activated macromolecular phase separation modulates transcription by reconfiguring chromatin interactions. Science Advances (2023) [doi: 10.1126/sciadv.adg1123]

7/26/23: Matthew AB et al. Temperature-dependent RNA editing in octopus extensively recodes the neural proteome. Cell (2023) [doi: 10.1016/j.cell.2023.05.004]

7/19/23: Nicole D et al. Large-scale mapping and mutagenesis of human transcriptional effector domains. Nature (2023) [doi: 10.1038/s41586-023-05906-y]

7/12/23: Koji K et al. Functional coordination between transcription factor clustering and gene activity. Molecular Cell (2023) [doi: 10.1016/j.molcel.2023.04.018]

7/12/23: Joseph M et al. Transcription factor clusters enable target search but do not contribute to target gene activation. Nucleid Acid Research (2023) [doi: 10.1093/nar/gkad227]

6/21/23: Song BP et al. Diverse logics and grammar encode notochord enhancers. Cell Reports (2023) [doi: 10.1016/j.celrep.2023.112052]

6/14/23: Zhou Z et al. Engineering longevity—design of a synthetic gene oscillator to slow cellular aging. Science (2023) [doi: 10.1126/science.add7631]

6/7/23: Kumar DBU et al. A genome–wide CRISPR activation screen identifies SCREEM a novel SNAI1 super-enhancer demarcated by eRNAs. Frontiers in Molecular Biosicences (2023) [doi: 10.3389/fmolb.2023.1110445]

5/31/23: Naqvi S et al. Precise modulation of transcription factor level/s identifies features underlying dosage sensitivity. Nature Genetics (2023) [doi: 10.1038/s41588-023-01366-2]

3/15/23: Kim YJ et al. Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer. eLife (2022) [doi: 10.7554/eLife.73395]

3/8/23: Chakraborty S et al. Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness. Nature Genetics (2023) [doi: 10.1038/s41588-022-01295-6]

2/22/23: Anderson AG et al. Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer’s disease-specific cis-regulatory elements. Cell Genomics (2023) [doi: 10.1016/j.xgen.2023.100263]

2/15/23: Yanchus C et al. A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation. Science (2022) [doi: 10.1126/science.abj2890]

1/25/23: Economou A et al. Nodal signaling establishes a competency window for stochastic cell fate switching. Developmental Cell (2022) [doi: 10.1016/j.devcel.2022.11.008]

1/11/23: Hsieh TS et al. Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1. Nature Genetics (2022) [doi: 10.1038/s41588-022-01223-8]

1/4/23: Daniels KG et al. Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning. Science (2022) [doi: 10.1126/science.abq0225]

12/22/22: Lalanne JB et al. Multiplex profiling of developmental enhancers with quantitative, single-cell expression reporters. bioRxiv (2022) [doi: 10.1101/2022.12.10.519236]

11/9/22: Ray et al. A mechanism for oxidative damage repair at gene regulatory elements. Nature (2022) [doi: 10.1038/s41586-022-05217-8]

11/2/22: Morin et al. Sequence-dependent surface condensation of a pioneer transcription factor on DNA. Nature Physics (2022) [doi: 10.1038/s41567-021-01462-2]

10/5/22: Asimi V et al. Hijacking of transcriptional condensates by endogenous retroviruses. Nature Genetics (2022) [doi: 10.1038/s41588-022-01132-w]

9/14/22: Lin X et al. Nested epistasis enhancer networks for robust genome regulation. Science (2022) [doi: 10.1126/science.abk3512]

9/7/22: Pachano T et al. Orphan CpG islands amplify poised enhancer regulatory activity and determine target gene responsiveness. Nature Genetics (2021) [doi: 10.1038/s41588-021-00888-x]

8/31/22: Neumayr C et al. Differential cofactor dependencies define distinct types of human enhancers. Nature (2022) [doi: 10.1038/s41586-022-04779-x]

8/17/22: Bergman DT et al. Compatibility rules of human enhancer and promoter sequences. Nature (2022) [doi: 10.1038/s41586-022-04877-w]

8/10/22: Bal E et al. Super-enhancer hypermutation alters oncogene expression in B cell lymphoma. Nature (2022) [doi: 10.1038/s41586-022-04906-8]

8/3/22: Choi J et al. A time-resolved, multi-symbol molecular recorder via sequential genome editing. Nature (2022) [doi: 10.1038/s41586-022-04922-8]

7/13/22: Konstantinides N et al. A complete temporal transcription factor series in the fly visual system. Nature (2022) [doi: 10.1038/s41586-022-04564-w]

7/6/22: Snetkova V et al. Ultraconserved enhancer function does not require perfect sequence conservation. Nature Genetics (2021) [doi: 10.1038/s41588-021-00812-3]

6/8/22: Ma Y et al. Synthetic mammalian signaling circuits for robust cell population control. Cell (2022) [doi: 10.1016/j.cell.2022.01.026]

5/18/22: Topolewski P et al. Phenotypic variability, not noise, accounts for most of the cell-to-cell heterogeneity in IFN-gamma and oncostatin M signaling responses. Science Signaling (2022) [doi: 10.1126/scisignal.abd9303]

4/19/22: Marklund E et al. Sequence specificity in DNA binding is mainly governed by association. Science (2022) [doi: 10.1126/science.abg7427]

4/13/22: Rao S et al. Cooperative binding between distant transcription factors is a hallmark of active enhancers. Molecular Cell (2021) [doi: 10.1016/j.molcel.2021.02.014]

4/6/22: Traets JJH et al. Mechanism of life-long maintenance of neuron identity despite molecular fluctuations. eLife (2021) [doi: 10.7554/eLife.66955]

3/23/22: Ursu O et al. Massively parallel phenotyping of coding variants in cancer with Perturb-seq. Nature Biotechnology (2022) [doi: 10.1038/s41587-021-01160-7]

2/23/22: Seczynska M et al. Genome surveillance by HUSH-mediated silencing of intronless mobile elements. Nature (2022) [doi: 10.1038/s41586-021-04228-1]

2/2/22: Duveau F et al. Mutational sources of trans-regulatory variation affecting gene expression in Saccharomyces cerevisiae. eLife (2021) [doi: 10.7554/eLife.67806]

1/26/22: Bintu L et al. Dynamics of epigenetic regulation at the single-cell level. Science (2016) [doi: 10.1126/science.aab2956]

12/8/21: Hocker JD et al. Cardiac cell type-specific gene regulatory programs and disease risk association. Science Advances (2021) [doi: 10.1126/sciadv.abf1444]

11/10/21: Rinzema NJ et al. Building regulatory landscapes: enhancer recruits cohesin to create contact domains, engage CTCF sites and activate distant genes. bioRχiv Preprint (2021) [doi: 10.1101/2021.10.05.463209]

11/3/21: de Almeida BP et al. DeepSTARR predicts enhancer activity from DNA sequence and enables the de novo design of enhancers. bioRχiv Preprint (2021) [doi: 10.1101/2021.10.05.463203]

10/27/21: Li YE et al. An atlas of gene regulatory elements in adult mouse cerebrum. Nature (2021) [doi: 10.1038/s41586-021-03604-1]

10/20/21: Garcia DA et al. An intrinsically disordered region-mediated confinement state contributes to the dynamics and function of transcription factors. Molecular Cell (2021) [doi: 10.1016/j.molcel.2021.01.013]

10/6/21: Child MB et al. Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila. eLife (2021) [doi: 10.7554/eLife.64412]

9/29/21: Wan YH et al. Dynamic imaging of nascent RNA reveals general principles of transcription dynamics and stochastic splice site selection. Cell (2021) [doi: 10.1016/j.cell.2021.04.012]

9/8/21: Zhang YN et al. Competition for DNA binding between paralogous transcription factors determines their genomic occupancy and regulatory functions. Genome Research (2021) [doi: 10.1101/gr.275145.120]

9/1/21: Desai RV et al. A DNA repair pathway can regulate transcriptional noise to promote cell fate transitions. Science (2021) [doi: 10.1126/science.abc6506]

8/25/21: Soochit W et al. CTCF chromatin residence time controls three-dimensional genome organization, gene expression and DNA methylation in pluripotent cells. Nature Cell Biology (2021) [doi: 10.1038/s41556-021-00722-w]

8/18/21: Tak YE et al. Augmenting and directing long-range CRISPR-mediated activation in human cells. Nature Methods (2021) [doi: 10.1038/s41592-021-01224-1]

7/21/21: Sanford EM et al. Gene regulation gravitates toward either addition or multiplication when combining the effects of two signals. eLife (2020) [doi: 10.7554/eLife.59388]

7/14/21: Sonmezer C et al. Molecular Co-occupancy Identifies Transcription Factor Binding Cooperativity In Vivo. Molecular Cell (2021) [doi: 10.1016/j.molcel.2020.11.015]

7/7/21: Tycko J et al. High-Throughput Discovery and Characterization of Human Transcriptional Effectors. Cell (2020) [doi: 10.1016/j.cell.2020.11.024]

6/30/21: Ng AHM et al. A comprehensive library of human transcription factors for cell fate engineering. Nature Biotechnology (2021) [doi: 10.1038/s41587-020-0742-6]

6/23/21: Li JR et al. Single-gene imaging links genome topology, promoter-enhancer communication and transcription control. Nature Structural & Molecular Biology (2020) [doi: 10.1038/s41594-020-0493-6]

5/12/21: Hanna RE et al. Massively parallel assessment of human variants with base editor screens. Cell (2021) [doi: 10.1016/j.cell.2021.01.012]

5/5/21: Kharerin H, Bai L Thermodynamic modeling of genome-wide nucleosome depleted regions in yeast. PLOS Computational Biology (2021) [doi: 10.1371/journal.pcbi.1008560]

4/28/21: Takei Y et al. Integrated spatial genomics reveals global architecture of single nuclei. Nature (2021) [doi: 10.1038/s41586-020-03126-2]

4/21/21: Emert BL et al. Variability within rare cell states enables multiple paths toward drug resistance. Nature Biotechnology (2021) [doi: 10.1038/s41587-021-00837-3]

4/14/21: Choi J et al. Evidence for additive and synergistic action of mammalian enhancers during cell fate determination. eLife (2021) [doi: 10.7554/eLife.65381]

3/3/21: Henninger JE et al. RNA-Mediated Feedback Control of Transcriptional Condensates. Cell (2021) [doi: 10.1016/j.cell.2020.11.030]

2/24/21: Thomas HF et al. Temporal dissection of an enhancer cluster reveals distinct temporal and functional contributions of individual elements. Molecular Cell (2021) [doi: 10.1016/j.molcel.2020.12.047]

2/17/21: Tanaka H et al. Interaction of the pioneer transcription factor GATA3 with nucleosomes. Nature Communications (2020) [doi: 10.1038/s41467-020-17959-y]

2/10/21: Akdemir KC et al. Somatic mutation distributions in cancer genomes vary with three-dimensional chromatin structure. Nature Genetics (2020) [doi: 10.1038/s41588-020-0708-0]

2/3/21: Klosin A et al. Phase separation provides a mechanism to reduce noise in cells. Science (2020) [doi: 10.1126/science.aav6691]

1/20/21: Bergen V et al. Generalizing RNA velocity to transient cell states through dynamical modeling. Nature Biotechnology (2020) [doi: 10.1038/s41587-020-0591-3]

1/6/21: Domcke S et al. A human cell atlas of fetal chromatin accessibility. Science (2020) [doi: 10.1126/science.aba7612]

12/16/20: Wong ES et al. Deep conservation of the enhancer regulatory code in animals. Science (2020) [doi: 10.1126/science.aax8137]

12/9/20: Kent S et al. Phase-Separated Transcriptional Condensates Accelerate Target-Search Process Revealed by Live-Cell Single-Molecule Imaging. Cell Reports (2020) [doi: 10.1016/j.celrep.2020.108248]

11/11/20: Ballare C et al. Nucleosome-Driven Transcription Factor Binding and Gene Regulation. Molecular Cell (2013) [doi: 10.1016/j.molcel.2012.10.019]

11/4/20: Ireland WT et al. Deciphering the regulatory genome of Escherichia coli, one hundred promoters at a time. eLife (2020) [doi: 10.7554/eLife.55308]

10/21/20: Chiasson MA et al. Multiplexed measurement of variant abundance and activity reveals VKOR topology, active site and human variant impact. eLife (2020) [doi: 10.7554/eLife.58026]

10/14/20: Houri-Zeevi L et al. Three Rules Explain Transgenerational Small RNA Inheritance in C. elegans. Cell (2020) [doi: 10.1016/j.cell.2020.07.022]

10/7/20: Chen SY et al. Optogenetic Control Reveals Differential Promoter Interpretation of Transcription Factor Nuclear Translocation Dynamics. Cell Systems (2020) [doi: 10.1016/j.cels.2020.08.009]

9/23/20: Jaeger MG et al. Selective Mediator dependence of cell-type-specifying transcription. Nature Genetics (2020) [doi: 10.1038/s41588-020-0635-0]

9/16/20: Sigalova OM et al. Predictive features of gene expression variation reveal mechanistic link with differential expression. Molecular Systems Biology (2020) [doi: 10.15252/msb.20209539]

9/9/20: Hoppe C et al. Modulation of the Promoter Activation Rate Dictates the Transcriptional Response to Graded BMP Signaling Levels in the Drosophila Embryo. Developmental Cell (2020) [doi: 10.1016/j.devcel.2020.07.007]

9/2/20: Hafner A et al. Quantifying the Central Dogma in the p53 Pathway in Live Single Cells. Cell Systems (2020) [doi: 10.1016/j.cels.2020.05.001]

8/26/20: Partridge EC et al. Occupancy maps of 208 chromatin-associated proteins in one human cell type. Nature (2020) [doi: 10.1038/s41586-020-2023-4]

8/12/20: Quintero-Cadena P et al. RNA Pol II Length and Disorder Enable Cooperative Scaling of Transcriptional Bursting. Molecular Cell (2020) [doi: 10.1016/j.molcel.2020.05.030]

8/5/20: Fitz J et al. Spt5-mediated enhancer transcription directly couples enhancer activation with physical promoter interaction. Nature Genetics (2020) [doi: 10.1038/s41588-020-0605-6]

7/29/20: Long YC et al. RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells. Nature Genetics (2020) [doi: 10.1038/s41588-020-0662-x]

7/22/20: Ramaker RC et al. Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations. Genome Research (2020) [doi: 10.1101/gr.260463.119]

7/15/20: Wheat JC et al. Single-molecule imaging of transcription dynamics in somatic stem cells. Nature (2020) [doi: 10.1038/s41586-020-2432-4]

7/1/20: Jost M et al. Titrating gene expression using libraries of systematically attenuated CRISPR guide RNAs. Nature Biotechnology (2020) [doi: 10.1038/s41587-019-0387-5]

6/24/20: Fulco CP et al. Activity-by-contact model of enhancer-promoter regulation from thousands of CRISPR perturbations. Nature Genetics (2019) [doi: 10.1038/s41588-019-0538-0]

6/17/20: Tsujimura T et al. Controlling gene activation by enhancers through a drug-inducible topological insulator. eLife (2020) [doi: 10.7554/eLife.47980]

5/27/20: Anderson C et al. Natural variation in stochastic photoreceptor specification and color preference in Drosophila. eLife (2017) [doi: 10.7554/eLife.29593]

5/20/20: Bialek W et al. Action at a distance in transcriptional regulation. arΧiv Preprint (2019) [doi: 10.48550/arXiv.1912.08579]

5/13/20: Slobodin B et al. Transcription Dynamics Regulate Poly(A) Tails and Expression of the RNA Degradation Machinery to Balance mRNA Levels. Molecular Cell (2020) [doi: 10.1016/j.molcel.2020.03.022]

5/6/20: Poramba-Liyanage DW et al. Inhibition of transcription leads to rewiring of locus-specific chromatin proteomes. Genome Research (2020) [doi: 10.1101/gr.256255.119]

4/15/20: Hackett SR et al. Learning causal networks using inducible transcription factors and transcriptome-wide time series. Molecular Systems Biology (2020) [doi: 10.15252/msb.20199174]

4/8/20: Chen J et al. Pervasive functional translation of noncanonical human open reading frames. Science (2020) [doi: 10.1126/science.aay0262]

4/1/20: Yokoshi M et al. Visualizing the Role of Boundary Elements in Enhancer-Promoter Communication. Molecular Cell (2020) [doi: 10.1016/j.molcel.2020.02.007]

3/4/20: Palii CG et al. Single-Cell Proteomics Reveal that Quantitative Changes in Co-expressed Lineage-Specific Transcription Factors Determine Cell Fate. Cell Stem Cell (2019) [doi: 10.1016/j.stem.2019.02.006]

2/19/20: Hendy O et al. Differential context-specific impact of individual core promoter elements on transcriptional dynamics. Molecular Biology Of The Cell (2017) [doi: 10.1091/mbc.E17-06-0408]

2/5/20: Shi Z et al. Heterogeneous Ribosomes Preferentially Translate Distinct Subpools of mRNAs Genome-wide. Molecular Cell (2017) [doi: 10.1016/j.molcel.2017.05.021]

1/29/20: Davidson IF et al. DNA loop extrusion by human cohesin. Science (2019) [doi: 10.1126/science.aaz3418]

1/22/20: McFaline-Figueroa JL et al. A pooled single-cell genetic screen identifies regulatory checkpoints in the continuum of the epithelial-to-mesenchymal transition. Nature Genetics (2019) [doi: 10.1038/s41588-019-0489-5]

1/15/20: Feldman D et al. Optical Pooled Screens in Human Cells. Cell (2019) [doi: 10.1016/j.cell.2019.09.016]

12/11/19: Gibson BA et al. Organization of Chromatin by Intrinsic and Regulated Phase Separation. Cell (2019) [doi: 10.1016/j.cell.2019.08.037]

12/4/19: Viets K et al. Characterization of Button Loci that Promote Homologous Chromosome Pairing and Cell-Type-Specific Interchromosomal Gene Regulation. Developmental Cell (2019) [doi: 10.1016/j.devcel.2019.09.007]

11/20/19: Bartman CR et al. Transcriptional Burst Initiation and Polymerase Pause Release Are Key Control Points of Transcriptional Regulation. Molecular Cell (2019) [doi: 10.1016/j.molcel.2018.11.004]

11/13/19: Lord ND et al. Stochastic antagonism between two proteins governs a bacterial cell fate switch. Science (2019) [doi: 10.1126/science.aaw4506]

11/6/19: Huertas J et al. Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding. Biophysical Journal (2020) [doi: 10.1016/j.bpj.2019.12.038]

10/2/19: Lim B et al. Visualization of Transvection in Living Drosophila Embryos. Molecular Cell (2018) [doi: 10.1016/j.molcel.2018.02.029]

9/25/19: Benabdallah NS et al. Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation. Molecular Cell (2019) [doi: 10.1016/j.molcel.2019.07.038]

8/28/19: Tsai A et al. Multi-enhancer transcriptional hubs confer phenotypic robustness. eLife (2019) [doi: 10.7554/eLife.45325]

8/21/19: Jin Y et al. The Ground State and Evolution of Promoter Region Directionality. Cell (2017) [doi: 10.1016/j.cell.2017.07.006]

8/7/19: Wilson MD et al. Species-specific transcription in mice carrying human chromosome 21. Science (2008) [doi: 10.1126/science.1160930]

7/31/19: Ghavi-Helm Y et al. Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression. Nature Genetics (2019) [doi: 10.1038/s41588-019-0462-3]

7/17/19: Schmiedel JM, Lehner B Determining protein structures using deep mutagenesis. Nature Genetics (2019) [doi: 10.1038/s41588-019-0431-x]

7/10/19: Falk M et al. Heterochromatin drives compartmentalization of inverted and conventional nuclei. Nature (2019) [doi: 10.1038/s41586-019-1275-3]

7/3/19: Paliou C et al. Preformed chromatin topology assists transcriptional robustness of Shh during limb development. PNAS (2019) [doi: 10.1073/pnas.1900672116]

6/19/19: Haberle V et al. Transcriptional cofactors display specificity for distinct types of core promoters. Nature (2019) [doi: 10.1038/s41586-019-1210-7]

6/12/19: McSwiggen DT et al. Evidence for DNA-mediated nuclear compartmentalization distinct from phase separation. eLife (2019) [doi: 10.7554/eLife.47098]

5/29/19: Yamada S et al. The Drosophila Pioneer Factor Zelda Modulates the Nuclear Microenvironment of a Dorsal Target Enhancer to Potentiate Transcriptional Output. Current Biology (2019) [doi: 10.1016/j.cub.2019.03.019]

5/22/19: Bashor CJ et al. Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies. Science (2019) [doi: 10.1126/science.aau8287]

7/18/18: Nicolas D et al. Modulation of transcriptional burst frequency by histone acetylation. PNAS (2018) [doi: 10.1073/pnas.1722330115]

6/28/18: Recillas-Targa F et al. Position-effect protection and enhancer blocking by the chicken beta-globin insulator are separable activities. PNAS (2002) [doi: 10.1073/pnas.102179399]

6/20/18: Diss G, Lehner B The genetic landscape of a physical interaction. eLife (2018) [doi: 10.7554/eLife.32472]

6/13/18: Shen N et al. Divergence in DNA Specificity among Paralogous Transcription Factors Contributes to Their Differential In Vivo Binding. Cell Systems (2018) [doi: 10.1016/j.cels.2018.02.009]

6/6/18: Osterwalder M et al. Enhancer redundancy provides phenotypic robustness in mammalian development. Nature (2018) [doi: 10.1038/nature25461]

5/9/18: Moretto F et al. A regulatory circuit of two lncRNAs and a master regulator directs cell fate in yeast. Nature Communications (2018) [doi: 10.1038/s41467-018-03213-z]

5/2/18: Batut PJ, Gingeras TR Conserved noncoding transcription and core promoter regulatory code in early Drosophila development. eLife (2017) [doi: 10.7554/eLife.29005]

4/25/18: Ren G et al. CTCF-Mediated Enhancer-Promoter Interaction Is a Critical Regulator of Cell-to-Cell Variation of Gene Expression. Molecular Cell (2017) [doi: 10.1016/j.molcel.2017.08.026]

1/31/18: Corrales M et al. Clustering of Drosophila housekeeping promoters facilitates their expression. Genome Research (2017) [doi: 10.1101/gr.211433.116]

1/24/18: Jiang SY et al. Dissecting Nucleosome Function with a Comprehensive Histone H2A and H2B Mutant Library. G3-Genes Genomes Genetics (2017) [doi: 10.1534/g3.117.300252]

12/13/17: Ye ZQ et al. Genome-wide analysis reveals positional-nucleosome-oriented binding pattern of pioneer factor FOXA1. Nucleic Acids Research (2016) [doi: 10.1093/nar/gkw659]

2/10/16: Burrows CK et al. Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs. PLOS Genetics (2016) [doi: 10.1371/journal.pgen.1005793]

2/3/16: Sorrells TR et al. Intersecting transcription networks constrain gene regulatory evolution. Nature (2015) [doi: 10.1038/nature14613]

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\ No newline at end of file diff --git a/journal-club/journal_club_papers.csv b/journal-club/journal_club_papers.csv new file mode 100644 index 0000000..55cd1ca --- /dev/null +++ b/journal-club/journal_club_papers.csv @@ -0,0 +1,149 @@ +date_discussed,title,authors,journal,publication_year,doi +1/3/24,"Ultra-long-range interactions between active regulatory elements",Elias T.F et al.,Genome Research,2023,10.1101/gr.277567.122 +12/20/23,"RNA polymerase II dynamics and mRNA stability feedback scale mRNA amounts with cell size",Matthew P.S et al.,Cell,2023,10.1016/j.cell.2023.10.012 +12/13/23,"Genome-wide measurement of RNA dissociation from chromatin classifies transcripts by their dynamics and reveals rapid dissociation of enhancer lncRNAs",Evgenia N et al.,Cell Systems,2023,10.1016/j.cels.2023.09.005 +12/6/23,"High-throughput characterization of the role of non-B DNA motifs on promoter function",Ilias G-S et al.,Cell Genomics,2022,10.1016/j.xgen.2022.100111 +11/29/23,"An encyclopedia 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Nexus,2023,10.1093/pnasnexus/pgac252 +9/13/23,"Transcription factors interact with RNA to regulate genes",Oksuz O et al.,Molecular Cell,2023,10.1016/j.molcel.2023.06.012 +9/6/23,"Widespread regulatory specificities between transcriptional co-repressors and enhancers in Drosophila",Jacobs J et al.,Science,2023,10.1126/science.adf6149 +8/30/23,"Diverse clonal fates emerge upon drug treatment of homogeneous cancer cells",Goyal Y et al.,Nature,2023,10.1038/s41586-023-06342-8 +8/23/23,"Different chromatin-scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2",Jonathan L et al.,Cell Reports,2023,10.1016/j.celrep.2023.112748 +8/2/23,"Light-activated macromolecular phase separation modulates transcription by reconfiguring chromatin interactions",Yoon JK et al.,Science Advances,2023,10.1126/sciadv.adg1123 +7/26/23,"Temperature-dependent RNA editing in octopus extensively recodes the neural proteome",Matthew AB et al.,Cell,2023,10.1016/j.cell.2023.05.004 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level/s identifies features underlying dosage sensitivity",Naqvi S et al.,Nature Genetics,2023,10.1038/s41588-023-01366-2 +3/15/23,"Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer",Kim YJ et al.,eLife,2022,10.7554/eLife.73395 +3/8/23,"Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness",Chakraborty S et al.,Nature Genetics,2023,10.1038/s41588-022-01295-6 +2/22/23,"Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer’s disease-specific cis-regulatory elements",Anderson AG et al.,Cell Genomics,2023,10.1016/j.xgen.2023.100263 +2/15/23,"A noncoding single-nucleotide polymorphism at 8q24 drives IDH1-mutant glioma formation",Yanchus C et al.,Science,2022,10.1126/science.abj2890 +1/25/23,"Nodal signaling establishes a competency window for stochastic cell fate switching",Economou A et al.,Developmental Cell,2022,10.1016/j.devcel.2022.11.008 +1/11/23,"Enhancer–promoter interactions and transcription are largely maintained upon acute loss of CTCF, cohesin, WAPL or YY1",Hsieh TS et al.,Nature Genetics,2022,10.1038/s41588-022-01223-8 +1/4/23,"Decoding CAR T cell phenotype using combinatorial signaling motif libraries and machine learning",Daniels KG et al.,Science,2022,10.1126/science.abq0225 +12/22/22,"Multiplex profiling of developmental enhancers with quantitative, single-cell expression reporters",Lalanne JB et al.,bioRxiv,2022,10.1101/2022.12.10.519236 +11/9/22,"A mechanism for oxidative damage repair at gene regulatory elements",Ray et al.,Nature,2022,10.1038/s41586-022-05217-8 +11/2/22,"Sequence-dependent surface condensation of a pioneer transcription factor on DNA",Morin et al.,Nature Physics,2022,10.1038/s41567-021-01462-2 +10/5/22,"Hijacking of transcriptional condensates by endogenous retroviruses",Asimi V et al.,Nature Genetics,2022,10.1038/s41588-022-01132-w 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Cell,2019,10.1016/j.molcel.2018.11.004 +11/13/19,Stochastic antagonism between two proteins governs a bacterial cell fate switch,Lord ND et al.,Science,2019,10.1126/science.aaw4506 +11/6/19,Nucleosomal DNA Dynamics Mediate Oct4 Pioneer Factor Binding,Huertas J et al.,Biophysical Journal,2020,10.1016/j.bpj.2019.12.038 +10/2/19,Visualization of Transvection in Living Drosophila Embryos,Lim B et al.,Molecular Cell,2018,10.1016/j.molcel.2018.02.029 +9/25/19,Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation,Benabdallah NS et al.,Molecular Cell,2019,10.1016/j.molcel.2019.07.038 +8/28/19,Multi-enhancer transcriptional hubs confer phenotypic robustness,Tsai A et al.,eLife,2019,10.7554/eLife.45325 +8/21/19,The Ground State and Evolution of Promoter Region Directionality,Jin Y et al.,Cell,2017,10.1016/j.cell.2017.07.006 +8/7/19,Species-specific transcription in mice carrying human chromosome 21,Wilson MD et al.,Science,2008,10.1126/science.1160930 +7/31/19,Highly rearranged 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Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs",Burrows CK et al.,PLOS Genetics,2016,10.1371/journal.pgen.1005793 +2/3/16,Intersecting transcription networks constrain gene regulatory evolution,Sorrells TR et al.,Nature,2015,10.1038/nature14613 +1/27/16,Digital signaling decouples activation probability and population heterogeneity,Kellogg RA et al.,eLife,2015,10.7554/eLife.08931 +1/20/16,Competition between binding sites determines gene expression at low transcription factor concentrations,van Dijk D et al.,bioRχiv Preprint,2016,10.1101/033753 +12/16/15,DNA-dependent formation of transcription factor pairs alters their binding specificity,Jolma A et al.,Nature,2015,10.1038/nature15518 +12/9/15,Transcriptional regulators form diverse groups with context-dependent regulatory functions,Stampfel G et al.,Nature,2015,10.1038/nature15545 diff --git a/main.css b/main.css new file mode 100644 index 0000000..887c56b --- /dev/null +++ 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solid #707070}.gallery img{background:repeating-linear-gradient(45deg, #131313, #131313 4px, #0d0d0d 4px, #0d0d0d 8px)}#lightbox{background:repeating-linear-gradient(45deg, #131313, #131313 4px, #0d0d0d 4px, #0d0d0d 8px)}hr{border-bottom-color:#707070}} \ No newline at end of file diff --git a/people/alumni.csv b/people/alumni.csv new file mode 100644 index 0000000..8d7a801 --- /dev/null +++ b/people/alumni.csv @@ -0,0 +1,33 @@ +name,role,url,photo +Avi Ramu,Graduate Student,https://verily.com/,avi.jpg +Brett Maricque,Graduate Student,https://www.genome.wustl.edu/people/brett-maricque/,brett.jpg +Chris Fiore,Graduate Student,,chris.jpg +Christina Chen,Graduate Student,,christina.jpg +Clarice Hong,Graduate Student,https://www.ashansenlab.com/team.html,clarice.jpg +Dana King,Graduate Student,https://brcf.medicine.umich.edu/staff-member/dana-king-ph-d/,dana.jpg +Desikan,Technician,,desikan.jpg +Devjanee Swain-Lenz,Staff Scientist,,devjanee.jpg +Dustin Baldridge,Assistant Professor,https://dustinbaldridgelab.wustl.edu/,dustin.jpg +Eddie Ramirez,Postbaccalaureate Student,,eddie.jpg +Hemangi Chaudhari,Graduate Student,,hemangi.jpg +Ilaria Mogno,Postdoctoral Fellow,https://icahn.mssm.edu/profiles/ilaria-mogno,ilaria.jpg +Jamie Kwasnieski,Graduate Student,https://www.dynotx.com/team/,jamie.jpg +Jason Gertz,Graduate Student,https://uofuhealth.utah.edu/huntsman/labs/gertz/,jay.jpg +Jeff Hansen,Graduate Student (MSTP),https://mstp.wustl.edu/students/Pages/student_bio.aspx?SID=7260,jeff.jpg +Josh Witten,Graduate Student,https://www.scgssm.org/faculty-staff/dr-josh-witten,josh.jpg +Justin Gerke,Graduate Student,,justin.jpg +Kai Loell,Graduate Student,https://kinneylab.labsites.cshl.edu/people/,kai.jpg +Kimberly Lorenz,Graduate Student,,kim.jpg +Lauren Chircus,Undergraduate Student,,lauren.jpg +Linda Riles,Volunteer,,linda.jpg +Marc Sherman,Graduate Student (MSTP),https://connects.catalyst.harvard.edu/Profiles/display/Person/149030,marc.jpg +Margie Andersohn,Administrative Assistant,,margie.jpg +Max Staller,Postdoctoral Fellow,https://www.stallerlab.com/,max.jpg +Mike Grupe,Technician,,mikeg.jpg +Nicole Rockweiler,Graduate Student,https://mccarrolllab.org/people/,nicole.jpg +Priya Sudarsanam,Senior Scientist,,priya.jpg +Robert Zeigler,Graduate Student,,robert.jpg +Ryan Friedman,Graduate Student,https://cole-trapnell-lab.github.io/team/,ryan.jpg +Sara Lichtarge,Undergraduate Student,,sara.jpg +Shoshana Goldberg,Summer Student,,shoshanna.jpg +Siqi Zhao,Graduate Student,,siqi.jpg \ No newline at end of file diff --git a/people/current.csv b/people/current.csv new file mode 100644 index 0000000..a3a8db5 --- /dev/null +++ b/people/current.csv @@ -0,0 +1,11 @@ +name,role,url,photo +Barak Cohen,Alvin Goldfarb Distinguished Professor of Computational Biology,http://genetics.wustl.edu/staff-members/barak-cohen/,barak.jpg +Mike White,Associate Professor,http://genetics.wustl.edu/mwhite/,mikew.jpg +Yuning Zhang,Postdoctoral Fellow,,yuning.jpg +James Shepherdson,Graduate Student (MSTP),https://mstp.wustl.edu/people/james-shepherdson/,james.jpg +Yawei Wu,Graduate Student,https://dbbs.wustl.edu/people/yawei-wu/,yawei.jpg +Emma Bartley-Dier,Graduate Student,https://dbbs.wustl.edu/people/emma-bartley-dier/,emma.jpg +Jiayu Huang,Masters Student,,jiayu.jpg +Jie Li,Technician,,jie.jpg +Daniel Lyon,Postbaccalaureate Student,,daniel.jpg +Zara Shariff,Undergraduate Student,,zara.jpg \ No newline at end of file diff --git a/people/index.html b/people/index.html new file mode 100644 index 0000000..a7e3601 --- /dev/null +++ b/people/index.html @@ -0,0 +1 @@ +Cohen Lab/People

Cohen Lab

People

Current

Barak Cohen
Alvin Goldfarb Distinguished Professor of Computational Biology
Mike White
Associate Professor
Yuning Zhang
Postdoctoral Fellow
James Shepherdson
Graduate Student (MSTP)
Yawei Wu
Graduate Student
Emma Bartley-Dier
Graduate Student
Jiayu Huang
Masters Student
Jie Li
Technician
Daniel Lyon
Postbaccalaureate Student
Zara Shariff
Undergraduate Student

Alumni

Avi Ramu
Graduate Student
Brett Maricque
Graduate Student
Chris Fiore
Graduate Student
Christina Chen
Graduate Student
Clarice Hong
Graduate Student
Dana King
Graduate Student
Desikan
Technician
Devjanee Swain-Lenz
Staff Scientist
Dustin Baldridge
Assistant Professor
Eddie Ramirez
Postbaccalaureate Student
Hemangi Chaudhari
Graduate Student
Ilaria Mogno
Postdoctoral Fellow
Jamie Kwasnieski
Graduate Student
Jason Gertz
Graduate Student
Jeff Hansen
Graduate Student (MSTP)
Josh Witten
Graduate Student
Justin Gerke
Graduate Student
Kai Loell
Graduate Student
Kimberly Lorenz
Graduate Student
Lauren Chircus
Undergraduate Student
Linda Riles
Volunteer
Marc Sherman
Graduate Student (MSTP)
Margie Andersohn
Administrative Assistant
Max Staller
Postdoctoral Fellow
Mike Grupe
Technician
Nicole Rockweiler
Graduate Student
Priya Sudarsanam
Senior Scientist
Robert Zeigler
Graduate Student
Ryan Friedman
Graduate Student
Sara Lichtarge
Undergraduate Student
Shoshana Goldberg
Summer Student
Siqi Zhao
Graduate Student

Lab Photos

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a/posts/asbmb-meeting/IMG2_YaweiPoster.jpg b/posts/asbmb-meeting/IMG2_YaweiPoster.jpg new file mode 100644 index 0000000..dca49c3 Binary files /dev/null and b/posts/asbmb-meeting/IMG2_YaweiPoster.jpg differ diff --git a/posts/asbmb-meeting/IMG3_ClariceTalk.jpg b/posts/asbmb-meeting/IMG3_ClariceTalk.jpg new file mode 100644 index 0000000..56e20a5 Binary files /dev/null and b/posts/asbmb-meeting/IMG3_ClariceTalk.jpg differ diff --git a/posts/asbmb-meeting/IMG4_YaweiAward.jpg b/posts/asbmb-meeting/IMG4_YaweiAward.jpg new file mode 100644 index 0000000..52c1a75 Binary files /dev/null and b/posts/asbmb-meeting/IMG4_YaweiAward.jpg differ diff --git a/posts/asbmb-meeting/index.html b/posts/asbmb-meeting/index.html new file mode 100644 index 0000000..3be5f52 --- /dev/null +++ b/posts/asbmb-meeting/index.html @@ -0,0 +1 @@ +Cohen Lab/Posts/Cohen Lab attends ASBMB meeting

Cohen Lab

Cohen Lab attends ASBMB meeting

Mike, Clarice, Ryan, Kai, and Yawei recently traveled to the Stowers Institute in Kansas City to attend the ASBMB conference "Evolution and Core Processes in Gene Expresson". Clarice gave a talk and everyone else presented a poster. Congratulations to Yawei, who was awarded a Best Poster Award for a graduate student!

We had a great time learning about the latest research in cis-regulatory grammar, enhancer evolution, and predictive models of gene regulation. We also enjoyed eating some delicious Kansas City BBQ and connecting with our peers and colleagues in the field.

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Cohen Lab

Congratulations Avi!

The second of three in this week's Cohen lab defense-o-rama — congratulations to Avi Ramu for successfully defending his thesis, "Sources and consequences of cell-to-cell variability in gene expression"! Watch a recording of the defense here.


Attachments

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Cohen Lab

O lentivirus – Lab Meeting 03/11/21

O lentivirus,
Will you please make more cells green,
Wonder what I’ll find.

Credit – Avinash Ramu

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Cohen Lab

Back to back to back!

Congratulations to Clarice, to Siqi, and to Jeff on successfully proposing their theses! The three have hitched their wagons together so as one wagon advances ahead, the others are pulled alongside. In such a way, the three have boosted each other’s science and buoyed each other’s spirits. A regular Cerberus of science. What a team!

We look forward to seeing what comes out of each one’s thesis work.

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Cohen Lab

AI Art Gallery in Barak's Office

When the PI is away, the grad students play!

Every year when Barak goes out of town for a long time, we prank his office as a welcome back surprise. Barak has recently taken a strong interest in Paul Cezanne, so this year we turned his office into an art gallery. We used the AI DALL-E 2 to generate fake art and hung it next to real art. We used another AI called ChatGPT to generate fake museum labels to accompany the fake art.

In addition, James used 24 photos of Barak from over the years and the "Dreambooth" technique to teach another AI, Stable Diffusion, what Barak looks like. Then, James asked Stable Diffusion to generate portraits of Barak in the style of several different artists. The collection of portraits is truly stunning -- there's even a museum label from ChatGPT emphasizing the mystery of the portraits' recurring subject!

Here are some pictures of the decor. Can you tell which pieces are real works of art?

Below is what ChatGPT had to say about the portrait collection:

"The Many Faces of _______: A Portrait Collection"

This collection features a series of portrait paintings, all depicting the same individual. The artwork on display was created by a diverse group of artists, each bringing their own unique style and perspective to the portrayed subject.

Who was this person, and why were they painted by so many different artists? These paintings offer a glimpse into the life and personality of the subject, but leave much to the imagination.

From the traditional techniques of the Old Masters, to the bold brushstrokes and vibrant colors of modern art, this collection showcases the versatility and enduring appeal of portraiture. The subjects depicted range from formal poses in elegant attire, to more relaxed and casual depictions.

Despite the varied styles and approaches, each of these paintings captures the essence of the subject and conveys a sense of their personality. This collection serves as a testament to the enduring power of portraiture as a means of preserving the human spirit on canvas, and leaves us wondering about the mystery of the person depicted.

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Cohen Lab

The student – Lab meeting 01/21/21

The student, she felt some distress,
That the QE could end up a mess.
She thought there’d be questions aplenty.
But the Profs’ heads were actually empty,
And the exam was a smashing success!

Credit – Barak Cohen

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Cohen Lab

A TF ponders – Lab meeting 08/27/20

On the sense strand a TF pondered,
“Which way to the enhancer I wonder?”
Should I follow the loop,
through this phase separate soup?
Or hitch a ride with my pal p300?

Credit – Barak Cohen

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Cohen Lab

Listen to Barak’s Podcast with Shelina!

You can listen to the podcast here.

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Cohen Lab

Big Ideas Night

The inaugural Cohen Lab Big Ideas Night! Barak loves to tell the story of the discovery of transfer RNA. Our scientific forefathers kicked around ideas over tea, scones, and maybe some beers too. Through this sort of brainstorming, the idea that there must be some molecule shuttling around amino acids was borne. Once our forefathers convinced themselves of the specifics of the idea, and how the experiment would work, actually conducting it became trivial. And thus tRNA was discovered. If such great biological discovery can be made over scones and ales, then lets indulge!

Settled into our lab’s old haunts, The Scottish Arms, we bounced around big ideas focused on master regulators. With new graduate students patrolling the benches, the lab has taken up new vocabulary as well: pioneer factors. Discussion flitted between definition, mechanism, and proof of these special transcription factors; perhaps we leave this discussion for our graduate students’ future presentations.

And so big idea #1 was not as much an idea but an open question: what would result from treating cells with two different master regulator cocktails? What type of cell would the transcriptome resemble? Would we see a random assortment of cell A and cell B, or would we see a monster, with the head of cell A and the body of cell B? With Halloween on the horizon, we’ll incubate this spooky idea until a rainy day comes along, ripe with time for a big idea experiment.

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Cohen Lab

Big Ideas Night

Following the smashing success of our first big ideas night, big ideas coated our benches just as Barak’s wool sweater once did. Ideas so big that we contemplated moving into a building with even higher ceilings. But alas, we shan’t desert our loyal coffee maker, so we stay put.

The second gathering of Big Idea’s Night took place at Retreat Gastropub. Amidst some fries and whiskey, we pitched ideas for how we can utilize our Center’s newest sequencing technologies. PacBio’s ultra-long sequencing reads and the 10x single-cell method both provide new avenues for innovative research. And to not exclude our friends in imaging, we discussed a new application of FISH, called clampFISH. This technology generates a FISH signal strong enough to be detected by FACS.

The idea most discussed utilizes ultra-long reads to query chromatin interactions. In our lab, we have identified strong regional effects on gene expression. How far do these regions stretch? With our landing pad in place, we can integrate reporter genes at variable distances and ask how the length relates to the coordinated expression between the reporter gene at the LP and at distance. If we see discordance at a certain distance, it may be possible to restore the similar expression with looping-related proteins, such as CTCF or YY1. As team landing pad ventures further into the mechanisms of this strong regional effect, we will draw from these discussions and this big idea.

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Cohen Lab

Big Ideas Night

Aaaand we’re back for round three. This time with some new faces! Ah, time ticks on and people come and go. Fortunately for us, whiskey and science persist.

Back at the Scottish Arms, we tackled the problem of detecting simultaneous binding of two proteins to DNA; the proteins each must bind to the DNA and thus are not co-localized due to protein-protein interactions. In Barak’s words…imagine the TF a cowboy. Once on its DNA horse, it can lasso other TFs around it, but only those TFs also on horses. A wild west of a genome, indeed.

Some ideas included FRET-seq, 2-dimensional gels, and combination usage of accessibility and binding footprints. Without a clear winner, we’ll wait another day before discarding the lassos hanging from our bench top shelves. Until next time, keep thinking big, you crazy scientists.

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Cohen Lab

Bissinger’s Chocolate Factory Tour

In an effort to find something sweeter than the satisfaction of sequencing DNA, the lab trekked downtown to visit St. Louis’ own Bissinger’s Chocolate Factory. Led by a couple of chocolate fanatics, we sought to uncover the secrets behind this famous chocolate. But alas, our phones were confiscated and the chocolate-factory-dungeon was threatened if we strayed from the walkway and became too pesky of visitors.

On our tour, we learned of the hand-crafted nature of Bissinger’s chocolate. A few lab members couldn’t help but be reminded of how we too take care to make sure that every library we design receives high quality and individualized attention. After the tour, we were treated to a tasting. Barak liked the chocolate-covered cherries. Siqi preferred the milk chocolate over the dark chocolate. Clarice quipped that her mint chocolate tasted like toothpaste.

All in all, we had a wonderful time. Was it sweeter than that feeling of opening up your sequencing results to find a beautiful array of A’s, C’s, T’s and G’s? Maybe not, but alas the factory was neat and the chocolate was tasty.

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Cohen Lab

Brett Maricque, interviewed on “St. Louis on the Air”

Graduate student and current BALSA president, Brett Maricque, and co-founder, Maxim Schillebeeckx, discuss how the BALSA group allows graduate students to gain business experience while providing quality, low cost consulting services for the growing St. Louis biotechnology sector and generating grant money for local entrepreneurs through the BALSA Foundation. Listen to the full conversation on the “St. Louis on the Air” website.

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Cohen Lab

Congratulations Clarice!

Congratulations to Clarice Hong for successfully defending her thesis, "Understanding gene regulation with high-throughput genome-integrated reporter assays"! Watch a recording of her defense here.

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Cohen Lab

Brad – Lab Meeting 10/15/20

There once was a promoter called Brad
Who flew to a landing pad
He left in style
But landed in hell
He makes me a little mad

Credit – Clarice Hong

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Cohen Lab

Insulator – Lab meeting 04/01/2021

It hides in black and dark genomic space
Though with enhancers it must intervene
And once called junk by many in old days
It found fame in the chicken globin gene.
The saw cHS4 had magic game
The researchers who found it thus cried out
O insulator thou art not the same
Now with you loops will never be in doubt.
But then one day a graduate student thought
I wonder how you’ll fare in landing pads
Alas her efforts always came to naught
Much time was wasted chasing it in labs.
But stay, be patient, one day you will see
It will be fucking understood by me.

Credit – Clarice Hong

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Cohen Lab

Donut Day in the Cohen Lab

Mary Poppins sang that a spoonful of sugar helps the medicine go down. This morning, we sang that a dozen John’s donuts helps the Washington University in St. Louis Institutional Biological & Chemical Safety Committee Protocol go down, and an additional spoonful of sugar helps that lengthy name go down.

Around the rooster’s crow, Barak, Max, Clarice, and Jeff gathered round a table piled high with past protocols, laptops, safety certificates, and a hearty collective knowledge ranging from the origins of reporter genes to the dangers of graphite in space. And then there were the donuts. Our lab has a storied tradition of sweetening unpleasant days with samplings of St. Louis’ fabulous donut scene. For RNA extractions, we grab a dozen from World’s Fair. For library preparation, we grab a dozen from Vincent Van Doughnut. For Clarice’s seven-hour-long marathon of a practice talk, we grab a dozen from Strange. And for the latest effort in maintaining a safe and accountable lab, we grab a dozen from John’s.

Perched next to our venerable coffee source, the four toiled as the sun progressed across the sky. Time’s passing was marked only by the regular flow of fellow scientists, coming to refill their receptacles with the dark brown life fuel that surely represents far too high of a proportion within our electrolyte-deficient bloodstream. Some offered sympathies, while others jealously eyed the donuts. The latter group hoped to only experience the sweet without the accompanying sour.

As the crescent moon rose on the horizon, the protocol neared complete. The four, splitting the final donut into quarters, each raised a piece in cheers to renewed safety and accountability. And quickly retired from lab to find some vegetables.

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Cohen Lab

Zoom – Lab Meeting 11/19/2020

Your face frozen on
my screen. These days we all have
limited bandwidth.

haiku by Janni Lee Simner, shared by Dustin

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Cohen Lab

Farewell, Hemangi!

On Sunday, Barak hosted a farewell brunch for our senior graduate student, Hemangi Chaudhari. Beyond her contributions to the scientific community, Hemangi has provided wisdom and guidance to our lab for several years now. To the younger graduates, she provided patient instruction. To her classmates, she provided unbeatable cuisine and loyal companionship. And to post-docs and PIs, she provided an intellectual debate over the implications of a result or the design of an experiment.

As Hemangi moves to Boston, we wish her the warmest farewell. As she leaves behind her pipettes (to be scrounged after by incoming students) she leaves a lasting mark on both the lab and the scientific trajectories of those that were lucky enough to spend time with her in St. Louis. We all hope to cross paths again soon, as we crisscross through scientific communities all pointed towards a greater understanding of biology. While the farewells may be blue, the difficulty in parting demonstrates how strong the connections developed to be.

Farewell, Hemangi! We’ll see you again soon!

Image: Masala dosa – featured at the farewell brunch – every bite cherished (source: NY Times).

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Cohen Lab

First Cohen Research Conference

The first-ever Cohen Research Conference was held Feb 25-27, 2020 at Stonehaven Castle, Eureka Springs, AR. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board-games, day-time and night-time hikes, a meditation session, sciencing around a campfire, spotting constellations on a clear black sky, balancing the entire lab on a log, and impromptu midnight performances with the guitar by Barak. It was a truly special experience. Thanks to Clarice and Jeff, the chief organizers of the conference.

Photo credit: James

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Cohen Lab

Fourth Cohen Research Conference

The fourth annual Cohen Research Conference was held October 23-25, 2023 in Michigan City, IN. Lab members presented talks on big ideas or out-there experiments. Continuing the tradition from prior CRCs, we also enjoyed communal cooking, a campfire near the lake, and a dunes hike in Indiana Dunes National Park which passed through Cowles Bog, a site of seminal research on ecological succession!

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Cohen Lab

Summer Cookout — Goodbye, Jeff and Siqi!

The lab joined family and friends to celebrate Jeff and Siqi's successful defenses with a backyard cookout! Barak presented a book to each of the graduates, and everyone was treated to a magic show … um, I mean scientific demonstration of the power of ESP.

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Cohen Lab

One last thing before I go – 01/28/2020

chose artist’s home, for
science is self expression.
found beauty in truth.

This was Max’s last lab meeting with us. Max also shared some words of wisdom with us.

Words of Wisdom

  • Mentoring matters
  • Teaching will make you a better researcher and research will make you a better teacher
  • The goal of the lab is to help lab members get to where they want to go
  • Love people for their strengths and support them through their weaknesses
  • Science is a form of self expression
  • Trust your esthetic taste in problems and answers.
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Cohen Lab

Goodbye Ryan, Avi, and Kai!

The lab met at Barak's house to congratulate Ryan, Avi and Kai on their successful thesis defenses and wish them well in their next endeavors! Ryan will be starting a postdoc in Cole Trapnell's lab at UW, Avi will be joining the team at Verily Life Sciences, and Kai will be starting a postdoc in Justin Kinney's lab at CSHL.

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Cohen Lab

Hemangi’s Thesis Defense

Our intrepid landing pad explorer has successfully defended her thesis, titled “Integration of local and regional regulatory information in the human genome”!!!

Afterwards, we toasted champagne and had delicious Himalayan Yeti as we recounted Hemangi’s many wonderful accomplishments.

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Cohen Lab

Posts

Fourth Cohen Research Conference

The fourth annual Cohen Research Conference was held October 23-25, 2023 in Michigan City, IN. Lab members presented talks on big ideas or out-there experiments. Continuing the tradition from prior CRCs, we also enjoyed communal cooking, a campfire near the lake, and a dunes hike in Indiana Dunes National Park which passed through Cowles Bog, a site of seminal research on ecological succession!

Goodbye Ryan, Avi, and Kai!

The lab met at Barak's house to congratulate Ryan, Avi and Kai on their successful thesis defenses and wish them well in their next endeavors! Ryan will be starting a postdoc in Cole Trapnell's lab at UW, Avi will be joining the team at Verily Life Sciences, and Kai will be starting a postdoc in Justin Kinney's lab at CSHL.

Well done, Kai!

Congratulations to Kai Loell for bringing the Cohen lab defense record to 3/3 this week by successfully defending his thesis, "Biophysically-informed models of heterogeneity in transcription factor activity"! Watch a recording of the defense here.


Attachments

Congratulations Avi!

The second of three in this week's Cohen lab defense-o-rama — congratulations to Avi Ramu for successfully defending his thesis, "Sources and consequences of cell-to-cell variability in gene expression"! Watch a recording of the defense here.


Attachments

Congratulations Ryan!

Congratulations to Ryan Friedman for kicking off the Cohen lab's three-defense week by successfully defending his thesis, "Iterative machine learning of a cis-regulatory grammar"! Watch a recording of the defense here.


Attachments

AI Art Gallery in Barak's Office

When the PI is away, the grad students play!

Every year when Barak goes out of town for a long time, we prank his office as a welcome back surprise. Barak has recently taken a strong interest in Paul Cezanne, so this year we turned his office into an art gallery. We used the AI DALL-E 2 to generate fake art and hung it next to real art. We used another AI called ChatGPT to generate fake museum labels to accompany the fake art.

In addition, James used 24 photos of Barak from over the years and the "Dreambooth" technique to teach another AI, Stable Diffusion, what Barak looks like. Then, James asked Stable Diffusion to generate portraits of Barak in the style of several different artists. The collection of portraits is truly stunning -- there's even a museum label from ChatGPT emphasizing the mystery of the portraits' recurring subject!

Here are some pictures of the decor. Can you tell which pieces are real works of art?

Below is what ChatGPT had to say about the portrait collection:

"The Many Faces of _______: A Portrait Collection"

This collection features a series of portrait paintings, all depicting the same individual. The artwork on display was created by a diverse group of artists, each bringing their own unique style and perspective to the portrayed subject.

Who was this person, and why were they painted by so many different artists? These paintings offer a glimpse into the life and personality of the subject, but leave much to the imagination.

From the traditional techniques of the Old Masters, to the bold brushstrokes and vibrant colors of modern art, this collection showcases the versatility and enduring appeal of portraiture. The subjects depicted range from formal poses in elegant attire, to more relaxed and casual depictions.

Despite the varied styles and approaches, each of these paintings captures the essence of the subject and conveys a sense of their personality. This collection serves as a testament to the enduring power of portraiture as a means of preserving the human spirit on canvas, and leaves us wondering about the mystery of the person depicted.

Congratulations Clarice!

Congratulations to Clarice Hong for successfully defending her thesis, "Understanding gene regulation with high-throughput genome-integrated reporter assays"! Watch a recording of her defense here.

Third Cohen Research Conference

The third annual Cohen Research Conference was held October 17-19, 2022 in Cadiz, KY. Everyone presented a talk about big questions or ideas they have. We also enjoyed communal cooking, a campfire near the water, a hike through the Land Between the Lakes National Recreation Area, moonshine tasting, puzzles and board games, guitar performances by Barak and rotation student AJ, and more! We also stopped in Metropolis, IL to see a 15-foot statue of Superman. A great time was had by all. The CRC has certainly been cemented as a lab tradition!

Photo credit: James

New Paper from the Lab

Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats Kai!

Cohen Lab attends ASBMB meeting

Mike, Clarice, Ryan, Kai, and Yawei recently traveled to the Stowers Institute in Kansas City to attend the ASBMB conference "Evolution and Core Processes in Gene Expresson". Clarice gave a talk and everyone else presented a poster. Congratulations to Yawei, who was awarded a Best Poster Award for a graduate student!

We had a great time learning about the latest research in cis-regulatory grammar, enhancer evolution, and predictive models of gene regulation. We also enjoyed eating some delicious Kansas City BBQ and connecting with our peers and colleagues in the field.

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Cohen Lab

James F30 Success

Congrats James for recieving a F30 award from NEI for the project "Multiplex functional assay of variant effect in the retinal transcription factor CRX".

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Cohen Lab

Congratulations Jeff!

Congratulations to Jeff Hansen for a successful defense of his thesis, “A Test of the Pioneer Factor Hypothesis for Silent Gene Activation”. Watch a recording of his defense here. Jeff is an MSTP student and will be returning to the clinic for the final two years of Medical School, so we still hope to see him around!


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Jeff is a transcription factor – Lab meeting 09/24/20

Pursuit

Jeff biked off to find a good beer
But only closed breweries would appear
Good thing he was a pioneer developmental transcription factor
He broke in with his zinc retractor
And drank all the night with good cheer

Credit – Jeff Hansen

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Cohen Lab

Jeff, Bagel, Beer – Lab Meeting 05/27/2021

Jeff
Genome
Genetics
Phonetics
Photon
Roton
Rotor
Motor
Money
Honey
Bunny
Bagel
Kegel
Candy
Dandy
Dandruff
Beard scruff
Beer
Fear
Deer
Donuts

Credit – Jeff Hansen

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Cohen Lab

Spot – Lab meeting 02/11/2021

See Spot run
See Spot scan
See Spot wait for exposing sites
See Spot bind
See Spot take
See Spot outcompete nucleosomes
See Spot spread
See Spot’s friends
See Spot create accessibility
See Spot wave
See Spot call
See Spot recruit transcriptional machinery
See Spot smile
See Spot cheer
See Spot reprogram to a happy lineage
Is Spot weird?
Is Spot cool?
No, Spot is just like all of the other transcription factors!

Credit – Jeff Hansen

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Cohen Lab

New Paper from the Lab

Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats Kai!

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Cohen Lab

Well done, Kai!

Congratulations to Kai Loell for bringing the Cohen lab defense record to 3/3 this week by successfully defending his thesis, "Biophysically-informed models of heterogeneity in transcription factor activity"! Watch a recording of the defense here.


Attachments

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Cell walls don’t crumble – Lab meeting 02/04/2021

Cell walls don’t crumble
DNA’s nowhere to see
Will Fluors light the way?

Credit – Kai Loell

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Cohen Lab

There once were some yeast – Lab Meeting 05/13/2021

There once were some yeast from afar
That simply would not PCR
Boiling, freezing were no use
So they got ground up and juiced
And now show their genetic scars

Credit – Kai Loell

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Marc Sherman receives prestigious Spencer T. and Ann W. Olin Medical Science Fellowship

The Olin Fellowships recognize accomplishments in biomedical research by doctoral students at Washington University. While thirty-two students were nominated, only eight awards were granted. Marc’s research focused on stochasticity in gene expression and the kinds of “noise” that are often disregarded when expression is measured. While he has moved on to his clinical rotations, Marc’s work in the Cohen lab can be found under our publications header.

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Cohen Lab

Max K99 Success

Great work Max for recieving a K99 award from NIGMS for his project "High-Throughput Functional Interrogation Of Mammalian Activation Domains".

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Cohen Lab

Mike White promoted to Assistant Professor

We are pleased to announce the Mike White PhD has been promoted to the rank of Assistant Professor of Genetics. This is well deserved. It is expected that Mike will continue his own research with the added distractions of worrying about grants, sitting on useless committees, and teaching classes to recalcitrant graduate students.

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A puzzle – Lab meeting 03/04/21

Swapping out k-mers
Elements become too active
Small changes puzzle me

Credit – Mike White

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Mike White interviewed in St. Louis Magazine

Our own Mike White talks about what makes genetics cool in an interview for St. Louis magazine.

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Cohen Lab

Mutants, brawn and bereavement from Nicole’s lab meeting – 8/13/20

There once was a zygote conceived
Whose genome mutated with ease
The mutations plopped on
With great strength and brawn
And now the parents are bereaved

Credit – Nicole Rockweiler

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Summer Cookout — Goodbye, Jeff and Siqi!

The lab joined family and friends to celebrate Jeff and Siqi's successful defenses with a backyard cookout! Barak presented a book to each of the graduates, and everyone was treated to a magic show … um, I mean scientific demonstration of the power of ESP.

Congratulations Siqi!

Congratulations to Siqi Zhao for a successful defense of his thesis, “Single-cell massively parallel reporter assays”, completing the Cohen lab June thesis defense double-header! Watch a recording of his defense here!


Attachments

Congratulations Jeff!

Congratulations to Jeff Hansen for a successful defense of his thesis, “A Test of the Pioneer Factor Hypothesis for Silent Gene Activation”. Watch a recording of his defense here. Jeff is an MSTP student and will be returning to the clinic for the final two years of Medical School, so we still hope to see him around!


Attachments

Papers from the lab

Ryan, Max, Clarice and Jeff all had papers published recently! You can find the links to the papers in the Publications section.

Shown above are cool illustrations that describe Clarice's and Jeff's papers. Can you spot the molecular players in these?

James F30 Success

Congrats James for recieving a F30 award from NEI for the project "Multiplex functional assay of variant effect in the retinal transcription factor CRX".

Second Cohen Research Conference

The second Cohen Research Conference was held September 13-15, 2021 at Lake Geneva, WI. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board games, swimming and kayaking, a lakeside hike, a meditation session, science talks out on the deck, and more! A strong continuation of CRC tradition. Thanks to Clarice and Jeff, the chief organizers of the conference.

Jeff, Bagel, Beer – Lab Meeting 05/27/2021

Jeff
Genome
Genetics
Phonetics
Photon
Roton
Rotor
Motor
Money
Honey
Bunny
Bagel
Kegel
Candy
Dandy
Dandruff
Beard scruff
Beer
Fear
Deer
Donuts

Credit – Jeff Hansen

Details kill – Lab meeting 05/20/2021

No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.

Credit – Yawei Wu

There once were some yeast – Lab Meeting 05/13/2021

There once were some yeast from afar
That simply would not PCR
Boiling, freezing were no use
So they got ground up and juiced
And now show their genetic scars

Credit – Kai Loell

Insulator – Lab meeting 04/01/2021

It hides in black and dark genomic space
Though with enhancers it must intervene
And once called junk by many in old days
It found fame in the chicken globin gene.
The saw cHS4 had magic game
The researchers who found it thus cried out
O insulator thou art not the same
Now with you loops will never be in doubt.
But then one day a graduate student thought
I wonder how you’ll fare in landing pads
Alas her efforts always came to naught
Much time was wasted chasing it in labs.
But stay, be patient, one day you will see
It will be fucking understood by me.

Credit – Clarice Hong

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Cohen Lab

Posts

O lentivirus – Lab Meeting 03/11/21

O lentivirus,
Will you please make more cells green,
Wonder what I’ll find.

Credit – Avinash Ramu

A puzzle – Lab meeting 03/04/21

Swapping out k-mers
Elements become too active
Small changes puzzle me

Credit – Mike White

Spot – Lab meeting 02/11/2021

See Spot run
See Spot scan
See Spot wait for exposing sites
See Spot bind
See Spot take
See Spot outcompete nucleosomes
See Spot spread
See Spot’s friends
See Spot create accessibility
See Spot wave
See Spot call
See Spot recruit transcriptional machinery
See Spot smile
See Spot cheer
See Spot reprogram to a happy lineage
Is Spot weird?
Is Spot cool?
No, Spot is just like all of the other transcription factors!

Credit – Jeff Hansen

Cell walls don’t crumble – Lab meeting 02/04/2021

Cell walls don’t crumble
DNA’s nowhere to see
Will Fluors light the way?

Credit – Kai Loell

One last thing before I go – 01/28/2020

chose artist’s home, for
science is self expression.
found beauty in truth.

This was Max’s last lab meeting with us. Max also shared some words of wisdom with us.

Words of Wisdom

  • Mentoring matters
  • Teaching will make you a better researcher and research will make you a better teacher
  • The goal of the lab is to help lab members get to where they want to go
  • Love people for their strengths and support them through their weaknesses
  • Science is a form of self expression
  • Trust your esthetic taste in problems and answers.

The student – Lab meeting 01/21/21

The student, she felt some distress,
That the QE could end up a mess.
She thought there’d be questions aplenty.
But the Profs’ heads were actually empty,
And the exam was a smashing success!

Credit – Barak Cohen

What is this sequence – Lab meeting – 01/14/2021

What is this sequence–
Strong, silent, or inactive?
It’s all in the bits.

Credit – Ryan Friedman

Haiku was here – Lab meeting 12/17/2020

Haiku was here

From ashes of sparks,
Poets pick up left pieces,
“Hey! Poems were here”

Credit – Yawei Wu

If one sings about the invisible, and to Calvino – Lab Meeting 12/03/2020

If one sings about the invisible, and to Calvino
These cities Marco Polo told the Khan,
Which are forgotten by memory now,
Only shadows exist and else are gone.
Oh Where? In Levantine but no one saw.
Ooh! A human cries for joy not for pain,
Only in Diomera with damascened wall;
And Isidora, before her all fain,
In endless desires memory is all.
It’s real? The Great Khan asks, with his back bent.
Does it matter? As light as a feather
Polo’s answer is outside the present,
Just as daydreams, do not wither.
To feel the subtlety of foreverness,
And to kiss the pain of experience.

Credit – Siqi Zhao

Zoom – Lab Meeting 11/19/2020

Your face frozen on
my screen. These days we all have
limited bandwidth.

haiku by Janni Lee Simner, shared by Dustin

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Cohen Lab

Posts

Brad – Lab Meeting 10/15/20

There once was a promoter called Brad
Who flew to a landing pad
He left in style
But landed in hell
He makes me a little mad

Credit – Clarice Hong

Jeff is a transcription factor – Lab meeting 09/24/20

Pursuit

Jeff biked off to find a good beer
But only closed breweries would appear
Good thing he was a pioneer developmental transcription factor
He broke in with his zinc retractor
And drank all the night with good cheer

Credit – Jeff Hansen

A TF ponders – Lab meeting 08/27/20

On the sense strand a TF pondered,
“Which way to the enhancer I wonder?”
Should I follow the loop,
through this phase separate soup?
Or hitch a ride with my pal p300?

Credit – Barak Cohen

Rainbow

Look what our intrepid observer Yawei spotted outside. It seems that stay-at-home won’t stop us from making observations. Imagine that you are the first human to ever observe a rainbow, how would you explain it? Or would you rather just enjoy it?

A computationalist’s lament – Ryan’s lab meeting 8/20/20

Stay home? No problem! My work won’t be quenched.
After all, things in lab can make quite a stench.
But one fifty seven days
of work from home craze
makes me wish I did more at the bench.

Credit – Ryan Friedman

Mutants, brawn and bereavement from Nicole’s lab meeting – 8/13/20

There once was a zygote conceived
Whose genome mutated with ease
The mutations plopped on
With great strength and brawn
And now the parents are bereaved

Credit – Nicole Rockweiler

Gene regulation and fruit from a tree – Yawei’s lab meeting 8/7/20

Yawei started lab meeting with a cartoon depicting a model of gene regulation. See if you can figure out the analogy.

Image credit – Yawei Wu

Haiku – Siqi’s lab meeting 7/30

Of those sleepless nights,
how many did you consume,
stochasticity?

Credit – Siqi Zhao

Congrats Ryan on your F31!

Congrats Ryan for recieving a F31 award from NHGRI ("Interpreting function of non-coding sequences with synthetic biology and machine learning").

Virtual Reunion

The virtual celebration for Dana’s paper turned into a lab Zoom reunion on April 7, 2020. It was great to see everyone who could make it and hear stories from different eras of the lab.

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First Cohen Research Conference

The first-ever Cohen Research Conference was held Feb 25-27, 2020 at Stonehaven Castle, Eureka Springs, AR. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board-games, day-time and night-time hikes, a meditation session, sciencing around a campfire, spotting constellations on a clear black sky, balancing the entire lab on a log, and impromptu midnight performances with the guitar by Barak. It was a truly special experience. Thanks to Clarice and Jeff, the chief organizers of the conference.

Photo credit: James

Sailing fun

The lab spent a fun day sailing on Barak’s boat last week. The weather obliged with some great sunshine and good winds. The rejuvenated crew are now back in the lab to tackle smaller amounts of liquid.

Photo credit: James

Max K99 Success

Great work Max for recieving a K99 award from NIGMS for his project "High-Throughput Functional Interrogation Of Mammalian Activation Domains".

We do science, too

We have a lot of fun in the Cohen Lab. We sail, and we eat donuts, and we brainstorm big ideas over tasty cocktails. But at core, we are a band of renegades, uncovering secrets of the genome. The only evidence for that claim that you’ll need is the picture below, showing Max and Maria and Clarice taking care of their cells, on a Cohen-Triple-TC-Hood-Combo-Day.

Back to back to back!

Congratulations to Clarice, to Siqi, and to Jeff on successfully proposing their theses! The three have hitched their wagons together so as one wagon advances ahead, the others are pulled alongside. In such a way, the three have boosted each other’s science and buoyed each other’s spirits. A regular Cerberus of science. What a team!

We look forward to seeing what comes out of each one’s thesis work.

Sailing through graduate school

When a few Cohen Lab members found themselves listlessly floating through the doldrums of graduate school, Barak came to the rescue. Quickly navigating rivers and creeks and roadside puddles, he sailed across Illinois and arrived in lab to the shock and awe of the other landlubber labs. His new crew gave a quick “yippee” and climbed aboard.

Might there be merits to guiding the ship into international waters where the rogue scientists could set up a nautical lab? Benefits would include easy access to fresh seafood, plenty of salt water for buffering our enzymatic reactions, and the inspiration of the fresh sea breeze. That said, we may need to invent new nautical approaches to sequencing DNA, discover internet-free ways of reading new papers, and identify some Atlantis-based funding source.

For now, we’ll keep residence within our lovely coffee-laden abode and escape to Carlyle Lake when the siren song becomes too much. But when the floods arrive again, look to the Cohen Lab for the beginnings of the NNIH: the National Nautical Institutes of Health.

Donut Day in the Cohen Lab

Mary Poppins sang that a spoonful of sugar helps the medicine go down. This morning, we sang that a dozen John’s donuts helps the Washington University in St. Louis Institutional Biological & Chemical Safety Committee Protocol go down, and an additional spoonful of sugar helps that lengthy name go down.

Around the rooster’s crow, Barak, Max, Clarice, and Jeff gathered round a table piled high with past protocols, laptops, safety certificates, and a hearty collective knowledge ranging from the origins of reporter genes to the dangers of graphite in space. And then there were the donuts. Our lab has a storied tradition of sweetening unpleasant days with samplings of St. Louis’ fabulous donut scene. For RNA extractions, we grab a dozen from World’s Fair. For library preparation, we grab a dozen from Vincent Van Doughnut. For Clarice’s seven-hour-long marathon of a practice talk, we grab a dozen from Strange. And for the latest effort in maintaining a safe and accountable lab, we grab a dozen from John’s.

Perched next to our venerable coffee source, the four toiled as the sun progressed across the sky. Time’s passing was marked only by the regular flow of fellow scientists, coming to refill their receptacles with the dark brown life fuel that surely represents far too high of a proportion within our electrolyte-deficient bloodstream. Some offered sympathies, while others jealously eyed the donuts. The latter group hoped to only experience the sweet without the accompanying sour.

As the crescent moon rose on the horizon, the protocol neared complete. The four, splitting the final donut into quarters, each raised a piece in cheers to renewed safety and accountability. And quickly retired from lab to find some vegetables.

Big Ideas Night

Aaaand we’re back for round three. This time with some new faces! Ah, time ticks on and people come and go. Fortunately for us, whiskey and science persist.

Back at the Scottish Arms, we tackled the problem of detecting simultaneous binding of two proteins to DNA; the proteins each must bind to the DNA and thus are not co-localized due to protein-protein interactions. In Barak’s words…imagine the TF a cowboy. Once on its DNA horse, it can lasso other TFs around it, but only those TFs also on horses. A wild west of a genome, indeed.

Some ideas included FRET-seq, 2-dimensional gels, and combination usage of accessibility and binding footprints. Without a clear winner, we’ll wait another day before discarding the lassos hanging from our bench top shelves. Until next time, keep thinking big, you crazy scientists.

Reflection upon a passed qualifying exam

Today in lab we were calling each other “champ”. My mom calls me Jeff. I passed my qualifying exam last Friday. Instead of providing you the blow-by-blow of my lively discussion on what sequence features determine pioneering activity, I will reflect. I hope to convey how positive an environment a lab can be.

As an MD-PhD student, I completed two years of classroom medical school prior to starting my PhD. During those first two years, I took many exams. Each exam was a real battle – from memorizing each drug used to treat heart failure to understanding how the kidney uses a litany of channels to filter our blood. By design, these two years were me against the knowledge base. Indirectly though, it was me against my classmates as we vie for a limited number of spots in competitive specialties. The result was that at times the crushing individualism led to lonely isolation.

What a difference the Cohen lab has been. A tradition of committing ourselves to each others’ crafts defines the lab, and defines the research environment at WashU. As my talk rose on the horizon, my lab mates gathered around our cozy conference table and spent hours helping me hone my ideas and sharpen my arguments to send me towards my QE. And as I stepped out of the room as my committee deliberated, there was Clarice down the hall with a wide grin on her face welcoming me back into the arms of the lab.

While the day-to-day life of medical and graduate school differ greatly, each focuses on the pursuit of knowledge. In my experience, one goes about that individually and one goes about that collaboratively. And I thank the cloning gods above that I found myself amongst the champs of Barak’s lab.

Farewell, Hemangi!

On Sunday, Barak hosted a farewell brunch for our senior graduate student, Hemangi Chaudhari. Beyond her contributions to the scientific community, Hemangi has provided wisdom and guidance to our lab for several years now. To the younger graduates, she provided patient instruction. To her classmates, she provided unbeatable cuisine and loyal companionship. And to post-docs and PIs, she provided an intellectual debate over the implications of a result or the design of an experiment.

As Hemangi moves to Boston, we wish her the warmest farewell. As she leaves behind her pipettes (to be scrounged after by incoming students) she leaves a lasting mark on both the lab and the scientific trajectories of those that were lucky enough to spend time with her in St. Louis. We all hope to cross paths again soon, as we crisscross through scientific communities all pointed towards a greater understanding of biology. While the farewells may be blue, the difficulty in parting demonstrates how strong the connections developed to be.

Farewell, Hemangi! We’ll see you again soon!

Image: Masala dosa – featured at the farewell brunch – every bite cherished (source: NY Times).

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Cohen Lab

Posts

Bissinger’s Chocolate Factory Tour

In an effort to find something sweeter than the satisfaction of sequencing DNA, the lab trekked downtown to visit St. Louis’ own Bissinger’s Chocolate Factory. Led by a couple of chocolate fanatics, we sought to uncover the secrets behind this famous chocolate. But alas, our phones were confiscated and the chocolate-factory-dungeon was threatened if we strayed from the walkway and became too pesky of visitors.

On our tour, we learned of the hand-crafted nature of Bissinger’s chocolate. A few lab members couldn’t help but be reminded of how we too take care to make sure that every library we design receives high quality and individualized attention. After the tour, we were treated to a tasting. Barak liked the chocolate-covered cherries. Siqi preferred the milk chocolate over the dark chocolate. Clarice quipped that her mint chocolate tasted like toothpaste.

All in all, we had a wonderful time. Was it sweeter than that feeling of opening up your sequencing results to find a beautiful array of A’s, C’s, T’s and G’s? Maybe not, but alas the factory was neat and the chocolate was tasty.

Qualifying Exam Successes

Congratulations to Clarice Hong (Molecular Genetics and Genomics) and Siqi Zhao (Computational and Systems Biology) on passing their Qualifying Exams!!! They have their wagons hitched to a star and we can’t wait to see where their scientific adventures travel next.

Big Ideas Night

Following the smashing success of our first big ideas night, big ideas coated our benches just as Barak’s wool sweater once did. Ideas so big that we contemplated moving into a building with even higher ceilings. But alas, we shan’t desert our loyal coffee maker, so we stay put.

The second gathering of Big Idea’s Night took place at Retreat Gastropub. Amidst some fries and whiskey, we pitched ideas for how we can utilize our Center’s newest sequencing technologies. PacBio’s ultra-long sequencing reads and the 10x single-cell method both provide new avenues for innovative research. And to not exclude our friends in imaging, we discussed a new application of FISH, called clampFISH. This technology generates a FISH signal strong enough to be detected by FACS.

The idea most discussed utilizes ultra-long reads to query chromatin interactions. In our lab, we have identified strong regional effects on gene expression. How far do these regions stretch? With our landing pad in place, we can integrate reporter genes at variable distances and ask how the length relates to the coordinated expression between the reporter gene at the LP and at distance. If we see discordance at a certain distance, it may be possible to restore the similar expression with looping-related proteins, such as CTCF or YY1. As team landing pad ventures further into the mechanisms of this strong regional effect, we will draw from these discussions and this big idea.

Hemangi’s Thesis Defense

Our intrepid landing pad explorer has successfully defended her thesis, titled “Integration of local and regional regulatory information in the human genome”!!!

Afterwards, we toasted champagne and had delicious Himalayan Yeti as we recounted Hemangi’s many wonderful accomplishments.

Big Ideas Night

The inaugural Cohen Lab Big Ideas Night! Barak loves to tell the story of the discovery of transfer RNA. Our scientific forefathers kicked around ideas over tea, scones, and maybe some beers too. Through this sort of brainstorming, the idea that there must be some molecule shuttling around amino acids was borne. Once our forefathers convinced themselves of the specifics of the idea, and how the experiment would work, actually conducting it became trivial. And thus tRNA was discovered. If such great biological discovery can be made over scones and ales, then lets indulge!

Settled into our lab’s old haunts, The Scottish Arms, we bounced around big ideas focused on master regulators. With new graduate students patrolling the benches, the lab has taken up new vocabulary as well: pioneer factors. Discussion flitted between definition, mechanism, and proof of these special transcription factors; perhaps we leave this discussion for our graduate students’ future presentations.

And so big idea #1 was not as much an idea but an open question: what would result from treating cells with two different master regulator cocktails? What type of cell would the transcriptome resemble? Would we see a random assortment of cell A and cell B, or would we see a monster, with the head of cell A and the body of cell B? With Halloween on the horizon, we’ll incubate this spooky idea until a rainy day comes along, ripe with time for a big idea experiment.

Mike White promoted to Assistant Professor

We are pleased to announce the Mike White PhD has been promoted to the rank of Assistant Professor of Genetics. This is well deserved. It is expected that Mike will continue his own research with the added distractions of worrying about grants, sitting on useless committees, and teaching classes to recalcitrant graduate students.

Listen to Barak’s Podcast with Shelina!

You can listen to the podcast here.

Brett Maricque, interviewed on “St. Louis on the Air”

Graduate student and current BALSA president, Brett Maricque, and co-founder, Maxim Schillebeeckx, discuss how the BALSA group allows graduate students to gain business experience while providing quality, low cost consulting services for the growing St. Louis biotechnology sector and generating grant money for local entrepreneurs through the BALSA Foundation. Listen to the full conversation on the “St. Louis on the Air” website.

Marc Sherman receives prestigious Spencer T. and Ann W. Olin Medical Science Fellowship

The Olin Fellowships recognize accomplishments in biomedical research by doctoral students at Washington University. While thirty-two students were nominated, only eight awards were granted. Marc’s research focused on stochasticity in gene expression and the kinds of “noise” that are often disregarded when expression is measured. While he has moved on to his clinical rotations, Marc’s work in the Cohen lab can be found under our publications header.

Mike White interviewed in St. Louis Magazine

Our own Mike White talks about what makes genetics cool in an interview for St. Louis magazine.

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Cohen Lab

Posts

Lethal Mutants win softball title

Led by team captains Brett Maricque (5th year CSB) and Kevin Forsberg (5th year MGG) the lethal mutants won the WUSM intramural softball league with a resounding win in the championship game yesterday. Well done computational biologists and molecular geneticists.

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Cohen Lab

Reflection upon a passed qualifying exam

Today in lab we were calling each other “champ”. My mom calls me Jeff. I passed my qualifying exam last Friday. Instead of providing you the blow-by-blow of my lively discussion on what sequence features determine pioneering activity, I will reflect. I hope to convey how positive an environment a lab can be.

As an MD-PhD student, I completed two years of classroom medical school prior to starting my PhD. During those first two years, I took many exams. Each exam was a real battle – from memorizing each drug used to treat heart failure to understanding how the kidney uses a litany of channels to filter our blood. By design, these two years were me against the knowledge base. Indirectly though, it was me against my classmates as we vie for a limited number of spots in competitive specialties. The result was that at times the crushing individualism led to lonely isolation.

What a difference the Cohen lab has been. A tradition of committing ourselves to each others’ crafts defines the lab, and defines the research environment at WashU. As my talk rose on the horizon, my lab mates gathered around our cozy conference table and spent hours helping me hone my ideas and sharpen my arguments to send me towards my QE. And as I stepped out of the room as my committee deliberated, there was Clarice down the hall with a wide grin on her face welcoming me back into the arms of the lab.

While the day-to-day life of medical and graduate school differ greatly, each focuses on the pursuit of knowledge. In my experience, one goes about that individually and one goes about that collaboratively. And I thank the cloning gods above that I found myself amongst the champs of Barak’s lab.

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Cohen Lab

Qualifying Exam Successes

Congratulations to Clarice Hong (Molecular Genetics and Genomics) and Siqi Zhao (Computational and Systems Biology) on passing their Qualifying Exams!!! They have their wagons hitched to a star and we can’t wait to see where their scientific adventures travel next.

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Cohen Lab

Rainbow

Look what our intrepid observer Yawei spotted outside. It seems that stay-at-home won’t stop us from making observations. Imagine that you are the first human to ever observe a rainbow, how would you explain it? Or would you rather just enjoy it?

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Cohen Lab

Papers from the lab

Ryan, Max, Clarice and Jeff all had papers published recently! You can find the links to the papers in the Publications section.

Shown above are cool illustrations that describe Clarice's and Jeff's papers. Can you spot the molecular players in these?

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Cohen Lab

Congratulations Ryan!

Congratulations to Ryan Friedman for kicking off the Cohen lab's three-defense week by successfully defending his thesis, "Iterative machine learning of a cis-regulatory grammar"! Watch a recording of the defense here.


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Cohen Lab

Congrats Ryan on your F31!

Congrats Ryan for recieving a F31 award from NHGRI ("Interpreting function of non-coding sequences with synthetic biology and machine learning").

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Cohen Lab

What is this sequence – Lab meeting – 01/14/2021

What is this sequence–
Strong, silent, or inactive?
It’s all in the bits.

Credit – Ryan Friedman

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Cohen Lab

A computationalist’s lament – Ryan’s lab meeting 8/20/20

Stay home? No problem! My work won’t be quenched.
After all, things in lab can make quite a stench.
But one fifty seven days
of work from home craze
makes me wish I did more at the bench.

Credit – Ryan Friedman

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Cohen Lab

Sailing fun

The lab spent a fun day sailing on Barak’s boat last week. The weather obliged with some great sunshine and good winds. The rejuvenated crew are now back in the lab to tackle smaller amounts of liquid.

Photo credit: James

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Cohen Lab

Sailing through graduate school

When a few Cohen Lab members found themselves listlessly floating through the doldrums of graduate school, Barak came to the rescue. Quickly navigating rivers and creeks and roadside puddles, he sailed across Illinois and arrived in lab to the shock and awe of the other landlubber labs. His new crew gave a quick “yippee” and climbed aboard.

Might there be merits to guiding the ship into international waters where the rogue scientists could set up a nautical lab? Benefits would include easy access to fresh seafood, plenty of salt water for buffering our enzymatic reactions, and the inspiration of the fresh sea breeze. That said, we may need to invent new nautical approaches to sequencing DNA, discover internet-free ways of reading new papers, and identify some Atlantis-based funding source.

For now, we’ll keep residence within our lovely coffee-laden abode and escape to Carlyle Lake when the siren song becomes too much. But when the floods arrive again, look to the Cohen Lab for the beginnings of the NNIH: the National Nautical Institutes of Health.

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Cohen Lab

Second Cohen Research Conference

The second Cohen Research Conference was held September 13-15, 2021 at Lake Geneva, WI. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board games, swimming and kayaking, a lakeside hike, a meditation session, science talks out on the deck, and more! A strong continuation of CRC tradition. Thanks to Clarice and Jeff, the chief organizers of the conference.

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Cohen Lab

Congratulations Siqi!

Congratulations to Siqi Zhao for a successful defense of his thesis, “Single-cell massively parallel reporter assays”, completing the Cohen lab June thesis defense double-header! Watch a recording of his defense here!


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Cohen Lab

Haiku – Siqi’s lab meeting 7/30

Of those sleepless nights,
how many did you consume,
stochasticity?

Credit – Siqi Zhao

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Cohen Lab

If one sings about the invisible, and to Calvino – Lab Meeting 12/03/2020

If one sings about the invisible, and to Calvino
These cities Marco Polo told the Khan,
Which are forgotten by memory now,
Only shadows exist and else are gone.
Oh Where? In Levantine but no one saw.
Ooh! A human cries for joy not for pain,
Only in Diomera with damascened wall;
And Isidora, before her all fain,
In endless desires memory is all.
It’s real? The Great Khan asks, with his back bent.
Does it matter? As light as a feather
Polo’s answer is outside the present,
Just as daydreams, do not wither.
To feel the subtlety of foreverness,
And to kiss the pain of experience.

Credit – Siqi Zhao

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Cohen Lab

Lethal Mutants win softball title

Led by team captains Brett Maricque (5th year CSB) and Kevin Forsberg (5th year MGG) the lethal mutants won the WUSM intramural softball league with a resounding win in the championship game yesterday. Well done computational biologists and molecular geneticists.

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Cohen Lab

Third Cohen Research Conference

The third annual Cohen Research Conference was held October 17-19, 2022 in Cadiz, KY. Everyone presented a talk about big questions or ideas they have. We also enjoyed communal cooking, a campfire near the water, a hike through the Land Between the Lakes National Recreation Area, moonshine tasting, puzzles and board games, guitar performances by Barak and rotation student AJ, and more! We also stopped in Metropolis, IL to see a 15-foot statue of Superman. A great time was had by all. The CRC has certainly been cemented as a lab tradition!

Photo credit: James

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Cohen Lab

We do science, too

We have a lot of fun in the Cohen Lab. We sail, and we eat donuts, and we brainstorm big ideas over tasty cocktails. But at core, we are a band of renegades, uncovering secrets of the genome. The only evidence for that claim that you’ll need is the picture below, showing Max and Maria and Clarice taking care of their cells, on a Cohen-Triple-TC-Hood-Combo-Day.

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Cohen Lab

Virtual Reunion

The virtual celebration for Dana’s paper turned into a lab Zoom reunion on April 7, 2020. It was great to see everyone who could make it and hear stories from different eras of the lab.

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Cohen Lab

Details kill – Lab meeting 05/20/2021

No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.

Credit – Yawei Wu

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Cohen Lab

Haiku was here – Lab meeting 12/17/2020

Haiku was here

From ashes of sparks,
Poets pick up left pieces,
“Hey! Poems were here”

Credit – Yawei Wu

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Cohen Lab

Gene regulation and fruit from a tree – Yawei’s lab meeting 8/7/20

Yawei started lab meeting with a cartoon depicting a model of gene regulation. See if you can figure out the analogy.

Image credit – Yawei Wu

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Cohen Lab

Publications

* These authors contributed equally to this work.

2023

Friedman RZ, Ramu A, Lichtarge S, Myers CA, Granas DM, Gause M, Corbo JC, Cohen BA, White MA Active learning of enhancer and silencer regulatory grammar in photoreceptors. bioRχiv (2023) [doi: 10.1101/2023.08.21.554146]

Shepherdson JL*, Friedman RZ*, Zheng Y, Sun C, Oh IY, Granas DM, Cohen BA, Chen S, White MA Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors. bioRχiv (2023) [doi: 10.1101/2023.05.27.542576]

Rockweiler NB, Ramu A, Nagirnaja L, Wong WH, Noordam MJ, Drubin CW, Huang N, Miller B, Todres EZ, Vigh-Conrad KA, Zito A, Small KS, Ardlie KG, Cohen BA, Conrad DF The origins and functional effects of postzygotic mutations throughout the human life span. Science (2023) [doi: 10.1126/science.abn7113]

Zhao S, Hong CKY, Myers CA, Granas DM, White MA, Corbo JC, Cohen BA A single-cell massively parallel reporter assay detects cell-type-specific gene regulation. Nature Genetics (2023) [doi: 10.1038/s41588-022-01278-7]

2022

Hong CKY, Erickson AA, Li J, Federico AJ, and Cohen BA Massively parallel characterization of insulator activity across the genome. bioRχiv (2022) [doi: 10.1101/2022.11.29.518444]

Ramu A and Cohen BA Transcription factor fluctuations underlie cell-to-cell variability in a signaling pathway response. bioRχiv (2022) [doi: 10.1101/2022.11.30.518555]

Hansen JL and Cohen BA A quantitative metric of pioneer activity reveals that HNF4A has stronger in vivo pioneer activity than FOXA1. Genome Biology (2022) [doi: 10.1186/s13059-022-02792-x]

Hong CKY*, Ramu A*, Zhao S*, Cohen BA Effect of genomic and cellular environments on gene expression noise. bioRχiv (2022) [doi: 10.1101/2022.08.31.506082]

Loell K, Wu Y, Staller MV, Cohen BA Activation domains can decouple the mean and noise of gene expression. Cell Reports (2022) [doi: 10.1016/j.celrep.2022.111118]

Staller MV, Ramirez E, Kotha SR, Holehouse AS, Pappu RV, Cohen BA Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains. Cell Systems (2022) [doi: 10.1016/j.cels.2022.01.002]

Hansen JL, Loell KJ, Cohen BA A test of the pioneer factor hypothesis using ectopic liver gene activation. eLife (2022) [doi: 10.7554/eLife.73358]

Hong CKY, Cohen BA Genomic environments scale the activities of diverse core promoters. Genome Research (2022) [doi: 10.1101/gr.276025.121]

2021

Zhao S, Pincus Z, Cohen BA Modular effects of gene promoters and chromatin environments on noise in gene expression. bioRχiv (2021) [doi: 10.1101/2021.04.29.441875]

Friedman RZ, Granas DM, Myers CA, Corbo JC, Cohen BA, White MA Information content differentiates enhancers from silencers in mouse photoreceptors. eLife (2021) [doi: 10.7554/eLife.67403]

Rockwell NC, Yang W, Warrington NM, Staller MV, Griffith M, Griffith OL, Gurnett CA, Cohen BA, Baldridge D, Rubin JB Sex- and Mutation-Specific p53 Gain-of-Function Activity in Gliomagenesis. Cancer Research Communications (2021) [doi: 10.1158/2767-9764.CRC-21-0026]

2020

King DM, Hong CKY, Shepherdson JL, Granas DM, Maricque BB, Cohen BA Synthetic and genomic regulatory elements reveal aspects of cis-regulatory grammar in mouse embryonic stem cells. eLife (2020) [doi: 10.7554/eLife.41279]

2019

Maricque BB*, Chaudhari HG*, Cohen BA A massively parallel reporter assay dissects the influence of chromatin structure on cis-regulatory activity. Nature Biotechnology (2019) [doi: 10.1038/nbt.4285]

2018

Cottrell KA, Chaudhari HG, Cohen BA, Djuranovic S PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs. Nature Communications (2018) [doi: 10.1038/s41467-017-02745-0]

Chaudhari HG, Cohen BA Local sequence features that influence AP-1 cis-regulatory activity. Genome Research (2018) [doi: 10.1101/gr.226530.117]

Staller MV, Holehouse AS, Swain-Lenz D, Das RK, Pappu RV, Cohen BA A High-Throughput Mutational Scan of an Intrinsically Disordered Acidic Transcriptional Activation Domain. Cell Systems (2018) [doi: 10.1016/j.cels.2018.01.015]

2017

Cohen BA Point of View: How should novelty be valued in science?. eLife (2017) [doi: 10.7554/eLife.28699]

Swain-Lenz D, Nikolskiy I, Cheng JY, Sudarsanam P, Nayler D, Staller MV, Cohen BA Causal Genetic Variation Underlying Metabolome Differences. Genetics (2017) [doi: 10.1534/genetics.117.203752]

Maricque BB, Dougherty JD, Cohen BA A genome-integrated massively parallel reporter assay reveals DNA sequence determinants of cis-regulatory activity in neural cells. Nucleic Acids Research (2017) [doi: 10.1093/nar/gkw942]

2016

White MA, Kwasnieski JC, Myers CA, Shen SQ, Corbo JC, Cohen BA A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors. Cell Reports (2016) [doi: 10.1016/j.celrep.2016.09.066]

Fiore C, Cohen BA Interactions between pluripotency factors specify cis-regulation in embryonic stem cells. Genome Research (2016) [doi: 10.1101/gr.200733.115]

2015

Savic D, Roberts BS, Carleton JB, Partridge EC, White MA, Cohen BA, Cooper GM, Gertz J, Myers RM Promoter-distal RNA polymerase II binding discriminates active from inactive CCAAT/enhancer-binding protein beta binding sites. Genome Research (2015) [doi: 10.1101/gr.191593.115]

White MA Understanding how cis-regulatory function is encoded in DNA sequence using massively parallel reporter assays and designed sequences. Genomics (2015) [doi: 10.1016/j.ygeno.2015.06.003]

Sherman MS, Lorenz K, Lanier MH, Cohen BA Cell-to-Cell Variability in the Propensity to Transcribe Explains Correlated Fluctuations in Gene Expression. Cell Systems (2015) [doi: 10.1016/j.cels.2015.10.011]

2014

Sudarsanam P, Cohen BA Single Nucleotide Variants in Transcription Factors Associate More Tightly with Phenotype than with Gene Expression. PLOS Genetics (2014) [doi: 10.1371/journal.pgen.1004325]

Vallania FLM, Sherman M, Goodwin Z, Mogno I, Cohen BA, Mitra RD Origin and Consequences of the Relationship between Protein Mean and Variance. PLOS One (2014) [doi: 10.1371/journal.pone.0102202]

Zeigler RD, Cohen BA Discrimination between thermodynamic models of cis-regulation using transcription factor occupancy data. Nucleic Acids Research (2014) [doi: 10.1093/nar/gkt1230]

Sherman MS, Cohen BA A Computational Framework for Analyzing Stochasticity in Gene Expression. PLOS Computational Biology (2014) [doi: 10.1371/journal.pcbi.1003596]

Kwasnieski JC*, Fiore C*, Chaudhari HG, Cohen BA High-throughput functional testing of ENCODE segmentation predictions. Genome Research (2014) [doi: 10.1101/gr.173518.114]

Lorenz K, Cohen BA Causal Variation in Yeast Sporulation Tends to Reside in a Pathway Bottleneck. PLOS Genetics (2014) [doi: 10.1371/journal.pgen.1004634]

2013

White MA, Myers CA, Corbo JC, Cohen BA Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks. PNAS (2013) [doi: 10.1073/pnas.1307449110]

Mogno I*, Kwasnieski JC*, Cohen BA Massively parallel synthetic promoter assays reveal the in vivo effects of binding site variants. Genome Research (2013) [doi: 10.1101/gr.157891.113]

2012

Sherman MS, Cohen BA Thermodynamic State Ensemble Models of cis-Regulation. PLOS Computational Biology (2012) [doi: 10.1371/journal.pcbi.1002407]

White MA, Parker DS, Barolo S, Cohen BA A model of spatially restricted transcription in opposing gradients of activators and repressors. Molecular Systems Biology (2012) [doi: 10.1038/msb.2012.48]

Lorenz K, Cohen BA Small- and Large-Effect Quantitative Trait Locus Interactions Underlie Variation in Yeast Sporulation Efficiency. Genetics (2012) [doi: 10.1534/genetics.112.143107]

Kwasnieski JC*, Mogno I*, Myers CA, Corbo JC, Cohen BA Complex effects of nucleotide variants in a mammalian cis-regulatory element. PNAS (2012) [doi: 10.1073/pnas.1210678109]

2011

Parker DS*, White MA*, Ramos AI, Cohen BA, Barolo S The cis-Regulatory Logic of Hedgehog Gradient Responses: Key Roles for Gli Binding Affinity, Competition, and Cooperativity. Science Signaling (2011) [doi: 10.1126/scisignal.2002077]

2010

Mogno I, Vallania F, Mitra RD, Cohen BA TATA is a modular component of synthetic promoters. Genome Research (2010) [doi: 10.1101/gr.106732.110]

Gertz J, Gerke JP, Cohen BA Epistasis in a quantitative trait captured by a molecular model of transcription factor interactions. Theoretical Population Biology (2010) [doi: 10.1016/j.tpb.2009.10.002]

Gerke J, Lorenz K, Ramnarine S, Cohen B Gene-Environment Interactions at Nucleotide Resolution. PLOS Genetics (2010) [doi: 10.1371/journal.pgen.1001144]

2009

Gertz J, Siggia ED, Cohen BA Analysis of combinatorial cis-regulation in synthetic and genomic promoters. Nature (2009) [doi: 10.1038/nature07521]

White MA, Riles L, Cohen BA A Systematic Screen for Transcriptional Regulators of the Yeast Cell Cycle. Genetics (2009) [doi: 10.1534/genetics.108.098145]

Gerke J, Lorenz K, Cohen B Genetic Interactions Between Transcription Factors Cause Natural Variation in Yeast. Science (2009) [doi: 10.1126/science.1166426]

Gertz J, Cohen BA Environment-specific combinatorial cis-regulation in synthetic promoters. Molecular Systems Biology (2009) [doi: 10.1038/msb2009.1]

2008

Chen CTL, Gottlieb DI, Cohen BA Ultraconserved Elements in the Olig2 Promoter. PLOS One (2008) [doi: 10.1371/journal.pone.0003946]

2007

Chen CTL, Wang JC, Cohen BA The strength of selection on ultraconserved elements in the human genome. American Journal Of Human Genetics (2007) [doi: 10.1086/513149]

Witten JT, Chen CTL, Cohen BA Complex genetic changes in strains of Saccharomyces cerevisiae derived by selection in the laboratory. Genetics (2007) [doi: 10.1534/genetics.107.077859]

Zeigler RD, Gertz J, Cohen BA A cis-regulatory logic simulator. BMC Bioinformatics (2007) [doi: 10.1186/1471-2105-8-272]

2006

Gerke JP, Chen CTL, Cohen BA Natural isolates of Saccharomyces cerevisiae display complex genetic variation in sporulation efficiency. Genetics (2006) [doi: 10.1534/genetics.106.058453]

Gertz J, Fay JC, Cohen BA Phylogeny based discovery of regulatory elements. BMC Bioinformatics (2006) [doi: 10.1186/1471-2105-7-266]

2005 and earlier

Gertz J, Riles L, Turnbaugh P, Ho SW, Cohen BA Discovery, validation, and genetic dissection of transcription factor binding sites by comparative and functional genomics. Genome Research (2005) [doi: 10.1101/gr.3859605]

Cliften P, Sudarsanam P, Desikan A, Fulton L, Fulton B, Majors J, Waterston R, Cohen BA, Johnston M Finding functional features in Saccharomyces genomes by phylogenetic footprinting. Science (2003) [doi: 10.1126/science.1084337]

Cohen BA, Pilpel Y, Mitra RD, Church GM Discrimination between paralogs using microarray analysis: Application to the Yap1p and Yap2p transcriptional networks. Molecular Biology Of The Cell (2002) [doi: 10.1091/mbc.01-10-0472]

Colas P, Cohen B, Ferrigno PK, Silver PA, Brent R Targeted modification and transportation of cellular proteins. PNAS (2000) [doi: 10.1073/pnas.97.25.13720]

Cohen BA*, Mitra RD*, Hughes JD, Church GM A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression. Nature Genetics (2000) [doi: 10.1038/79896]

Cohen BA, Colas P, Brent R An artificial cell-cycle inhibitor isolated from a combinatorial Library. PNAS (1998) [doi: 10.1073/pnas.95.24.14272]

Colas P*, Cohen B*, Jessen T, Grishina I, McCoy J, Brent R Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature (1996) [doi: 10.1038/380548a0]

Goodwin SB, Cohen BA, Fry WE Panglobal Distribution of a Single Clonal Lineage of the Irish Potato Famine Fungus. PNAS (1994) [doi: 10.1073/pnas.91.24.11591]

\ No newline at end of file diff --git a/publications/publications.csv b/publications/publications.csv new file mode 100644 index 0000000..fe552ef --- /dev/null +++ b/publications/publications.csv @@ -0,0 +1,63 @@ +title,authors,journal,publication_year,doi,featured +Active learning of enhancer and silencer regulatory grammar in photoreceptors,"Friedman RZ, Ramu A, Lichtarge S, Myers CA, Granas DM, Gause M, Corbo JC, Cohen BA, White MA",bioRχiv,2023,10.1101/2023.08.21.554146, +Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors,"Shepherdson JL*, Friedman RZ*, Zheng Y, Sun C, Oh IY, Granas DM, Cohen BA, Chen S, White MA",bioRχiv,2023,10.1101/2023.05.27.542576, +The origins and functional effects of postzygotic mutations throughout the human life span,"Rockweiler NB, Ramu A, Nagirnaja L, Wong WH, Noordam MJ, Drubin CW, Huang N, Miller B, Todres EZ, Vigh-Conrad KA, Zito A, Small KS, Ardlie KG, Cohen BA, Conrad DF",Science,2023,10.1126/science.abn7113,yes +A single-cell massively parallel reporter assay detects cell-type-specific gene regulation,"Zhao S, Hong CKY, Myers CA, Granas DM, White MA, Corbo JC, Cohen BA",Nature Genetics,2023,10.1038/s41588-022-01278-7,yes +Massively parallel characterization of insulator activity across the genome,"Hong CKY, Erickson AA, Li J, Federico AJ, and Cohen BA",bioRχiv,2022,10.1101/2022.11.29.518444, +Transcription factor fluctuations underlie cell-to-cell variability in a signaling pathway response,Ramu A and Cohen BA,bioRχiv,2022,10.1101/2022.11.30.518555, +A quantitative metric of pioneer activity reveals that HNF4A has stronger in vivo pioneer activity than FOXA1,Hansen JL and Cohen BA,Genome Biology,2022,10.1186/s13059-022-02792-x, +Effect of genomic and cellular environments on gene expression noise,"Hong CKY*, Ramu A*, Zhao S*, Cohen BA",bioRχiv,2022,10.1101/2022.08.31.506082, +Activation domains can decouple the mean and noise of gene expression,"Loell K, Wu Y, Staller MV, Cohen BA",Cell Reports,2022,10.1016/j.celrep.2022.111118, +Directed mutational scanning reveals a balance between acidic and hydrophobic residues in strong human activation domains,"Staller MV, Ramirez E, Kotha SR, Holehouse AS, Pappu RV, Cohen BA",Cell Systems,2022,10.1016/j.cels.2022.01.002, +A test of the pioneer factor hypothesis using ectopic liver gene activation,"Hansen JL, Loell KJ, Cohen BA",eLife,2022,10.7554/eLife.73358, +Genomic environments scale the activities of diverse core promoters,"Hong CKY, Cohen BA",Genome Research,2022,10.1101/gr.276025.121, +Modular effects of gene promoters and chromatin environments on noise in gene expression,"Zhao S, Pincus Z, Cohen BA",bioRχiv,2021,10.1101/2021.04.29.441875, +Information content differentiates enhancers from silencers in mouse photoreceptors,"Friedman RZ, Granas DM, Myers CA, Corbo JC, Cohen BA, White MA",eLife,2021,10.7554/eLife.67403, +Sex- and Mutation-Specific p53 Gain-of-Function Activity in Gliomagenesis,"Rockwell NC, Yang W, Warrington NM, Staller MV, Griffith M, Griffith OL, Gurnett CA, Cohen BA, Baldridge D, Rubin JB",Cancer Research Communications,2021,10.1158/2767-9764.CRC-21-0026, +Synthetic and genomic regulatory elements reveal aspects of cis-regulatory grammar in mouse embryonic stem cells,"King DM, Hong CKY, Shepherdson JL, Granas DM, Maricque BB, Cohen BA",eLife,2020,10.7554/eLife.41279, +A massively parallel reporter assay dissects the influence of chromatin structure on cis-regulatory activity,"Maricque BB*, Chaudhari HG*, Cohen BA",Nature Biotechnology,2019,10.1038/nbt.4285,yes +PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs,"Cottrell KA, Chaudhari HG, Cohen BA, Djuranovic S",Nature Communications,2018,10.1038/s41467-017-02745-0, +Local sequence features that influence AP-1 cis-regulatory activity,"Chaudhari HG, Cohen BA",Genome Research,2018,10.1101/gr.226530.117, +A High-Throughput Mutational Scan of an Intrinsically Disordered Acidic Transcriptional Activation Domain,"Staller MV, Holehouse AS, Swain-Lenz D, Das RK, Pappu RV, Cohen BA",Cell Systems,2018,10.1016/j.cels.2018.01.015, +Point of View: How should novelty be valued in science?,Cohen BA,eLife,2017,10.7554/eLife.28699, +Causal Genetic Variation Underlying Metabolome Differences,"Swain-Lenz D, Nikolskiy I, Cheng JY, Sudarsanam P, Nayler D, Staller MV, Cohen BA",Genetics,2017,10.1534/genetics.117.203752, +A genome-integrated massively parallel reporter assay reveals DNA sequence determinants of cis-regulatory activity in neural cells,"Maricque BB, Dougherty JD, Cohen BA",Nucleic Acids Research,2017,10.1093/nar/gkw942, +A Simple Grammar Defines Activating and Repressing cis-Regulatory Elements in Photoreceptors,"White MA, Kwasnieski JC, Myers CA, Shen SQ, Corbo JC, Cohen BA",Cell Reports,2016,10.1016/j.celrep.2016.09.066,yes +Interactions between pluripotency factors specify cis-regulation in embryonic stem cells,"Fiore C, Cohen BA",Genome Research,2016,10.1101/gr.200733.115, +Promoter-distal RNA polymerase II binding discriminates active from inactive CCAAT/enhancer-binding protein beta binding sites,"Savic D, Roberts BS, Carleton JB, Partridge EC, White MA, Cohen BA, Cooper GM, Gertz J, Myers RM",Genome Research,2015,10.1101/gr.191593.115, +Understanding how cis-regulatory function is encoded in DNA sequence using massively parallel reporter assays and designed sequences,White MA,Genomics,2015,10.1016/j.ygeno.2015.06.003, +Cell-to-Cell Variability in the Propensity to Transcribe Explains Correlated Fluctuations in Gene Expression,"Sherman MS, Lorenz K, Lanier MH, Cohen BA",Cell Systems,2015,10.1016/j.cels.2015.10.011, +Single Nucleotide Variants in Transcription Factors Associate More Tightly with Phenotype than with Gene Expression,"Sudarsanam P, Cohen BA",PLOS Genetics,2014,10.1371/journal.pgen.1004325,yes +Origin and Consequences of the Relationship between Protein Mean and Variance,"Vallania FLM, Sherman M, Goodwin Z, Mogno I, Cohen BA, Mitra RD",PLOS One,2014,10.1371/journal.pone.0102202, +Discrimination between thermodynamic models of cis-regulation using transcription factor occupancy data,"Zeigler RD, Cohen BA",Nucleic Acids Research,2014,10.1093/nar/gkt1230, +A Computational Framework for Analyzing Stochasticity in Gene Expression,"Sherman MS, Cohen BA",PLOS Computational Biology,2014,10.1371/journal.pcbi.1003596,yes +High-throughput functional testing of ENCODE segmentation predictions,"Kwasnieski JC*, Fiore C*, Chaudhari HG, Cohen BA",Genome Research,2014,10.1101/gr.173518.114, +Causal Variation in Yeast Sporulation Tends to Reside in a Pathway Bottleneck,"Lorenz K, Cohen BA",PLOS Genetics,2014,10.1371/journal.pgen.1004634, +Massively parallel in vivo enhancer assay reveals that highly local features determine the cis-regulatory function of ChIP-seq peaks,"White MA, Myers CA, Corbo JC, Cohen BA",PNAS,2013,10.1073/pnas.1307449110,yes +Massively parallel synthetic promoter assays reveal the in vivo effects of binding site variants,"Mogno I*, Kwasnieski JC*, Cohen BA",Genome Research,2013,10.1101/gr.157891.113, +Thermodynamic State Ensemble Models of cis-Regulation,"Sherman MS, Cohen BA",PLOS Computational Biology,2012,10.1371/journal.pcbi.1002407, +A model of spatially restricted transcription in opposing gradients of activators and repressors,"White MA, Parker DS, Barolo S, Cohen BA",Molecular Systems Biology,2012,10.1038/msb.2012.48, +Small- and Large-Effect Quantitative Trait Locus Interactions Underlie Variation in Yeast Sporulation Efficiency,"Lorenz K, Cohen BA",Genetics,2012,10.1534/genetics.112.143107, +Complex effects of nucleotide variants in a mammalian cis-regulatory element,"Kwasnieski JC*, Mogno I*, Myers CA, Corbo JC, Cohen BA",PNAS,2012,10.1073/pnas.1210678109,yes +"The cis-Regulatory Logic of Hedgehog Gradient Responses: Key Roles for Gli Binding Affinity, Competition, and Cooperativity","Parker DS*, White MA*, Ramos AI, Cohen BA, Barolo S",Science Signaling,2011,10.1126/scisignal.2002077,yes +TATA is a modular component of synthetic promoters,"Mogno I, Vallania F, Mitra RD, Cohen BA",Genome Research,2010,10.1101/gr.106732.110, +Epistasis in a quantitative trait captured by a molecular model of transcription factor interactions,"Gertz J, Gerke JP, Cohen BA",Theoretical Population Biology,2010,10.1016/j.tpb.2009.10.002, +Gene-Environment Interactions at Nucleotide Resolution,"Gerke J, Lorenz K, Ramnarine S, Cohen B",PLOS Genetics,2010,10.1371/journal.pgen.1001144, +Analysis of combinatorial cis-regulation in synthetic and genomic promoters,"Gertz J, Siggia ED, Cohen BA",Nature,2009,10.1038/nature07521,yes +A Systematic Screen for Transcriptional Regulators of the Yeast Cell Cycle,"White MA, Riles L, Cohen BA",Genetics,2009,10.1534/genetics.108.098145, +Genetic Interactions Between Transcription Factors Cause Natural Variation in Yeast,"Gerke J, Lorenz K, Cohen B",Science,2009,10.1126/science.1166426,yes +Environment-specific combinatorial cis-regulation in synthetic promoters,"Gertz J, Cohen BA",Molecular Systems Biology,2009,10.1038/msb2009.1, +Ultraconserved Elements in the Olig2 Promoter,"Chen CTL, Gottlieb DI, Cohen BA",PLOS One,2008,10.1371/journal.pone.0003946, +The strength of selection on ultraconserved elements in the human genome,"Chen CTL, Wang JC, Cohen BA",American Journal Of Human Genetics,2007,10.1086/513149,yes +Complex genetic changes in strains of Saccharomyces cerevisiae derived by selection in the laboratory,"Witten JT, Chen CTL, Cohen BA",Genetics,2007,10.1534/genetics.107.077859, +A cis-regulatory logic simulator,"Zeigler RD, Gertz J, Cohen BA",BMC Bioinformatics,2007,10.1186/1471-2105-8-272, +Natural isolates of Saccharomyces cerevisiae display complex genetic variation in sporulation efficiency,"Gerke JP, Chen CTL, Cohen BA",Genetics,2006,10.1534/genetics.106.058453, +Phylogeny based discovery of regulatory elements,"Gertz J, Fay JC, Cohen BA",BMC Bioinformatics,2006,10.1186/1471-2105-7-266, +"Discovery, validation, and genetic dissection of transcription factor binding sites by comparative and functional genomics","Gertz J, Riles L, Turnbaugh P, Ho SW, Cohen BA",Genome Research,2005,10.1101/gr.3859605, +Finding functional features in Saccharomyces genomes by phylogenetic footprinting,"Cliften P, Sudarsanam P, Desikan A, Fulton L, Fulton B, Majors J, Waterston R, Cohen BA, Johnston M",Science,2003,10.1126/science.1084337,yes +Discrimination between paralogs using microarray analysis: Application to the Yap1p and Yap2p transcriptional networks,"Cohen BA, Pilpel Y, Mitra RD, Church GM",Molecular Biology Of The Cell,2002,10.1091/mbc.01-10-0472, +Targeted modification and transportation of cellular proteins,"Colas P, Cohen B, Ferrigno PK, Silver PA, Brent R",PNAS,2000,10.1073/pnas.97.25.13720, +A computational analysis of whole-genome expression data reveals chromosomal domains of gene expression,"Cohen BA*, Mitra RD*, Hughes JD, Church GM",Nature Genetics,2000,10.1038/79896, +An artificial cell-cycle inhibitor isolated from a combinatorial Library,"Cohen BA, Colas P, Brent R",PNAS,1998,10.1073/pnas.95.24.14272, +Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2,"Colas P*, Cohen B*, Jessen T, Grishina I, McCoy J, Brent R",Nature,1996,10.1038/380548a0, +Panglobal Distribution of a Single Clonal Lineage of the Irish Potato Famine Fungus,"Goodwin SB, Cohen BA, Fry WE",PNAS,1994,10.1073/pnas.91.24.11591, diff --git a/research/cell-type-specific-expression/index.html b/research/cell-type-specific-expression/index.html new file mode 100644 index 0000000..28b66d5 --- /dev/null +++ b/research/cell-type-specific-expression/index.html @@ -0,0 +1 @@ +Cohen Lab/Research/Determinants of cell type specific gene expression

Cohen Lab

Determinants of cell type specific gene expression

[all research areas]

We are interested in identifying the specific DNA features that “program” the genome to express certain genes in particular cell types. We are working in a variety of cell types including embryonic stem cells, lymphoblastoid cell lines, and neuronal cell lines in the brains of live mice.

\ No newline at end of file diff --git a/research/index.html b/research/index.html new file mode 100644 index 0000000..9a089cd --- /dev/null +++ b/research/index.html @@ -0,0 +1 @@ +Cohen Lab/Research

Cohen Lab

Research

Gene Regulatory Genomics

What is the contribution of non-protein coding genetic variation to human disease? Genetic mapping studies tell us that non-coding DNA harbors the majority of variation that contributes to disease, but, we have virtually no ability to identify the specific disease-causing nucleotides in non-coding DNA. In protein-coding DNA the genetic code helps us interpret the likely effects of sequence changes, but we have no corresponding “non-coding code” for the 98% of the genome that does not code for protein. Does a non-coding code exist that might help us identify and understand disease causing variants?

Possibly.

A common hypothesis is that the majority of non-coding disease variants lie in enhancers, which are short DNA sequences that influence the transcription of nearby genes. Enhancers are in turn comprised of binding sites for transcription factors and other sequences that influence the shape and accessibility of DNA. While it is unlikely that a simple DNA code exists to explain the activity of enhancers, the arrangements of binding sites and sequence features in enhancers often conform to certain physical constraints. Based on these observations we hypothesize that enhancers are subject to a “cis-regulatory grammar”, which governs the functional consequences of arrangements of transcription factor binding sites in the genome. The goal of our lab is to identify and formalize the “rules” that might comprise a non-coding DNA grammar. Such rules would be powerful new agents for interpreting disease causing genetic variation by allowing us to identify new enhancers in non-coding DNA and to predict the effects of sequence variation on existing enhancers

How can we identify the rules that might comprise a cis-regulatory grammar? We base our approach on a simple historical fact. Namely, that the genetic code was cracked by synthetic biologists. Starting with Marshall Nirenberg and Heinrich Matthaei, in 1961 investigators began constructing artificial RNAs and recording the resulting polypeptides that were produced. From these data the genetic code was deduced. In a modern twist of this idea we leverage advances in highly parallel DNA synthesis technologies to synthesize and measure the activity of tens of thousands of designer artificial enhancers. These artificial enhancers are comprised of combinations of transcription factor binding sites, nucleosome positioning signals, and DNA shape determining sequences. Using techniques from machine learning and statistical thermodynamics we deduce the rules that govern the activities of enhancers.

With these approaches our ultimate goal is to produce formal, quantitative models that accurately predict the effects of DNA sequence changes on gene regulation. Such models will be invaluable tools for identifying the particular causal variants in a large number of disease-associated genomic regions.

Our efforts are focused on several projects:

  1. Massively parallel assays of cis-regulatory elements

    We are developing a suite of experimental technologies to design, construct, and assay tens of thousands of reporter genes in a single experiment.

  2. Thermodynamic models of cis-regulation

    We are exploring the use of concepts from statistical physics as a formal way to model how interactions between transcription factors and DNA lead to specific patterns of gene expression.

  3. Determinants of cell type specific gene expression

    We are interested in identifying the specific DNA features that “program” the genome to express certain genes in particular cell types. We are working in a variety of cell types including embryonic stem cells, lymphoblastoid cell lines, and neuronal cell lines in the brains of live mice.

  4. Determinants of specificity in mammalian genomes

    A key question is how the cell distinguishes groups of transcription factor binding sites that make up real enhancers from spurious collections of binding sites. Here we leverage our ability to design thousands of artificial enhancers to unravel the sequence features adjacent to functional versus non-functional instances of transcription factor binding sites.

  5. Stochastic models of cis-regulation

    We are investigating how stochastic fluctuations in gene expression can inform on the mechanism enhancers use to activate gene expression.

  6. The relationship of genetic variation in cis-regulation to natural phenotypic variation between individuals

    Ultimately we care about the effect of variation in gene regulation on the phenotypes of organisms. To this end we are mapping and identifying cis-regulatory variation that affects cellular phenotypes in yeast, and we are attempting to identify the causal variants in regions identified in human genetic mapping studies.

\ No newline at end of file diff --git a/research/mpras/index.html b/research/mpras/index.html new file mode 100644 index 0000000..3f463f3 --- /dev/null +++ b/research/mpras/index.html @@ -0,0 +1 @@ +Cohen Lab/Research/Massively parallel assays of *cis*-regulatory elements

Cohen Lab

Massively parallel assays of cis-regulatory elements

[all research areas]

We are developing a suite of experimental technologies to design, construct, and assay tens of thousands of reporter genes in a single experiment.

\ No newline at end of file diff --git a/research/natural-variation/index.html b/research/natural-variation/index.html new file mode 100644 index 0000000..49def7a --- /dev/null +++ b/research/natural-variation/index.html @@ -0,0 +1 @@ +Cohen Lab/Research/The relationship of genetic variation in *cis*-regulation to natural phenotypic variation between individuals

Cohen Lab

The relationship of genetic variation in cis-regulation to natural phenotypic variation between individuals

[all research areas]

Ultimately we care about the effect of variation in gene regulation on the phenotypes of organisms. To this end we are mapping and identifying cis-regulatory variation that affects cellular phenotypes in yeast, and we are attempting to identify the causal variants in regions identified in human genetic mapping studies.

\ No newline at end of file diff --git a/research/specificity/index.html b/research/specificity/index.html new file mode 100644 index 0000000..4649872 --- /dev/null +++ b/research/specificity/index.html @@ -0,0 +1 @@ +Cohen Lab/Research/Determinants of specificity in mammalian genomes

Cohen Lab

Determinants of specificity in mammalian genomes

[all research areas]

A key question is how the cell distinguishes groups of transcription factor binding sites that make up real enhancers from spurious collections of binding sites. Here we leverage our ability to design thousands of artificial enhancers to unravel the sequence features adjacent to functional versus non-functional instances of transcription factor binding sites.

\ No newline at end of file diff --git a/research/stochastic-models/index.html b/research/stochastic-models/index.html new file mode 100644 index 0000000..2c48981 --- /dev/null +++ b/research/stochastic-models/index.html @@ -0,0 +1 @@ +Cohen Lab/Research/Stochastic models of *cis*-regulation

Cohen Lab

Stochastic models of cis-regulation

[all research areas]

We are investigating how stochastic fluctuations in gene expression can inform on the mechanism enhancers use to activate gene expression.

\ No newline at end of file diff --git a/research/thermodynamic-models/index.html b/research/thermodynamic-models/index.html new file mode 100644 index 0000000..64d7511 --- /dev/null +++ b/research/thermodynamic-models/index.html @@ -0,0 +1 @@ +Cohen Lab/Research/Thermodynamic models of *cis*-regulation

Cohen Lab

Thermodynamic models of cis-regulation

[all research areas]

We are exploring the use of concepts from statistical physics as a formal way to model how interactions between transcription factors and DNA lead to specific patterns of gene expression.

\ No newline at end of file diff --git a/resources/index.html b/resources/index.html new file mode 100644 index 0000000..2b5fa27 --- /dev/null +++ b/resources/index.html @@ -0,0 +1 @@ +Cohen Lab/Resources

Cohen Lab

Resources

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https://bclab.wustl.edu/authors/Ryan/ + + + https://bclab.wustl.edu/authors/Ryan/page/1/ + + + https://bclab.wustl.edu/contact/ + + + https://bclab.wustl.edu/journal-club/ + + + https://bclab.wustl.edu/people/ + + + https://bclab.wustl.edu/posts/ + + + https://bclab.wustl.edu/posts/asbmb-meeting/ + 2022-07-25 + + + https://bclab.wustl.edu/posts/avi-defense/ + 2023-05-04 + + + https://bclab.wustl.edu/posts/avi-haiku/ + 2021-03-11 + + + https://bclab.wustl.edu/posts/back-to-back-proposals/ + 2018-10-08 + + + https://bclab.wustl.edu/posts/barak-ai-prank/ + 2023-01-12 + + + https://bclab.wustl.edu/posts/barak-limerick-2/ + 2021-01-21 + + + https://bclab.wustl.edu/posts/barak-limerick/ + 2020-08-27 + + + https://bclab.wustl.edu/posts/barak-shelina-podcast/ + 2015-05-06 + + + https://bclab.wustl.edu/posts/big-ideas-night-2017-10-15/ + 2017-10-15 + + + https://bclab.wustl.edu/posts/big-ideas-night-2018-01-25/ + 2018-01-25 + + + https://bclab.wustl.edu/posts/big-ideas-night-2018-06-01/ + 2018-06-01 + + + https://bclab.wustl.edu/posts/bissingers/ + 2018-02-24 + + + https://bclab.wustl.edu/posts/brett-balsa-interview/ + 2015-02-02 + + + https://bclab.wustl.edu/posts/clarice-defense/ + 2022-12-02 + + + https://bclab.wustl.edu/posts/clarice-limerick/ + 2020-10-15 + + + https://bclab.wustl.edu/posts/clarice-poem/ + 2021-04-01 + + + https://bclab.wustl.edu/posts/donut-day/ + 2018-10-02 + + + https://bclab.wustl.edu/posts/dustin-limerick/ + 2020-11-19 + + + https://bclab.wustl.edu/posts/farewell-hemangi/ + 2018-04-19 + + + https://bclab.wustl.edu/posts/first-cohen-research-conference/ + 2020-03-01 + + + https://bclab.wustl.edu/posts/fourth-cohen-research-conference/ + 2023-10-23 + + + https://bclab.wustl.edu/posts/goodbye-jeff-siqi/ + 2022-06-18 + + + https://bclab.wustl.edu/posts/goodbye-max/ + 2021-01-28 + + + https://bclab.wustl.edu/posts/goodbye-ryan-avi-kai/ + 2023-05-29 + + + https://bclab.wustl.edu/posts/hemangi-defense/ + 2017-12-20 + + + https://bclab.wustl.edu/posts/james-f/ + 2022-02-10 + + + https://bclab.wustl.edu/posts/jeff-defense/ + 2022-06-01 + + + https://bclab.wustl.edu/posts/jeff-limerick/ + 2020-09-24 + + + https://bclab.wustl.edu/posts/jeff-poem/ + 2021-05-27 + + + https://bclab.wustl.edu/posts/jeff-spot/ + 2021-02-11 + + + https://bclab.wustl.edu/posts/kai-ad-paper/ + 2022-07-28 + + + https://bclab.wustl.edu/posts/kai-defense/ + 2023-05-09 + + + https://bclab.wustl.edu/posts/kai-haiku/ + 2021-02-04 + + + https://bclab.wustl.edu/posts/kai-limerick/ + 2021-05-13 + + + https://bclab.wustl.edu/posts/marc-olin-fellowship/ + 2015-02-02 + + + https://bclab.wustl.edu/posts/max-k/ + 2019-02-06 + + + https://bclab.wustl.edu/posts/mike-assistant-professor/ + 2015-08-12 + + + https://bclab.wustl.edu/posts/mike-haiku/ + 2021-03-04 + + + https://bclab.wustl.edu/posts/mike-interview/ + 2014-08-26 + + + https://bclab.wustl.edu/posts/nicole-limerick/ + 2020-08-13 + + + https://bclab.wustl.edu/posts/page/1/ + + + https://bclab.wustl.edu/posts/page/2/ + + + https://bclab.wustl.edu/posts/page/3/ + + + https://bclab.wustl.edu/posts/page/4/ + + + https://bclab.wustl.edu/posts/page/5/ + + + https://bclab.wustl.edu/posts/page/6/ + + + https://bclab.wustl.edu/posts/page/7/ + + + https://bclab.wustl.edu/posts/qe-reflection/ + 2018-06-01 + + + https://bclab.wustl.edu/posts/qe-success/ + 2018-01-26 + + + https://bclab.wustl.edu/posts/rainbow/ + 2020-08-25 + + + https://bclab.wustl.edu/posts/recent-publications/ + 2022-02-21 + + + https://bclab.wustl.edu/posts/ryan-defense/ + 2023-05-02 + + + https://bclab.wustl.edu/posts/ryan-f/ + 2020-07-08 + + + https://bclab.wustl.edu/posts/ryan-haiku/ + 2021-01-14 + + + https://bclab.wustl.edu/posts/ryan-limerick/ + 2020-08-20 + + + https://bclab.wustl.edu/posts/sailing-fun/ + 2019-09-24 + + + https://bclab.wustl.edu/posts/sailing-through-grad-school/ + 2018-10-08 + + + https://bclab.wustl.edu/posts/second-cohen-research-conference/ + 2021-09-16 + + + https://bclab.wustl.edu/posts/siqi-defense/ + 2022-06-15 + + + https://bclab.wustl.edu/posts/siqi-haiku/ + 2020-07-30 + + + https://bclab.wustl.edu/posts/siqi-poem/ + 2020-12-03 + + + https://bclab.wustl.edu/posts/softball/ + 2014-08-07 + + + https://bclab.wustl.edu/posts/third-cohen-research-conference/ + 2022-10-26 + + + https://bclab.wustl.edu/posts/triple-tc-hood/ + 2019-01-07 + + + https://bclab.wustl.edu/posts/virtual-reunion/ + 2020-04-07 + + + https://bclab.wustl.edu/posts/yawei-haiku-2/ + 2021-05-20 + + + https://bclab.wustl.edu/posts/yawei-haiku/ + 2020-12-17 + + + https://bclab.wustl.edu/posts/yawei-tree/ + 2020-08-07 + + + https://bclab.wustl.edu/publications/ + + + https://bclab.wustl.edu/research/ + + + https://bclab.wustl.edu/research/cell-type-specific-expression/ + + + https://bclab.wustl.edu/research/mpras/ + + + https://bclab.wustl.edu/research/natural-variation/ + + + https://bclab.wustl.edu/research/specificity/ + + + https://bclab.wustl.edu/research/stochastic-models/ + + + https://bclab.wustl.edu/research/thermodynamic-models/ + + + https://bclab.wustl.edu/resources/ + + + https://bclab.wustl.edu/tags/ + + + https://bclab.wustl.edu/tags/awards/ + + + https://bclab.wustl.edu/tags/awards/page/1/ + + + https://bclab.wustl.edu/tags/big-ideas-night/ + + + https://bclab.wustl.edu/tags/big-ideas-night/page/1/ + + + https://bclab.wustl.edu/tags/fun/ + + + https://bclab.wustl.edu/tags/fun/page/1/ + + + https://bclab.wustl.edu/tags/fun/page/2/ + + + https://bclab.wustl.edu/tags/lab-meeting-poetry/ + + + https://bclab.wustl.edu/tags/lab-meeting-poetry/page/1/ + + + https://bclab.wustl.edu/tags/lab-meeting-poetry/page/2/ + + + https://bclab.wustl.edu/tags/milestones/ + + + https://bclab.wustl.edu/tags/milestones/page/1/ + + + https://bclab.wustl.edu/tags/milestones/page/2/ + + + https://bclab.wustl.edu/tags/news/ + + + https://bclab.wustl.edu/tags/news/page/1/ + + + https://bclab.wustl.edu/tags/science/ + + + 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Cohen Lab attends ASBMB meeting

Mike, Clarice, Ryan, Kai, and Yawei recently traveled to the Stowers Institute in Kansas City to attend the ASBMB conference "Evolution and Core Processes in Gene Expresson". Clarice gave a talk and everyone else presented a poster. Congratulations to Yawei, who was awarded a Best Poster Award for a graduate student!

We had a great time learning about the latest research in cis-regulatory grammar, enhancer evolution, and predictive models of gene regulation. We also enjoyed eating some delicious Kansas City BBQ and connecting with our peers and colleagues in the field.

James F30 Success

Congrats James for recieving a F30 award from NEI for the project "Multiplex functional assay of variant effect in the retinal transcription factor CRX".

Congrats Ryan on your F31!

Congrats Ryan for recieving a F31 award from NHGRI ("Interpreting function of non-coding sequences with synthetic biology and machine learning").

Max K99 Success

Great work Max for recieving a K99 award from NIGMS for his project "High-Throughput Functional Interrogation Of Mammalian Activation Domains".

Marc Sherman receives prestigious Spencer T. and Ann W. Olin Medical Science Fellowship

The Olin Fellowships recognize accomplishments in biomedical research by doctoral students at Washington University. While thirty-two students were nominated, only eight awards were granted. Marc’s research focused on stochasticity in gene expression and the kinds of “noise” that are often disregarded when expression is measured. While he has moved on to his clinical rotations, Marc’s work in the Cohen lab can be found under our publications header.

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Posts tagged #big-ideas-night

Big Ideas Night

Aaaand we’re back for round three. This time with some new faces! Ah, time ticks on and people come and go. Fortunately for us, whiskey and science persist.

Back at the Scottish Arms, we tackled the problem of detecting simultaneous binding of two proteins to DNA; the proteins each must bind to the DNA and thus are not co-localized due to protein-protein interactions. In Barak’s words…imagine the TF a cowboy. Once on its DNA horse, it can lasso other TFs around it, but only those TFs also on horses. A wild west of a genome, indeed.

Some ideas included FRET-seq, 2-dimensional gels, and combination usage of accessibility and binding footprints. Without a clear winner, we’ll wait another day before discarding the lassos hanging from our bench top shelves. Until next time, keep thinking big, you crazy scientists.

Big Ideas Night

Following the smashing success of our first big ideas night, big ideas coated our benches just as Barak’s wool sweater once did. Ideas so big that we contemplated moving into a building with even higher ceilings. But alas, we shan’t desert our loyal coffee maker, so we stay put.

The second gathering of Big Idea’s Night took place at Retreat Gastropub. Amidst some fries and whiskey, we pitched ideas for how we can utilize our Center’s newest sequencing technologies. PacBio’s ultra-long sequencing reads and the 10x single-cell method both provide new avenues for innovative research. And to not exclude our friends in imaging, we discussed a new application of FISH, called clampFISH. This technology generates a FISH signal strong enough to be detected by FACS.

The idea most discussed utilizes ultra-long reads to query chromatin interactions. In our lab, we have identified strong regional effects on gene expression. How far do these regions stretch? With our landing pad in place, we can integrate reporter genes at variable distances and ask how the length relates to the coordinated expression between the reporter gene at the LP and at distance. If we see discordance at a certain distance, it may be possible to restore the similar expression with looping-related proteins, such as CTCF or YY1. As team landing pad ventures further into the mechanisms of this strong regional effect, we will draw from these discussions and this big idea.

Big Ideas Night

The inaugural Cohen Lab Big Ideas Night! Barak loves to tell the story of the discovery of transfer RNA. Our scientific forefathers kicked around ideas over tea, scones, and maybe some beers too. Through this sort of brainstorming, the idea that there must be some molecule shuttling around amino acids was borne. Once our forefathers convinced themselves of the specifics of the idea, and how the experiment would work, actually conducting it became trivial. And thus tRNA was discovered. If such great biological discovery can be made over scones and ales, then lets indulge!

Settled into our lab’s old haunts, The Scottish Arms, we bounced around big ideas focused on master regulators. With new graduate students patrolling the benches, the lab has taken up new vocabulary as well: pioneer factors. Discussion flitted between definition, mechanism, and proof of these special transcription factors; perhaps we leave this discussion for our graduate students’ future presentations.

And so big idea #1 was not as much an idea but an open question: what would result from treating cells with two different master regulator cocktails? What type of cell would the transcriptome resemble? Would we see a random assortment of cell A and cell B, or would we see a monster, with the head of cell A and the body of cell B? With Halloween on the horizon, we’ll incubate this spooky idea until a rainy day comes along, ripe with time for a big idea experiment.

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Fourth Cohen Research Conference

The fourth annual Cohen Research Conference was held October 23-25, 2023 in Michigan City, IN. Lab members presented talks on big ideas or out-there experiments. Continuing the tradition from prior CRCs, we also enjoyed communal cooking, a campfire near the lake, and a dunes hike in Indiana Dunes National Park which passed through Cowles Bog, a site of seminal research on ecological succession!

Goodbye Ryan, Avi, and Kai!

The lab met at Barak's house to congratulate Ryan, Avi and Kai on their successful thesis defenses and wish them well in their next endeavors! Ryan will be starting a postdoc in Cole Trapnell's lab at UW, Avi will be joining the team at Verily Life Sciences, and Kai will be starting a postdoc in Justin Kinney's lab at CSHL.

AI Art Gallery in Barak's Office

When the PI is away, the grad students play!

Every year when Barak goes out of town for a long time, we prank his office as a welcome back surprise. Barak has recently taken a strong interest in Paul Cezanne, so this year we turned his office into an art gallery. We used the AI DALL-E 2 to generate fake art and hung it next to real art. We used another AI called ChatGPT to generate fake museum labels to accompany the fake art.

In addition, James used 24 photos of Barak from over the years and the "Dreambooth" technique to teach another AI, Stable Diffusion, what Barak looks like. Then, James asked Stable Diffusion to generate portraits of Barak in the style of several different artists. The collection of portraits is truly stunning -- there's even a museum label from ChatGPT emphasizing the mystery of the portraits' recurring subject!

Here are some pictures of the decor. Can you tell which pieces are real works of art?

Below is what ChatGPT had to say about the portrait collection:

"The Many Faces of _______: A Portrait Collection"

This collection features a series of portrait paintings, all depicting the same individual. The artwork on display was created by a diverse group of artists, each bringing their own unique style and perspective to the portrayed subject.

Who was this person, and why were they painted by so many different artists? These paintings offer a glimpse into the life and personality of the subject, but leave much to the imagination.

From the traditional techniques of the Old Masters, to the bold brushstrokes and vibrant colors of modern art, this collection showcases the versatility and enduring appeal of portraiture. The subjects depicted range from formal poses in elegant attire, to more relaxed and casual depictions.

Despite the varied styles and approaches, each of these paintings captures the essence of the subject and conveys a sense of their personality. This collection serves as a testament to the enduring power of portraiture as a means of preserving the human spirit on canvas, and leaves us wondering about the mystery of the person depicted.

Third Cohen Research Conference

The third annual Cohen Research Conference was held October 17-19, 2022 in Cadiz, KY. Everyone presented a talk about big questions or ideas they have. We also enjoyed communal cooking, a campfire near the water, a hike through the Land Between the Lakes National Recreation Area, moonshine tasting, puzzles and board games, guitar performances by Barak and rotation student AJ, and more! We also stopped in Metropolis, IL to see a 15-foot statue of Superman. A great time was had by all. The CRC has certainly been cemented as a lab tradition!

Photo credit: James

Summer Cookout — Goodbye, Jeff and Siqi!

The lab joined family and friends to celebrate Jeff and Siqi's successful defenses with a backyard cookout! Barak presented a book to each of the graduates, and everyone was treated to a magic show … um, I mean scientific demonstration of the power of ESP.

Papers from the lab

Ryan, Max, Clarice and Jeff all had papers published recently! You can find the links to the papers in the Publications section.

Shown above are cool illustrations that describe Clarice's and Jeff's papers. Can you spot the molecular players in these?

Second Cohen Research Conference

The second Cohen Research Conference was held September 13-15, 2021 at Lake Geneva, WI. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board games, swimming and kayaking, a lakeside hike, a meditation session, science talks out on the deck, and more! A strong continuation of CRC tradition. Thanks to Clarice and Jeff, the chief organizers of the conference.

Rainbow

Look what our intrepid observer Yawei spotted outside. It seems that stay-at-home won’t stop us from making observations. Imagine that you are the first human to ever observe a rainbow, how would you explain it? Or would you rather just enjoy it?

Virtual Reunion

The virtual celebration for Dana’s paper turned into a lab Zoom reunion on April 7, 2020. It was great to see everyone who could make it and hear stories from different eras of the lab.

First Cohen Research Conference

The first-ever Cohen Research Conference was held Feb 25-27, 2020 at Stonehaven Castle, Eureka Springs, AR. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board-games, day-time and night-time hikes, a meditation session, sciencing around a campfire, spotting constellations on a clear black sky, balancing the entire lab on a log, and impromptu midnight performances with the guitar by Barak. It was a truly special experience. Thanks to Clarice and Jeff, the chief organizers of the conference.

Photo credit: James

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Sailing fun

The lab spent a fun day sailing on Barak’s boat last week. The weather obliged with some great sunshine and good winds. The rejuvenated crew are now back in the lab to tackle smaller amounts of liquid.

Photo credit: James

Sailing through graduate school

When a few Cohen Lab members found themselves listlessly floating through the doldrums of graduate school, Barak came to the rescue. Quickly navigating rivers and creeks and roadside puddles, he sailed across Illinois and arrived in lab to the shock and awe of the other landlubber labs. His new crew gave a quick “yippee” and climbed aboard.

Might there be merits to guiding the ship into international waters where the rogue scientists could set up a nautical lab? Benefits would include easy access to fresh seafood, plenty of salt water for buffering our enzymatic reactions, and the inspiration of the fresh sea breeze. That said, we may need to invent new nautical approaches to sequencing DNA, discover internet-free ways of reading new papers, and identify some Atlantis-based funding source.

For now, we’ll keep residence within our lovely coffee-laden abode and escape to Carlyle Lake when the siren song becomes too much. But when the floods arrive again, look to the Cohen Lab for the beginnings of the NNIH: the National Nautical Institutes of Health.

Donut Day in the Cohen Lab

Mary Poppins sang that a spoonful of sugar helps the medicine go down. This morning, we sang that a dozen John’s donuts helps the Washington University in St. Louis Institutional Biological & Chemical Safety Committee Protocol go down, and an additional spoonful of sugar helps that lengthy name go down.

Around the rooster’s crow, Barak, Max, Clarice, and Jeff gathered round a table piled high with past protocols, laptops, safety certificates, and a hearty collective knowledge ranging from the origins of reporter genes to the dangers of graphite in space. And then there were the donuts. Our lab has a storied tradition of sweetening unpleasant days with samplings of St. Louis’ fabulous donut scene. For RNA extractions, we grab a dozen from World’s Fair. For library preparation, we grab a dozen from Vincent Van Doughnut. For Clarice’s seven-hour-long marathon of a practice talk, we grab a dozen from Strange. And for the latest effort in maintaining a safe and accountable lab, we grab a dozen from John’s.

Perched next to our venerable coffee source, the four toiled as the sun progressed across the sky. Time’s passing was marked only by the regular flow of fellow scientists, coming to refill their receptacles with the dark brown life fuel that surely represents far too high of a proportion within our electrolyte-deficient bloodstream. Some offered sympathies, while others jealously eyed the donuts. The latter group hoped to only experience the sweet without the accompanying sour.

As the crescent moon rose on the horizon, the protocol neared complete. The four, splitting the final donut into quarters, each raised a piece in cheers to renewed safety and accountability. And quickly retired from lab to find some vegetables.

Bissinger’s Chocolate Factory Tour

In an effort to find something sweeter than the satisfaction of sequencing DNA, the lab trekked downtown to visit St. Louis’ own Bissinger’s Chocolate Factory. Led by a couple of chocolate fanatics, we sought to uncover the secrets behind this famous chocolate. But alas, our phones were confiscated and the chocolate-factory-dungeon was threatened if we strayed from the walkway and became too pesky of visitors.

On our tour, we learned of the hand-crafted nature of Bissinger’s chocolate. A few lab members couldn’t help but be reminded of how we too take care to make sure that every library we design receives high quality and individualized attention. After the tour, we were treated to a tasting. Barak liked the chocolate-covered cherries. Siqi preferred the milk chocolate over the dark chocolate. Clarice quipped that her mint chocolate tasted like toothpaste.

All in all, we had a wonderful time. Was it sweeter than that feeling of opening up your sequencing results to find a beautiful array of A’s, C’s, T’s and G’s? Maybe not, but alas the factory was neat and the chocolate was tasty.

Lethal Mutants win softball title

Led by team captains Brett Maricque (5th year CSB) and Kevin Forsberg (5th year MGG) the lethal mutants won the WUSM intramural softball league with a resounding win in the championship game yesterday. Well done computational biologists and molecular geneticists.

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Posts tagged #lab-meeting-poetry

Jeff, Bagel, Beer – Lab Meeting 05/27/2021

Jeff
Genome
Genetics
Phonetics
Photon
Roton
Rotor
Motor
Money
Honey
Bunny
Bagel
Kegel
Candy
Dandy
Dandruff
Beard scruff
Beer
Fear
Deer
Donuts

Credit – Jeff Hansen

Details kill – Lab meeting 05/20/2021

No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.

Credit – Yawei Wu

There once were some yeast – Lab Meeting 05/13/2021

There once were some yeast from afar
That simply would not PCR
Boiling, freezing were no use
So they got ground up and juiced
And now show their genetic scars

Credit – Kai Loell

Insulator – Lab meeting 04/01/2021

It hides in black and dark genomic space
Though with enhancers it must intervene
And once called junk by many in old days
It found fame in the chicken globin gene.
The saw cHS4 had magic game
The researchers who found it thus cried out
O insulator thou art not the same
Now with you loops will never be in doubt.
But then one day a graduate student thought
I wonder how you’ll fare in landing pads
Alas her efforts always came to naught
Much time was wasted chasing it in labs.
But stay, be patient, one day you will see
It will be fucking understood by me.

Credit – Clarice Hong

O lentivirus – Lab Meeting 03/11/21

O lentivirus,
Will you please make more cells green,
Wonder what I’ll find.

Credit – Avinash Ramu

A puzzle – Lab meeting 03/04/21

Swapping out k-mers
Elements become too active
Small changes puzzle me

Credit – Mike White

Spot – Lab meeting 02/11/2021

See Spot run
See Spot scan
See Spot wait for exposing sites
See Spot bind
See Spot take
See Spot outcompete nucleosomes
See Spot spread
See Spot’s friends
See Spot create accessibility
See Spot wave
See Spot call
See Spot recruit transcriptional machinery
See Spot smile
See Spot cheer
See Spot reprogram to a happy lineage
Is Spot weird?
Is Spot cool?
No, Spot is just like all of the other transcription factors!

Credit – Jeff Hansen

Cell walls don’t crumble – Lab meeting 02/04/2021

Cell walls don’t crumble
DNA’s nowhere to see
Will Fluors light the way?

Credit – Kai Loell

One last thing before I go – 01/28/2020

chose artist’s home, for
science is self expression.
found beauty in truth.

This was Max’s last lab meeting with us. Max also shared some words of wisdom with us.

Words of Wisdom

  • Mentoring matters
  • Teaching will make you a better researcher and research will make you a better teacher
  • The goal of the lab is to help lab members get to where they want to go
  • Love people for their strengths and support them through their weaknesses
  • Science is a form of self expression
  • Trust your esthetic taste in problems and answers.

The student – Lab meeting 01/21/21

The student, she felt some distress,
That the QE could end up a mess.
She thought there’d be questions aplenty.
But the Profs’ heads were actually empty,
And the exam was a smashing success!

Credit – Barak Cohen

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Posts tagged #lab-meeting-poetry

What is this sequence – Lab meeting – 01/14/2021

What is this sequence–
Strong, silent, or inactive?
It’s all in the bits.

Credit – Ryan Friedman

Haiku was here – Lab meeting 12/17/2020

Haiku was here

From ashes of sparks,
Poets pick up left pieces,
“Hey! Poems were here”

Credit – Yawei Wu

If one sings about the invisible, and to Calvino – Lab Meeting 12/03/2020

If one sings about the invisible, and to Calvino
These cities Marco Polo told the Khan,
Which are forgotten by memory now,
Only shadows exist and else are gone.
Oh Where? In Levantine but no one saw.
Ooh! A human cries for joy not for pain,
Only in Diomera with damascened wall;
And Isidora, before her all fain,
In endless desires memory is all.
It’s real? The Great Khan asks, with his back bent.
Does it matter? As light as a feather
Polo’s answer is outside the present,
Just as daydreams, do not wither.
To feel the subtlety of foreverness,
And to kiss the pain of experience.

Credit – Siqi Zhao

Zoom – Lab Meeting 11/19/2020

Your face frozen on
my screen. These days we all have
limited bandwidth.

haiku by Janni Lee Simner, shared by Dustin

Brad – Lab Meeting 10/15/20

There once was a promoter called Brad
Who flew to a landing pad
He left in style
But landed in hell
He makes me a little mad

Credit – Clarice Hong

Jeff is a transcription factor – Lab meeting 09/24/20

Pursuit

Jeff biked off to find a good beer
But only closed breweries would appear
Good thing he was a pioneer developmental transcription factor
He broke in with his zinc retractor
And drank all the night with good cheer

Credit – Jeff Hansen

A TF ponders – Lab meeting 08/27/20

On the sense strand a TF pondered,
“Which way to the enhancer I wonder?”
Should I follow the loop,
through this phase separate soup?
Or hitch a ride with my pal p300?

Credit – Barak Cohen

A computationalist’s lament – Ryan’s lab meeting 8/20/20

Stay home? No problem! My work won’t be quenched.
After all, things in lab can make quite a stench.
But one fifty seven days
of work from home craze
makes me wish I did more at the bench.

Credit – Ryan Friedman

Mutants, brawn and bereavement from Nicole’s lab meeting – 8/13/20

There once was a zygote conceived
Whose genome mutated with ease
The mutations plopped on
With great strength and brawn
And now the parents are bereaved

Credit – Nicole Rockweiler

Haiku – Siqi’s lab meeting 7/30

Of those sleepless nights,
how many did you consume,
stochasticity?

Credit – Siqi Zhao

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Goodbye Ryan, Avi, and Kai!

The lab met at Barak's house to congratulate Ryan, Avi and Kai on their successful thesis defenses and wish them well in their next endeavors! Ryan will be starting a postdoc in Cole Trapnell's lab at UW, Avi will be joining the team at Verily Life Sciences, and Kai will be starting a postdoc in Justin Kinney's lab at CSHL.

Well done, Kai!

Congratulations to Kai Loell for bringing the Cohen lab defense record to 3/3 this week by successfully defending his thesis, "Biophysically-informed models of heterogeneity in transcription factor activity"! Watch a recording of the defense here.


Attachments

Congratulations Avi!

The second of three in this week's Cohen lab defense-o-rama — congratulations to Avi Ramu for successfully defending his thesis, "Sources and consequences of cell-to-cell variability in gene expression"! Watch a recording of the defense here.


Attachments

Congratulations Ryan!

Congratulations to Ryan Friedman for kicking off the Cohen lab's three-defense week by successfully defending his thesis, "Iterative machine learning of a cis-regulatory grammar"! Watch a recording of the defense here.


Attachments

Congratulations Clarice!

Congratulations to Clarice Hong for successfully defending her thesis, "Understanding gene regulation with high-throughput genome-integrated reporter assays"! Watch a recording of her defense here.

Summer Cookout — Goodbye, Jeff and Siqi!

The lab joined family and friends to celebrate Jeff and Siqi's successful defenses with a backyard cookout! Barak presented a book to each of the graduates, and everyone was treated to a magic show … um, I mean scientific demonstration of the power of ESP.

Congratulations Siqi!

Congratulations to Siqi Zhao for a successful defense of his thesis, “Single-cell massively parallel reporter assays”, completing the Cohen lab June thesis defense double-header! Watch a recording of his defense here!


Attachments

Congratulations Jeff!

Congratulations to Jeff Hansen for a successful defense of his thesis, “A Test of the Pioneer Factor Hypothesis for Silent Gene Activation”. Watch a recording of his defense here. Jeff is an MSTP student and will be returning to the clinic for the final two years of Medical School, so we still hope to see him around!


Attachments

One last thing before I go – 01/28/2020

chose artist’s home, for
science is self expression.
found beauty in truth.

This was Max’s last lab meeting with us. Max also shared some words of wisdom with us.

Words of Wisdom

  • Mentoring matters
  • Teaching will make you a better researcher and research will make you a better teacher
  • The goal of the lab is to help lab members get to where they want to go
  • Love people for their strengths and support them through their weaknesses
  • Science is a form of self expression
  • Trust your esthetic taste in problems and answers.

Back to back to back!

Congratulations to Clarice, to Siqi, and to Jeff on successfully proposing their theses! The three have hitched their wagons together so as one wagon advances ahead, the others are pulled alongside. In such a way, the three have boosted each other’s science and buoyed each other’s spirits. A regular Cerberus of science. What a team!

We look forward to seeing what comes out of each one’s thesis work.

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Reflection upon a passed qualifying exam

Today in lab we were calling each other “champ”. My mom calls me Jeff. I passed my qualifying exam last Friday. Instead of providing you the blow-by-blow of my lively discussion on what sequence features determine pioneering activity, I will reflect. I hope to convey how positive an environment a lab can be.

As an MD-PhD student, I completed two years of classroom medical school prior to starting my PhD. During those first two years, I took many exams. Each exam was a real battle – from memorizing each drug used to treat heart failure to understanding how the kidney uses a litany of channels to filter our blood. By design, these two years were me against the knowledge base. Indirectly though, it was me against my classmates as we vie for a limited number of spots in competitive specialties. The result was that at times the crushing individualism led to lonely isolation.

What a difference the Cohen lab has been. A tradition of committing ourselves to each others’ crafts defines the lab, and defines the research environment at WashU. As my talk rose on the horizon, my lab mates gathered around our cozy conference table and spent hours helping me hone my ideas and sharpen my arguments to send me towards my QE. And as I stepped out of the room as my committee deliberated, there was Clarice down the hall with a wide grin on her face welcoming me back into the arms of the lab.

While the day-to-day life of medical and graduate school differ greatly, each focuses on the pursuit of knowledge. In my experience, one goes about that individually and one goes about that collaboratively. And I thank the cloning gods above that I found myself amongst the champs of Barak’s lab.

Farewell, Hemangi!

On Sunday, Barak hosted a farewell brunch for our senior graduate student, Hemangi Chaudhari. Beyond her contributions to the scientific community, Hemangi has provided wisdom and guidance to our lab for several years now. To the younger graduates, she provided patient instruction. To her classmates, she provided unbeatable cuisine and loyal companionship. And to post-docs and PIs, she provided an intellectual debate over the implications of a result or the design of an experiment.

As Hemangi moves to Boston, we wish her the warmest farewell. As she leaves behind her pipettes (to be scrounged after by incoming students) she leaves a lasting mark on both the lab and the scientific trajectories of those that were lucky enough to spend time with her in St. Louis. We all hope to cross paths again soon, as we crisscross through scientific communities all pointed towards a greater understanding of biology. While the farewells may be blue, the difficulty in parting demonstrates how strong the connections developed to be.

Farewell, Hemangi! We’ll see you again soon!

Image: Masala dosa – featured at the farewell brunch – every bite cherished (source: NY Times).

Qualifying Exam Successes

Congratulations to Clarice Hong (Molecular Genetics and Genomics) and Siqi Zhao (Computational and Systems Biology) on passing their Qualifying Exams!!! They have their wagons hitched to a star and we can’t wait to see where their scientific adventures travel next.

Hemangi’s Thesis Defense

Our intrepid landing pad explorer has successfully defended her thesis, titled “Integration of local and regional regulatory information in the human genome”!!!

Afterwards, we toasted champagne and had delicious Himalayan Yeti as we recounted Hemangi’s many wonderful accomplishments.

Mike White promoted to Assistant Professor

We are pleased to announce the Mike White PhD has been promoted to the rank of Assistant Professor of Genetics. This is well deserved. It is expected that Mike will continue his own research with the added distractions of worrying about grants, sitting on useless committees, and teaching classes to recalcitrant graduate students.

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Cohen Lab attends ASBMB meeting

Mike, Clarice, Ryan, Kai, and Yawei recently traveled to the Stowers Institute in Kansas City to attend the ASBMB conference "Evolution and Core Processes in Gene Expresson". Clarice gave a talk and everyone else presented a poster. Congratulations to Yawei, who was awarded a Best Poster Award for a graduate student!

We had a great time learning about the latest research in cis-regulatory grammar, enhancer evolution, and predictive models of gene regulation. We also enjoyed eating some delicious Kansas City BBQ and connecting with our peers and colleagues in the field.

Listen to Barak’s Podcast with Shelina!

You can listen to the podcast here.

Brett Maricque, interviewed on “St. Louis on the Air”

Graduate student and current BALSA president, Brett Maricque, and co-founder, Maxim Schillebeeckx, discuss how the BALSA group allows graduate students to gain business experience while providing quality, low cost consulting services for the growing St. Louis biotechnology sector and generating grant money for local entrepreneurs through the BALSA Foundation. Listen to the full conversation on the “St. Louis on the Air” website.

Mike White interviewed in St. Louis Magazine

Our own Mike White talks about what makes genetics cool in an interview for St. Louis magazine.

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Fourth Cohen Research Conference

The fourth annual Cohen Research Conference was held October 23-25, 2023 in Michigan City, IN. Lab members presented talks on big ideas or out-there experiments. Continuing the tradition from prior CRCs, we also enjoyed communal cooking, a campfire near the lake, and a dunes hike in Indiana Dunes National Park which passed through Cowles Bog, a site of seminal research on ecological succession!

Third Cohen Research Conference

The third annual Cohen Research Conference was held October 17-19, 2022 in Cadiz, KY. Everyone presented a talk about big questions or ideas they have. We also enjoyed communal cooking, a campfire near the water, a hike through the Land Between the Lakes National Recreation Area, moonshine tasting, puzzles and board games, guitar performances by Barak and rotation student AJ, and more! We also stopped in Metropolis, IL to see a 15-foot statue of Superman. A great time was had by all. The CRC has certainly been cemented as a lab tradition!

Photo credit: James

New Paper from the Lab

Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats Kai!

Papers from the lab

Ryan, Max, Clarice and Jeff all had papers published recently! You can find the links to the papers in the Publications section.

Shown above are cool illustrations that describe Clarice's and Jeff's papers. Can you spot the molecular players in these?

Second Cohen Research Conference

The second Cohen Research Conference was held September 13-15, 2021 at Lake Geneva, WI. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board games, swimming and kayaking, a lakeside hike, a meditation session, science talks out on the deck, and more! A strong continuation of CRC tradition. Thanks to Clarice and Jeff, the chief organizers of the conference.

Gene regulation and fruit from a tree – Yawei’s lab meeting 8/7/20

Yawei started lab meeting with a cartoon depicting a model of gene regulation. See if you can figure out the analogy.

Image credit – Yawei Wu

First Cohen Research Conference

The first-ever Cohen Research Conference was held Feb 25-27, 2020 at Stonehaven Castle, Eureka Springs, AR. Every conference attendee registered online for the conference and presented a talk. Other activities included communal cooking, board-games, day-time and night-time hikes, a meditation session, sciencing around a campfire, spotting constellations on a clear black sky, balancing the entire lab on a log, and impromptu midnight performances with the guitar by Barak. It was a truly special experience. Thanks to Clarice and Jeff, the chief organizers of the conference.

Photo credit: James

We do science, too

We have a lot of fun in the Cohen Lab. We sail, and we eat donuts, and we brainstorm big ideas over tasty cocktails. But at core, we are a band of renegades, uncovering secrets of the genome. The only evidence for that claim that you’ll need is the picture below, showing Max and Maria and Clarice taking care of their cells, on a Cohen-Triple-TC-Hood-Combo-Day.

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