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Use the links above to return to the Cohen Lab homepage or another section.
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
No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.
Credit – Yawei Wu
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
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,
Will you please make more cells green,
Wonder what I’ll find.
Credit – Avinash Ramu
Swapping out k-mers
Elements become too active
Small changes puzzle me
Credit – Mike White
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
DNA’s nowhere to see
Will Fluors light the way?
Credit – Kai Loell
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
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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–
Strong, silent, or inactive?
It’s all in the bits.
Credit – Ryan Friedman
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
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
Your face frozen on
my screen. These days we all have
limited bandwidth.
haiku by Janni Lee Simner, shared by Dustin
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
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
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
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?
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
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
Of those sleepless nights,
how many did you consume,
stochasticity?
Credit – Siqi Zhao
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
You can listen to the podcast here.
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.
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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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!
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.
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.
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.
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.
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!
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!
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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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.
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.
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.
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.
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.
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.
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).
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.
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.
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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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.
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.
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 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.
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
Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats Kai!
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 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!
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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Cohen Lab
Couch Biomedical Research Building
CAMPUS BOX #8510
4523 CLAYTON AVE
SAINT LOUIS, MO 63110
Office: 314-362-3674
Lab: 314-362-3679
Fax: 314-362-7855
cohen [at] wustl.edu
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.
The Cohen Lab is currently seeking motivated postdocs. Interested applicants should contact Barak with a cover letter and CV.
2023-10-23 | Fourth Cohen Research Conference |
2023-05-29 | Goodbye Ryan, Avi, and Kai! |
2023-05-09 | Well done, Kai! |
2023-05-04 | Congratulations Avi! |
2023-05-02 | Congratulations Ryan! |
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.
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]
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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.
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.
O lentivirus,
Will you please make more cells green,
Wonder what I’ll find.
Credit – Avinash Ramu
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.
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.
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
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
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.
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.
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.
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.
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.
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.
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
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
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.
Your face frozen on
my screen. These days we all have
limited bandwidth.
haiku by Janni Lee Simner, shared by Dustin
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).
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
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!
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
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.
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.
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!
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.
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.
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.
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.
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 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.
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
Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats Kai!
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.
Congrats James for recieving a F30 award from NEI for the project "Multiplex functional assay of variant effect in the retinal transcription factor CRX".
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!
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
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
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
Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats 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.
Cell walls don’t crumble
DNA’s nowhere to see
Will Fluors light the way?
Credit – Kai Loell
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
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.
Great work Max for recieving a K99 award from NIGMS for his project "High-Throughput Functional Interrogation Of Mammalian Activation Domains".
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.
Swapping out k-mers
Elements become too active
Small changes puzzle me
Credit – Mike White
Our own Mike White talks about what makes genetics cool in an interview for St. Louis magazine.
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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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!
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!
Congrats James for recieving a F30 award from NEI for the project "Multiplex functional assay of variant effect in the retinal transcription factor CRX".
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
Genome
Genetics
Phonetics
Photon
Roton
Rotor
Motor
Money
Honey
Bunny
Bagel
Kegel
Candy
Dandy
Dandruff
Beard scruff
Beer
Fear
Deer
Donuts
Credit – Jeff Hansen
No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.
Credit – Yawei Wu
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
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,
Will you please make more cells green,
Wonder what I’ll find.
Credit – Avinash Ramu
Swapping out k-mers
Elements become too active
Small changes puzzle me
Credit – Mike White
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
DNA’s nowhere to see
Will Fluors light the way?
Credit – Kai Loell
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
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–
Strong, silent, or inactive?
It’s all in the bits.
Credit – Ryan Friedman
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
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
Your face frozen on
my screen. These days we all have
limited bandwidth.
haiku by Janni Lee Simner, shared by Dustin
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
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
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
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?
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
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
Of those sleepless nights,
how many did you consume,
stochasticity?
Credit – Siqi Zhao
Congrats Ryan for recieving a F31 award from NHGRI ("Interpreting function of non-coding sequences with synthetic biology and machine learning").
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
Great work Max for recieving a K99 award from NIGMS for his project "High-Throughput Functional Interrogation Of Mammalian Activation Domains".
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
You can listen to the podcast here.
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.
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.
Our own Mike White talks about what makes genetics cool in an interview for St. Louis magazine.
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.
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.
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.
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?
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.
Congrats Ryan for recieving a F31 award from NHGRI ("Interpreting function of non-coding sequences with synthetic biology and machine learning").
What is this sequence–
Strong, silent, or inactive?
It’s all in the bits.
Credit – Ryan Friedman
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
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.
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.
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!
Of those sleepless nights,
how many did you consume,
stochasticity?
Credit – Siqi Zhao
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
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.
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
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.
No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.
Credit – Yawei Wu
Haiku was here
From ashes of sparks,
Poets pick up left pieces,
“Hey! Poems were here”
Credit – Yawei Wu
* These authors contributed equally to this work.
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
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]
Chen CTL, Gottlieb DI, Cohen BA Ultraconserved Elements in the Olig2 Promoter. PLOS One (2008) [doi: 10.1371/journal.pone.0003946]
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]
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]
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]
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.
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:
We are developing a suite of experimental technologies to design, construct, and assay tens of thousands of reporter genes in a single experiment.
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.
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.
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.
We are investigating how stochastic fluctuations in gene expression can inform on the mechanism enhancers use to activate gene expression.
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.
We are developing a suite of experimental technologies to design, construct, and assay tens of thousands of reporter genes in a single experiment.
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.
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.
We are investigating how stochastic fluctuations in gene expression can inform on the mechanism enhancers use to activate gene expression.
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.
Unique Barcode Integration Calculator — A tool to help investigators design barcoding schemes for massively parallel genome-integrated assays.
GitHub — The Cohen Lab GitHub account with any public code accompanying manuscripts.
Lab Wiki — An internal wiki for lab members (login required).
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.
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 for recieving a F31 award from NHGRI ("Interpreting function of non-coding sequences with synthetic biology and machine learning").
Great work Max for recieving a K99 award from NIGMS for his project "High-Throughput Functional Interrogation Of Mammalian Activation Domains".
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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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.
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.
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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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!
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.
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.
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
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.
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?
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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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.
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.
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.
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.
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
No leaves get exact twins
Flow never sees the same drops
Careful! Details kill.
Credit – Yawei Wu
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
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,
Will you please make more cells green,
Wonder what I’ll find.
Credit – Avinash Ramu
Swapping out k-mers
Elements become too active
Small changes puzzle me
Credit – Mike White
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
DNA’s nowhere to see
Will Fluors light the way?
Credit – Kai Loell
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
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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What is this sequence–
Strong, silent, or inactive?
It’s all in the bits.
Credit – Ryan Friedman
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
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
Your face frozen on
my screen. These days we all have
limited bandwidth.
haiku by Janni Lee Simner, shared by Dustin
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
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
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
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
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
Of those sleepless nights,
how many did you consume,
stochasticity?
Credit – Siqi Zhao
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.
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.
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.
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.
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.
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!
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!
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
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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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.
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).
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.
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.
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.
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.
You can listen to the podcast here.
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.
Our own Mike White talks about what makes genetics cool in an interview for St. Louis magazine.
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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!
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
Kai's paper about how transcription factor activation domains regulate gene expression noise is out in Cell Reports. Congrats Kai!
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.
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 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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