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.
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.
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!
Masala dosa – featured at the farewell brunch – every bite cherished
(Source: NY Times)
Sometimes we have a hard time figuring out where in the genome transcription factors prefer to bind. Cheeky little fellows. Our esteemed Hemangi Chaudhari was not having it. She took up her mighty pipette and worked to figure out what features reside in the flanking regions of TF binding sites that might define either high or low expression. Check out her publication that just came out in Genome Research, titled “Local sequence features that influence AP-1 cis-regulatory activity”. Great job, Hemangi!! (https://genome.cshlp.org/content/28/2/171.abstract)
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 idea’s 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 Idea’s 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.