<aside> 🔬 I am fascinated with life. My scientific interest in biology is perhaps unsurprising then. However, I have never been a one subfield kind of gal. I have done work ranging from studying basic protein synthesis to decoding fruit-fly genomes to understanding the communication between gut microbes and human cells. Here’s a glimpse of some of the science I have done/am doing that I am most jazzed about and the wonderful people that are part of my scientific journey.
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Jost Lab, Harvard University
2021 - Present
Why should you care? Trillions of microorganisms call our guts home. A lot of work has shown that out gut microbiomes are essential to our overall health. We know that if our gut microbiomes are significantly disturbed, we are more likely to get autoimmune and inflammatory disorders. So understanding how our microbes maintain balance within our gut is essential to help us stay healthy.
What do I study? Our gut microbes communicate with our cells that make up the gut as well as with organs that are far away from the gut such as the brain. This communication is facilitated by the production of small molecules — these can be derived by breakdown of our food, for example. These small molecules can enter our bloodstream and reach distal parts of our bodies and influence our physiology. I am interested in how human cells across the body recognize these small molecules and know how to mount specific responses to them.
The nitty gritty: My project is focused on a specific mode of small molecule recognition: the aryl hydrocarbon receptor (AhR). This transcription factor is super cool because it can recognize many different molecules that look completely different from each other. AhR can be found in all sorts of human cells including the liver, the brain, the kidney, and immune cells. But, it doesn’t respond to the same microbial molecules in all these cells. This is the conundrum that I’m interested in solving. Using chemical screening methods, I am developing a broader understanding of AhR’s cell-specificity. My goal is conduct functional genomics to understand specific mechanisms that allow AhR to be picky in terms of which molecules it recognizes in which cell types.
If you think this is cool, you can check out the Jost Lab!
Jost Lab at Cape Cod, MA, 2022
The first Jost Lab retreat in New Hampshire, 2022
Chip taste-test at the 1st Jost Lab holiday party, 2021
Djuranovic Lab, Washington University in St. Louis
2017 - 2020
Why should you care? Proteins are the workhorses of our cells. They are responsible for pretty much all functions that occur in cells whether that be enzymatic reactions to break down nutrients or controlling which genes turn on and off in response to some stress. In addition, synthesizing protein is key in pharmaceutical industries, think insulin. There is thus a great need to understand how protein can be synthesized most efficiently.
What did I study? My project in the Djuranovic lab focused on understanding whether there were certain sequences of RNA that the ribosome could read more efficiently than others. If yes, what were these sequences? This work was following up on an interesting observation made in the lab before I got there that suggested that making minor sequence changes could change how much protein is produced quite drastically.
The nitty gritty: This project revealed that in a given protein sequence, amino acids 3 to 5 are crucial in dictating how efficiently the protein will be synthesized. We figured this out by generating a library in E. coli where we tried to generate every possible combination of amino acids 3 to 5 (or more specifically, RNA sequence 6 to 15) for the GFP gene. GFP codes for the green fluorescent protein which fluoresces green and can thus be used as a way to detect how much protein is being produced. The greener it is, the more protein there is. We used flow-cytometry based sorting to collect the sequences that caused the signal to be greenest and worked with various collaborators to determine that it was the ribosome stalling on certain sequences that resulted in less protein production in those cases.
I wrote my senior undergraduate thesis on this work and was awarded the Spector Prize for best Biology thesis. If you think this work is cool, you can check out the Djuranovic Lab & our publication on this work!
Djuranovic lab grabbing lunch in St. Louis, 2019
WashU’s Undergraduate Research Symposium, 2019
Djuranovic Lab reunion, 2022 ft. Sergej’s excellent grilling
© 2022 Manasvi Verma.