Sourav Bandyopadhyay

@byersblake How about low dose epinephrine? Activates ADRB1. I bet that will keep you awake

A few friends and I are going to fund a $400k research study on whether we can get a taste of this superpower for everyone. We have some friends that run a gene editing lab at Harvard who are willing to run the experiments. Key points to validate: (1) Determine at what stage of organism development you need to intervene to get the superpower. We know having these mutations from birth gives you sleep superpowers, but if you edited someone as an adult, would they get equal benefit or is there something about the wiring of your brain during development that is required? And when in development? embryonic, toddler, teenage? Need to run some studies in animals to figure this out. (2) Some of these short sleeper genetic variants my be easier to drug than others (with RNAi, epi editors, base editors, etc). So we need to run some quick experiments to select which are optimal.

@london_lab Awesome!

Combining covalent chemistry with proximity inducers expands their scope, and drives new discoveries. I tried to capture the state of the field in this (open access) comprehensive review. Good news - there are plenty of opportunities up for grabs :) pubs.acs.org/doi/10.1021/ac…

@byersblake Editing not necessary. ADRB1 is the beta andrenergic receptor, agonists already out there. en.m.wikipedia.org/wiki/Beta1-adr…

There are people who genetically only need 4-6 hrs of sleep per night. They also "tend to be more optimistic, more energetic and better multitaskers. They also have a higher pain threshold, don’t suffer from jet lag and some researchers believe they may even live longer." We know this can be driven by a single mutation in the gene ADRB1. I need someone to hurry up and make a gene editor so I can get a taste of this freedom. To frame the upside here: in 80 years of life, you sleep for ~20 years. Short sleepers only sleep for ~10 years. Thats +10 years of awake life! Insane life alpha.

Congrats to the Vividion team on a KEAP1 binder which unexpectedly turned out to be a KEAP1/CUL3 molecular glue to degrade NRF2. Unexpected activity since known binders inhibit KEAP1 rather than activate. Kudos to sticking with the data and expecting the unexpected! link below

Doing good science is 90% finding a science buddy to constantly talk to about the project.

Your welcome! Hope your well

I have benefited greatly from some amazing books that helped define my approach to science, startups and leadership. Delighted to pass them on! 1/5

The Biotech Leaders Handbook by Angelos Georgakis. A wonderful summary of so many biotech leadership and fundraising books and interviews with leaders in the space. Great set of cliff notes, with wide ranging topics from managing conflict to raising money. Enjoy! 5/5

Hard Thing About Hard things by Ben Horowitz. Best encapsulation of the vision, dedication, and perseverance that a founder needs to have to be successful. Written for tech, but this vital information is applicable in any industry 4/5

First up Emperor of All Maladies by Siddharta Mukherjee. Amazingly written and captivating piece of the history of mankind’s battle with cancer. For me, so elegantly put our research into a broader context that it inspired me to double down my focus on cancer therapies 2/5

A feature in @NatureBiotech discusses the rise in team size in academic science and how it has generated an unintended side effect: junior scientists are less likely to secure research funding or obtain tenure and are more likely to leave academia. 🔒 go.nature.com/4dtPTx1

@KRHornberger Thanks for all the wisdom Keith! If the drug is 98.4% bound in plasma wouldn’t it be similarly bound with 10% FBS in cell culture? I wondering how necessary is this step of calculating free drug when both in vivo and cell culture seem to be the same

(Aside #2: this is actually a conservative estimate. If you read the experimental, the cells are cultured in 10% FBS and we’d expect nonspecific compound binding to the assay media to reduce free drug in the cell assay below the dosed concentrations.) 11/

Let’s dig in a little more on this paper and why I liked it. One of its strengths is that all the in vivo data hangs together and tells a sensible story in a way that many other papers do not. More below! 👇 1/

Congrats to Mauricio Jacobo Jacobo and Hayley Donnella who drove the project and have both moved on from the lab and thanks to our wonderful collaborator @AndreiGoga_SF @UCSFCancer

We also found in vivo and clinical evidence that cGAS signaling leads to poorer outcomes in breast cancer treated with chemo

In what started as a control experiment we were surprised to find transcriptional heterogeneity even in cancer cell lines, in ways that make certain subpopulations resistant to standard of care tx. nature.com/articles/s4159…

Its been thrilling to see Rezo hitting its stride in mapping networks, prosecuting targets and drilling into drug discovery. Amazing things to come. We are excited to build the NextGen Sequence->Systems->Structures->Drugs platform!

Great department and wonderful place to start your career!