Meet a Whitehead Postdoc: Brian Abraham

Brian Abraham is a computational biology postdoc studying the role of DNA transcription in human health and disease in Whitehead Member Richard Young's lab. He held the Hope Funds for Cancer Research Grillo-Marxuach Family Fellowship from 2015-2018. Abraham is passionate about science outreach and has participated in LabTV, NOVA Science Cafe, and the Cambridge Science Festival. He can be found on twitter @snarkyscientist or blogging about science and life therein at SnarkyScientist.com. We sat down with Abraham to learn a bit more about him and his experiences in the lab.

What do you investigate?

I investigate how different cells differently interpret the same instructions in DNA.  The differences can be in the behaviors or jobs of two healthy cells, a healthy or diseased form of the same cell, or in the DNA itself in the form of a mutation. How these DNA instructions are interpreted by cellular machinery in a process called DNA transcription is what give healthy cells their characteristics and helps diseased cells cause problems.

 
As a computational biologist, what is your role in the lab?

The Young lab builds small teams to tackle our projects efficiently. We believe team science benefits the research, the scientists, and the community because different researchers enjoy and excel at different things, and the research is done more expediently. As a computational biologist, I'm a member of many of these teams and, unlike my teammates, my skillset is entirely computer-oriented. Much of my job involves getting yes/no/maybe answers to biological questions the team is interested in by staring at my computer screen and building graphs and figures based on data generated from “wet bench” lab experiments to test them. I write code to take datasets generated by my labmates or the research community and distill key takeaways from their data points. This lets us generate hypotheses and test them quickly as well as find out how broadly our conclusions apply.

How did you get started in this field?

Accidentally. I went to college to learn to build websites, but realized it wasn't for me, and I needed to pivot. I had always had an interest in genes and DNA (at least partly due to Jurassic Park), and I saw an opening in my hometown of Buffalo, New York at the Roswell Park Cancer Institute for a summer research internship. I took it. It involved sitting in a nearly windowless room with three computers and two other coders and comparing the then-two genomes that had been sequenced against each other. It was a tedious, small project but I was hooked and I signed up for the GRE and hunted grad schools during the last few weeks of that internship.

As a kid, what did you think you were going to be when you grew up?

Kindergarten me would have said "hockey doctor" after I realized that the team physician for the Buffalo Sabres was listed in the game programs.

What part of your research is the most fun to do?

Fast-walking through the lab to find someone whose data just turned into a neat result on my computer screen to tell them what it is and what it means. It's really fun being the only person in the world to know something, but I try to make that group bigger as quickly as possible.

One interesting finding I discovered came about by just chasing down an intellectual itch that I wanted to scratch. For some time, investigators have been arguing that transcription factors—proteins that control the levels of production from genes—usually can directly turn genes both on and off. This was inconsistent in my mind with the lab's work demonstrating that the oncogenic transcription factor c-MYC seemed to only activate gene expression. I found myself wondering if other types of transcription factors, not just c-MYC, only activate or only suppress. My collaborators had coincidentally generated the exact data I needed to answer this question: They shut down production of another transcription factor, MITF, and measured expression of all the genes in the genome. The result was clear: Loss of a "master" transcription factor could lead to the same loss of gene expression seen with the oddball c-MYC. When I found this out, I brought a few labmates over to my desk to show them some figures I'd made demonstrating this result and we started pitching new projects inspired by my results.

What’s the biggest thing you’ve broken?

Sometimes my attempts at efficiency backfire in unexpected ways. I once submitted 6.78 million jobs to the computational cluster in a month. Nearly all of them completely failed. I was trying to quickly determine if 100,000 mutations I predicted in tumor genomes existed and/or altered the genes a given tumor cell used. I broke those 100,000 mutations into a job apiece and wrote a bad loop that submitted them a few hundred times apiece. That quickly got the attention of the IT team at Whitehead, who kindly suggested alternative code structures that had the problem solved in a week.

What inspired you to start your blog (Snarky Scientist)? What do you enjoy about communicating science to non-scientists?

I was the first in my family to go away to college, so talking to my family about what I do has always been a challenge. Because of my stumbling toward a scientific career, I remember what it's like to not know anything about biology or genes and DNA. Yet, we regularly ask people whose last biology class was 30 years ago using books then-30 years out of date to vote for representatives who make decisions on how scientists advance things like GMOs and cloning. This inspired me to try to bridge the gap between the interested and the knowledgeable. I get particularly excited about being in front of people because, while there's a glut of amazing science writing out there, in person meetings or just seeing someone on screen can help non-scientists develop trust in science. And there's nothing quite like watching someone understand something amazing for the first time.

What’s the latest you’ve ever been in the lab? What were you doing?

I overnighted in the lab once, so a full 24-hour day. I was trying to finish a paper before going home for the holidays and had realized the day before that I needed to completely remake all of the figures. An early step in my analysis had been done badly. I was trapped on campus once the Metro shut down, so, after finishing around 5AM, I crashed on the lab couch and woke up when people started coming in for the day.

Where do you see yourself in 10 years?

Balancing running a small lab with a side hustle bringing scientific understanding to non-scientists (normal people) through podcasts and town halls. Also having dogs.