Lucas Herissant is a CEHG postdoctoral fellow in the lab of Gavin Sherlock in the Department of Genetics. Lucas received his Master’s degree in Genetics from the University Paris Diderot – VII in France. He joined Catherine Dargemont’s lab in the Jacques Monod Institute (IJM, University Paris Diderot – VII, France) where he completed his PhD. His research focused on the role of Histone H2B ubiquitination in mRNA maturation. Here in Gavin Sherlock’s lab, his research focuses on the prevalence of antagonistic pleiotropy, using experimental evolution to generate adaptive mutants and investigate their pleiotropic effect.
This content has been transcribed from an interview that took place on Stanford campus Wednesday, October 21, 2015 with CEHG’s Director of Programs, Cody Montana Sam and Communications Manager, Katie M. Kanagawa.
Can you start by telling us a bit about your research?
I did my PhD in Paris, France. I did mostly histone modification and mRNA synthesis and maturation. I have especially focused on the next step of transcription, which is the maturation of mRNA and the recruitment of other proteins on the mRNA. We showed that if a set of proteins isn’t present, then the mRNA is less efficiently spliced or matured and then it is not exported in the cytoplasm for translation. If there is no good cycle of ubiquitination/deubiquitinqtion of the H2B histone, there is no good recruitment of the protein to make the mature mRNA ready to export.
So you came to Stanford to work on Antagonistic Pleiotropy. Can you tell us a bit about that?
Pleiotropy is when there’s one gene that goes with two phenotypes and antagonistic is when there is both a detrimental and a beneficial effect.
I wanted to do something different from my PhD, but keep something similar, so I kept the yeast model organism but changed the topic to do genetics. I wanted to learn to do computational work, so I came to Stanford to do that.
What would you say motivates your work in biology and genetics? In particular, what draws you to genetics and pleiotropy in particular?
For me, the reason I was interested in biology was that when I was a kid, my mother explained to me why I got blue eyes when both my parents have brown eyes. That was something that rang a bell for me.
When I was in high school in France, I was kind of a lazy student but I always had good grades in biology. That was where my interest was anyways, so I figured I might as well go for that [laughs]. So I just continued to do that.
But now, with antagonistic pleiotropy, I would say that Gavin proposed it and I was happy to pursue it. It has opened up for us an opportunity to understand the interaction between different mutations and the environment and what could be the positive effect of that kind of mutation.
What are some examples of antagonistic pleiotropy?
We don’t study one specific case. What we do is evolve yeast cells in 12 different conditions so they adapt and gain beneficial mutations. Then, we grow the adapted cells in all other conditions and look at the fitness in those other conditions. If the fitness is lower than a reference wild-type cell, then the adapted clones show antagonistic pleiotropy in this specific other condition. We characterize the mutation that these cells carried.
What is it like working with your previous advisors, Gavin [Sherlock] and Catherine Dargemont?
They are opposites. My previous boss, Catherine, knew every day what I was doing. Every experiment I did, she knew it. She had an idea of when I should get a result on a daily basis. She was very hands on. Gavin is the opposite, just do what you want to do or what you have to do. We try to meet on a weekly or bi-weekly basis. It is really the difference between PhD and postdoc study.
Can you tell us a bit about your parents’ background? How did they influence your decision to pursue a career in science?
All of my family members are wheat and corn (crops) farmers. Growing up, I wasn’t into farm stuff at all, whereas my brother was really into it. I think, at some point, I rejected that. I could have done vegetable biology, but I chose to do something else.
What would you say is next for you, maybe 5 or 10 years down the road?
It’s not clear yet. I’m just going to enjoy my postdoc for the moment. I’ll maybe think about that next year. The question of whether I want to be a professor or work in industry, and whether I want to go back to France or stay here or go somewhere else, I don’t know.
What would you say are the differences between the US and France?
It’s a bit hard to say because my only experience in the US is Stanford, but it’s been perfect. Here, we have a lot of great tools with great people who will try to help you and give you advice and ideas.
Do you have any advice for people in your position, who are coming to the US for the first time to study genetics or may be considering pursuing a career in genetics?
Have a large pallet of skills, because I was lacking computational skills and that was necessary. Make yourself adroit.
Have good English. At some point, I had an issue with that.
You said you were learning Python Scripting and computational work. What classes are you taking?
I took Gavin’s genomics class (GENE211). I tried to follow Andrew Fire’s Python class (GENE218); I didn’t get to attend all of it, but I have all the papers.
Has there been one person who has had the biggest impact on your career?
Can I say my wife? Because I was doing my undergrad study in another city and then I met my wife who was in Paris, so I decided to find a PhD lab there. I wasn’t sure I wanted to do a postdoc, but we thought we wanted to go to another country and experience something else. So, here we are.
My wife and I have been married 2 ½ years. We married in France, and we’re having a baby, due in February 2016.
[Update since fall 2015 interview: Lucas’ baby girl, Joséphine, was born on February 19, 2016. Congratulations to the new dad!]