Conversations with Lipid Leaders: Dr. Bruno Antonny
Tell us a little bit about yourself (current role, background, family, etc.)
I grew up in the alps area in France. I was interested in science in general but with no strong inclination for biology. At the age of 18, some of my friends decided to continue in Maths, Physics, or Business. I decided to go for biology to do something different. I started enjoying molecular mechanisms, so I opted for biochemistry. Since then, my journey in Science has been a mix of luck and decisions; luck to meet some great scientists like M. Chabre, my PhD advisor; decisions, when I quitted phototransduction for membrane traffic, or when I decided to do experiments with liposomes.
Did you always envision yourself becoming a scientist? If not, what did you want to be when you grew up?
My grand-parents were employees in the textile industry, my mother was a secretary who then took care of her four children, and my father was an engineer in a factory. If there was a lot of respect for science in the family, I was not exposed to the lab and academia milieu, and doing science was just among the few dreams I had, including becoming a ski teacher.
Who influenced you to become a scientist?
In 1988, while looking for a lab to finish my undergrad studies, I had a chance to attend a seminar of Marc Chabre, who was a leader in the field of phototransduction. The way he was doing science was illuminating; setting up original real-time assays to dissect one of the most efficient signaling cascades in our body. When he interviewed me as a prospective graduate student, he did not care so much about my knowledge but inquired whether I had good hands and could solve problems. He valued students who were capable of repairing their cars, which was not my case. He was an amazing but very demanding mentor, a kind of Lieutenant Columbo, with exceptional reasoning to solve biochemical puzzles.
In 1998 I attended my first conference on membrane traffic. The lecture that Randy Schekman gave there was the second turning point of my career. His lab had just succeeded in reconstituting on synthetic liposomes the assembly of a protein coat, a minimal molecular machinery that forms transport vesicles. I contacted him, asked whether I could join his lab to dissect this reaction, and he said yes.
What do you consider the greatest breakthrough in lipid research in recent years?
The discovery of lipid remodeling enzymes, notably by the Shimizu lab in Japan because it opens an avenue for understanding how and why cells in real tissues control so well the acyl chain profiles their organelles. Classical cell lines used by cell biologists are very rudimentary in this respect.
What was your inspiration for investigating the interplay between proteins and lipid membranes?
In 1995, I started working on a small G protein named Arf1. I was interested in its striking ability to bind lipid membranes in a GTP-dependent manner but I was not satisfied by the way this mechanism was studied. Reading the work of two excellent biochemists J Silvius and S McLaughlin convinced me that I should learn how to make decent liposomes. I borrowed a rotary evaporator, started doing my first orders to Avanti, and our workshop built a hand extruder as this apparatus was not commercially available at that time. We also set up superior assays to follow the GTP switch of Arf1 on membranes. Thanks to these efforts and to great collaborators including Dan Cassel, Pierre Chardin, Jacqueline Cherfils, Cathy Jackson and Anne Peyroche, we succeeded in understanding the way Arf switches between GDP and GTP-bound forms at the membrane surface upon the action of exchange factors and GTPase Activating Proteins.
Which of your research projects or findings have you found most interesting? Why?
My lab has made three main discoveries: (i) membrane curvature is cellular information, (ii) PI(4)P is a cellular currency for the transport of other lipids; (iii) polyunsaturated lipid facilitate membrane deformation. I would like to quote here a work linked to the third discovery, in which we addressed a very old question: why are most biological lipids asymmetric in their acyl chain composition? Using comprehensive series of lipids with a well-defined acyl chain composition (some custom-made by Avanti), we discovered that natural lipids with one saturated and one unsaturated acyl chain solve the conundrum of having membranes that are both efficient barriers to solutes and capable of deformation and fission*. These are two essential functions for cell life. Of note, DOPC, which is still largely used as a cheap background lipid in biochemical reconstitutions, is not the best biological lipid species considering the balance between these two properties.
Your research indicates that PI(4)P acts as a “lipid form of ATP” by OSBP. Can you explain what this means and how PI(4)P acts as metabolic energy in this case?
A few years ago, we discovered that two cytosolic proteins, Osh4 in yeast and OSBP in mammalian cells, can extract two lipids that are chemically very different: cholesterol and PI4P. This was counter-intuitive from a structural point of view but functionally very exciting. We envisaged that, in the cell, the two lipids might not compete but be exchanged between membranes. We could test this hypothesis in cells and showed that PI(4)P serves as metabolic energy for the directional transport of other lipids. To transport one molecule of cholesterol, the cell needs to transport one molecule of PI4P in the other direction and burn it, hence the idea that PI(4)P acts as a lipid form of ATP.
What are your hobbies? What do you like to do outside of the lab?
I’m fond of Judo and skiing. I also like playing the guitar. I love going outside, especially ski tours in winter and camping in the summer with my family.
What was your favorite and least favorite course in school? What was the hardest course for you while you were in school?
My favorites depended on the teacher; it could be math, history, biology, or literature, but certainly not Latin. But whatever the teacher, I always liked sports.
We would like to thank Dr. Bruno Antonny for taking time to catch up with us!
Click HERE to learn even more about his exciting research!
* see Manni et al. Acyl chain asymmetry and polyunsaturation of brain phospholipids facilitate membrane vesiculation without leakage. eLife 7, 15114 (2018)