5 mars 2020: Dr Emmanuel Levy
CMU - Auditoire Alex-F. Müller (A250)
DR. EMMANUEL LEVY
Department of Structural Biology
Weizmann Institute of Science, Israel
«Principles of Protein Assembly in Cells»
Life processes involve an intricate choreography between tens of millions of protein building blocks that form the infrastructure of cells. Recent technological advances have revealed the catalogs of proteins present in various cells and organisms. However, understanding how these protein building-blocks assemble and work together is an extraordinarily complex task. I will present recent and unpublished work on principles of protein assembly in cells. First, I will describe how stickiness, defined as the chemical propensity of protein surfaces to bind to each other, is tuned in the yeast and human proteomes to minimize promiscuous interactions. Second, I will expose how protein homo-oligomerization can drive high-order self-assembly and phase-separation. Last, I will discuss how even single mutations changing the surface stickiness of homo-oligomeric proteins can trigger their infinite folded-state self-assembly. Importantly, this assembly mechanism differs fundamentally from aggregation because misfolding does not drive it. To highlight this difference, I term this mechanism agglomeration. Agglomeration causes the sickle cell disease, certain forms of cataract, and our work suggests that many more disorders originate in this mechanism.
Emmanuel Levy is a biologist integrating computational and experimental work to solve nature’s riddles. His research concentrates on the principles of protein assembly. His notable contributions include the determination of physiologically-relevant assembly states for proteins of known structure, the discovery of protein surface hot-spots, where mutations readily trigger new assemblages, and the characterization of negative design principles safeguarding proteins against mis-assembly. Levy did his undergraduate studies in France. He received his Ph.D. in 2008 from Cambridge University, UK, working at the MRC Laboratory of Molecular Biology with Dr. Sarah Teichmann. For his post-doctoral research, he joined the group of Prof. Stephen Michnick at the University of Montreal, Canada. Since 2012, he has been an assistant professor in the Department of Structural Biology at the Weizmann Institute, Israel. Levy was awarded the Blavatnick Award in Chemistry (2020), the Wolf Foundation’s Krill Prize for Excellence in Scientific Research (2018), the HFSP Career Development Award (2015), and the Marie Curie Career Integration Award (2012).
Frontiers in biomedicine