A Network of Lipid-Transfer Proteins at the Crossroads between Metabolism and Signalling

BIOENGINEERING SEMINAR
 
Abstract:
Lipid metabolism attracts much attention owing to the pleiotropic roles of lipids and their roles in human pathologies. This interest motivates growing efforts dedicated to cataloguing the lipidome. All aspects of lipid function rely on their heterogeneous distribution in living systems and the formation of molecular signatures that define organelle membranes or microdomains. Lipid metabolism – and its associated disorders – needs to be understood in the context of this functional, three-dimensional organization.

We developed systematic approaches for lipid biology, integrating proteomics, lipidomics, microfluidics and bioinformatics. Understanding how cell signaling – and many biological functions – can be modulated by discrete changes in the chemical properties of cellular membranes and how this affects the switching behavior of specific signaling lipids represents our first research interest. Many lipids have signaling functions and form molecular signatures that are read by specialized lipid-binding domains on effector – the so-called (and still elusive) “lipid code”. We discovered that discrete changes in specific lipid concentrations or in the collective properties of all lipids in different membranes affect the functioning and efficiency of downstream signaling. This has broad implications for human health, as 60% of all drug targets reside in biological membranes. Another research interest concerns the study of the mechanisms involved in the creation and maintenance of lipid gradients in eukaryotic cells. An emerging player in these processes is a group of disease-associated proteins known as lipid-transfer proteins (LTPs). They spatially organize lipids and connect lipid metabolic pathways that are distributed across distinct organelles, but our knowledge of these transport mechanisms remains fragmented. I will present a number of new large-scale biochemical methods designed to systematically characterize the pathways of LTP-mediated lipid movement.

Bio:
Anne-Claude Gavin grew up in Switzerland and received her M.Sc. and Ph.D. from the Faculty of Science of the University of Geneva. After her doctorate in 1992, she did a post-doctoral internship at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. Her research interest concerned the study of the signaling events that regulate of the progression of the cell cycle. She then joined a start-up company, Cellzome in Heidelberg, as a founding Scientist and Director of the Molecular and Cellular Biology Department. After 5 years, she started her own research group at EMBL, first as group leader and then a senior scientist. During these periods, she established a research programme that aims at the development of systems biology approaches (integrating proteomics, lipidomics, microfluidics and bioinformatics) and the characterization of cellular networks important for human pathologies, with strong research focus on lipid metabolism and biological membrane homeostasis. This work has received wide recognition in the field, including highly cited papers and many follow up studies. In 2014, she was appointed a member of EMBO. Her work on lipid metabolism, lipid transport mechanisms and their disfunctions in certain human pathologies led her to be appointed Full Professor, Chair Louis Jeantet, in 2019, et the University of Geneva. Since 2019, Anne-Claude Gavin has been a partner of the NCCR module, "Chemical Biology". Anne-Claude has given multiple invited talks at international conference, co-organized several international conferences, co-authored more than 80 peer-reviewed papers - among them 11 were published in Nature, Cell and Science - accumulating more than 10’000 citations. She frequently serves as journal reviewer and is an editorial board member of  Molecular & Cellular Proteomics.