Biophysics and aggregation pathways of amyloids
Our research focuses on the molecular mechanisms underlying neurodegenerative diseases. We have a specific interest for the tau protein, an intrinsically disordered protein present in the brain where it regulates the microtubule activity. Tau is directly implicated in several neurodegenerative diseases, including Alzheimer's disease. In these diseases, called tauopathies, tau aggregates into so-called amyloid filaments, which are deleterious for the survival of neurons and can spread throughout the brain following a prion-like mechanism. Our group studies the formation of these aggregates, the factors that determine their structure, their pathological activity as well as their spreading capacity.
Yann Fichou got an engineering degree in physics and material sciences from the Institut National des Sciences Appliquées (INSA) in Rennes in 2011. He received in 2015 his PhD from the Université Grenoble Alpes where he studied protein and hydration dynamics by neutron scattering and MD simulations, under the supervision of Martin Weik at the Institut de Biologie Structurale (IBS). He carried out a first postdoc in the lab of Martina Havenith at Ruhr-Universität Bochum (RUB, Germany) where he studied protein hydration by THz spectroscopy. From 2016 to 2020, Dr. Fichou carried out a second postdoc at the University of California Santa Barbara (UCSB) in the group of Songi Han. He focused his work on studying the mechanisms of tau aggregation by electron paramagnetic resonance spectroscopy (EPR). Since 2020, Yann Fichou is a CNRS Chargé de Recherche at the institute de Chimie et Biologie des Membranes et Nano-objets (CBMN) in Bordeaux and he became group leader at the Institut Européen de Chimie et Biologie (IECB) after obtaining a ERC starting grant in 2021.
Our research aims at understanding the molecular rules governing aggregate structural differentiation and propagation. Using biophysical and biochemical techniques, we study the mechanisms of tau aggregation across different pathways. We have a particular interest in characterizing the interaction of tau protein with different cofactors such as GAG, nucleic acids and lipids. We also study liquid-liquid phase separation (LLPS) as a potential intermediate toward tau amyloids. Our goal is to understand the driving forces of tau LLPS and its relationship to tau pathological activity, by characterizing the physico-chemical properties of the protein under LLPS. We adopt a multi-technique approach in which we use a large array of biochemical and biophysical methods to characterize protein structure, dynamics, thermodynamics and pathogenicity. We have a particular expertise and interest in electron paramagnetic resonance spectroscopy (EPR) applied to protein sciences.
Alfano Caterina, Fichou Yann, Huber Klaus, Weiss Matthias, Spruijt Evan, Ebbinghaus Simon, de Luca Giuseppe, Morando Maria Agnese, Vetri Valeria, Temussi Piero Andrea, Pastore Annalisa
Pounot Kevin, Piersson Clara, Goring Andrew, Rosu Frédéric, Gabelica Valérie, Weik Martin, Han Songi, Fichou Yann
Talaga David, Cooney Gary, Ury-Thiery Vicky, Fichou Yann, Huang Yuhan, Lecomte Sophie, Bonhommeau Sébastien