© Pau Barnadó

Pau BernadóCentre de biochimie structurale (CBS) - CNRS / Inserm / Université de Montpellier

Structure and function of Intrinsically Disordered Proteins

Mes recherches

My research interests focus on the structural and dynamic characterization of disordered proteins and how these features are connected with their biological function. To achieve these goals I synergistically apply Nuclear Magnetic Resonance, Small-Angle X-ray Scattering and computational approaches. After receiving the PhD at the Universitat de Barcelona I did my postdoc and the IBS-Grenoble and a short visit at the EMBL-Hamburg. Then, I was working as a research assistant at the IRB-Barcelona to finally obtain in 2011 a CR1-INSERM position at the Centre de Biochimie Structurale (CBS) in Montpellier. I joined the CBS with an ATIP-Avenir award in 2012 where I am leading the “structure and function of highly disordered proteins” group since then. In our group we study disordered proteins involved in signalling, regulation and neurodegeneration. Moreover, I develop data analysis chemical biology approaches to bring new biophysical information to study this family of proteins. In 2015 I was awarded with an ERC-CoG to study the protein huntingtin and the the structural bases of Huntington’s disease.

Mon projet ATIP-Avenir

SPIN-HD: Structural insights into protein forms involved in Huntington’s disease by integrative approaches

Huntington’s disease (HD) is a neurodegenerative pathology caused by mutation of the huntingtin gene that results in a protein with an expanded (>35) stretch of glutamines that forms amyloidogenic depositions. In this project I studied the structural study of relevant species of huntingtin involved in HD.

The structural characterization of the N-terminal region huntingtin was performed by combining NMR and SAXS experiments. The structural models of huntingtin derived from the integration of all experimental data unravel the molecular origin of the instability in proteins with expanded glutamine tracts.

The oligomeric species found along the aggregation of huntingtin are hypothesized to be the toxic as shown in other neurodegenerative diseases. The structure and the origin of the toxicity of these species remain elusive due to the polydisperse nature of amyloidogenesis. Chemometrics analysis of SAXS data recorded during fibre formation allowed its decomposition and overcome the polydisperisity problem. The structural details of the species involved in fibrillation and the kinetics of the pathway emerged.

Strategies designed are of general applicability to other polyQ diseases and neuropathologies such as Alzheimer and Parkinson.

Pau Bernadó est également lauréat ERC Consolidator Grant 2015