Institut de Biologie StructuraleGrenoble / France

ERC Starting Grant 2014 for Hugues Nury

The European Research Council (ERC) has awarded a "Starting Grant" to Hugues Nury for his project of structural studies of mammalian Cys loop receptors.

Hugues Nury is a research fellow at the Institute de Biologie Structurale in Grenoble (CEA / CNRS / UJF mixed research unit). His project entitled "PentaBrain" will receive € 1.5 million financial support from the ERC over 5 years. Scientific excellence at European level is one of the main criteria for the selection of these awards which recognize innovative projects of promising researchers, who earned their doctorate 2 to 7 years ago and want to create or consolidate a research team.

During his PhD at IBS, Hugues Nury studied mitochondrial membrane protein structures. He specialized in bacterial Cys-loop receptors during a first postdoc at the Institut Pasteur (France) in the laboratories of Corringer and Delarue. He then moved on to work on the mouse 5-HT3 serotonin receptor at the EPFL (Switzerland) during a second postdoc in the laboratory of Vogel. Since 2013, Hugues works at IBS and recently deciphered the X-ray structure of serotonin receptor. This collaborative study, published in Nature last year, paves the way for the design of new drugs against nausea, a main side effect of chemotherapy and anesthesia.

What is this project about?
In the brain, Cys-loop receptors mediate fast neurotransmission. They function as allosteric signal transducers across the plasma membrane: upon binding of one or more neurotransmitter molecules to an extracellular site, the receptors undergo complex conformational transitions that result in transient opening of an intrinsic ion channel. The Cys-loop family comprises receptors activated by serotonin, acetylcholine, glycine and GABA. Mammalian receptors are also the targets of a legion of psycho-active and therapeutic compounds (including nicotine, benzodiazepines, anti-emetics, general anaesthetics). Our structural knowledge is currently limited to invertebrate homologues. Atomic structures mammalian receptors are therefore acutely missing in order to understand their physiological role in molecular terms, and to be able to develop new drugs targeting them.
The project proposes to decipher the operation mechanism, the pharmacology and conformational transitions of mammalian Cys-loop receptors. Starting with a solid body of preliminary results, the researchers will try and obtain new high-resolution structures (currently our knowledge is limited to only two family members in mammals), taking advantage of antibody-based crystallization chaperones. They will try to record for the first time a ‘molecular movie’ of the gating conformational transition in cristallo. On the way, they will also investigate the potential of antibody-based modulators of Cys-loop receptors for biomedical applications.

Keywords: neurotransmission, ionic channels, serotonine receptor

Amount of the award : €1.5 million for five years

Mini CV :
34y, 1 child
PhD at IBS in 2007
Researcher in Membrane Tansporters Group at IBS since 2013
Publications : consult google scholar profile