Guillaume Lebon,
Group Leader, CR1, CNRS
Institut de Génomique Fonctionnelle,
Neuroscience Department,
“Structural studies of GPCRs”
My research career started as a PhD student with the characterisation of an RNA polymerase subunit for the conception of transcription inhibitor, in Nantes University, with Professor Vehary Sakanyan (2003-2006). In December 2006, I joined the Lab of Dr Ed Hulme, NIMR London (MRC-NIMR), England, in collaboration with GSK, to elucidate the binding and activation mechanism of new muscarinic M1 agonists by using site-directed mutagenesis and molecular modelling. During this fruitful collaboration, we identified the binding site for the new ectopic agonists of muscarinic M1 receptor and described their ligand binding mode. This was for me the starting point of a fascinating research adventure to understand the ligand binding mode and activation mechanism of G protein-coupled receptor, the largest family of integral membrane proteins. In December 2007, I moved to the Laboratory of Molecular Biology (MRC-LMB), Cambridge, to join Dr Chris Tate. During 4 exciting years at the LMB (2007-2011) and in collaboration with Heptares therapeutics, I studied 3D structure of the agonist-bound conformation of the human A2A receptor and I solved the 3D structures of the receptor bound to its natural agonist adenosine and to synthetic agonist NECA using X-ray crystallography. In September 2011 I joined the lab of Dr Jean Philippe Pin in Montpellier. In 2012, I was awarded by the ATIP AVENIR grant and I pursue my effort to decipher at the molecular level how GPCRs internalise an extracellular stimulus and activate intracellular signalling partners such as the trimeric G proteins.
