PhD Odorant receptors (M/F): G PROTEIN-COUPLED ODORANT RECEPTOR FUNCTION

ICSN - CNRS - UNIVERSITÉ PARIS SACLAY
Gathering a 200-collaborator staff, the ICSN is the chemistry center of the CNRS campus in Gif sur Yvette. The Institute belongs to the Paris-Saclay University Campus, which incorporates 10% of the French research. The ICSN develops research activities at the boundary between chemistry and biology, that draw inspiration from natural substances. ICSN is organised into four research departments and has important analytical platforms

n order to navigate our volatile environment, we constantly rely on our sense of smell. In mammals, it is now well established that olfactory receptors play an important role in olfaction and other crucial developmental and physiological processes, some of which are associated with serious health issues. The exact molecular mechanism by which olfactory receptors accomplish their function is not fully understood and requires atomic-scale information, which has been largely lacking. This is a relatively understudied family of proteins, even though it represents nearly half of the large family of G protein-coupled receptors, primarily because, until recently, there were no experimental structures of mammalian olfactory receptors. The lack of expression of olfactory receptors in eukaryotic cell models used for expressing recombinant membrane proteins is the main obstacle in addressing this challenge. We have succeeded in unlocking their expression in a cell model through the construction of "consensus" receptors that summarize all the properties of human olfactory receptors, allowing us to publish the first structure of an olfactory receptor this year. The project will focus on studying the expression of innovative olfactory receptor constructs on the surface of HEK cells using flow cytometry, as well as measuring their response to odorant molecules of interest for perfumery and drug design. The visualization and characterization of the structures of these receptors and their binding with odorant molecules will be conducted through molecular modeling. This thesis will therefore involve methods of biochemistry, cell culture, and molecular modeling.
Minimum publication during the PhD: one review article, one protocol, and two research articles. Possibility of collaboration with the Monell Center, Duke University, University of California San Francisco, and City of Hope (USA).