Structure and function of VIP receptors in physiological and pathological conditions
Our research topics focus on the study of GPCRs and particularly the Vasoactive Intestinal Peptide (VIP) receptors. VPAC1, VPAC2 and PAC1, three members of the family B of GPCRs, are widely distributed throughout the body and play important role in human physiology such as in development, growth, immune responses, circadian rhythms, neuronal and endocrine control, neuroprotective actions, and in the functions of the digestive, respiratory, reproductive, and cardiovascular systems.
Our previous works focuses on study structure, function and molecular mechanisms involved in ligand binding and activation of receptors for the VIP family of peptides using multi-disciplinary approaches combining mutagenesis, pharmacology, molecular biology, biochemistry, protein production and engineering. Our studies led to the identification of residues involved in ligand high affinity binding, receptor activation, G protein coupling as well as receptor phosphorylation and downregulation.
Thanks to a collaboration with Jan Steyaert from the Structural Biology Laboratory of the VUB, we generated, by combining genetic immunisation, phage display and biopanning, recombinant single chain monoclonal antibodies from Camelid (Nanobodies) targeting several human GPCRs studied in the laboratory. Characterisation of these nanobodies revealed that they were new innovative and versatile tools to further investigate the role of these receptors in physiological and pathological conditions.
Our current projects are mainly focused on investigating the intricate molecular mechanisms underlying the multiple roles of the VIP/PACAP pathway in disease states of the colonic mucosa using adult stem cell (ASC)-derived organoids as disease models with a main emphasis on epithelial and mesenchymal cells.
Together with Dimitri Gillis (3BIO-Bioinfo, ULB), we are also working on a project that aims to develop artificial intelligence approaches to design molecules capable of activating a given olfactory receptor, as well as a pipeline for experimental analysis of ligand-odor receptor interactions.
Overall, we aim to understand how some GPCRs work at the molecular level with the ultimate goal of potentially developing new diagnostics and therapeutics.