Supervisor: Dr. Isabelle Garcia
G protein-coupled receptors (GPCR) represent the largest family among membrane receptors. They play a major role in a variety of physiological and pathophysiological processes and constitute the targets for 30% of the active compounds presently used as therapeutic agents. Our objective is to study new paradigms in activation, signalling and regulation of GPCRs and determine their contribution in pathophysiological processes using mice models.
The experimental approach involves cell and molecular biology, pharmacology, organoid culture technology and in vivo studies.
Uncovering the role of ectopic odorant GPCR receptors in colon regeneration
Odorant receptors are chemoreceptors expressed in the cell membranes of olfactory receptor neurons responsible for the sense of smell. In the olfactory epithelium, activated olfactory receptors trigger nerve impulses to relay odor information to the olfactory bulb in the brain (1). Since their discovery in the olfactory epithelium in the 90s, several olfactory receptors have been reported to be ectopically expressed. The current proposal aims to investigate the physiological role of one member of this family of odorant GPCR receptors in the colon (1). Our group has recently discovered that the olfactory receptor Olfr78, which recognizes short chain fatty acids as natural ligands, is expressed in epithelial enteroendocrine cells in the mouse colon where it promotes enterochromaffin differentiation (2). Loss of epithelial Olfr78 expression results in alteration of colon homeostasis and is associated with dysbiosis, indicating a physiological role of this olfactory receptor in the gut (2). Interestingly, Olfr78 is also detected in colon stromal cells that are identified as contributing to tissue regeneration in adult tissues (3). The potential function of the Olfr78 receptor in these cells remains uncovered.
The proposed PhD project aims to determine the potential role of this receptor in adult homeostasis and in regeneration in the gut using conditional knockout transgenic mice and lineage tracing experiments. This program will involve an interdisciplinary knowledge across molecular and cellular biology, transcriptomics, animal handling, tissue processing and immunohistology methods.
Supervisor: M.I. Garcia, PhD
References
- Human Olfactory Receptors Expression and Their Role in Non-Olfactory Tissues.– A Mini-Review Abaffy, J Pharmacogenomics Pharmacoproteomics 2015, 6:4.
- The olfactory receptor olfr78 promotes differentiation of enterochromaffin cells in the mouse colon. Dinsart et al. EMBO Rep. 2024, 25:304-333.
Colonic healing requires Wnt produced by epithelium as well as Tagln+ and Acta2+ stromal cells. Das et al. Development 2022. Jan 1;149(1):dev199587.