Supervisor: Dr. Isabelle Garcia
Our research focuses on understanding the molecular and cellular mechanisms that regulate the gastrointestinal tract in normal conditions and during diseases such as chronic inflammatory bowel disease and cancer. We pay special attention to G protein-coupled receptors (GPCRs), as they are the main targets of most available drugs (website: https://www.iribhm.org/marie-isabelle-garcia).
Project 2-Regeneration biology-Stem cell biology
Uncovering the role of odorant receptors in colon regeneration
Context:
Did you know that receptors responsible for smell might also play a key role in gut health and regeneration?
Odorant receptors are chemoreceptors located in the membranes of olfactory receptor neurons, responsible for detecting smells. In the olfactory epithelium, activation of these receptors triggers nerve impulses that transmit odor information to the olfactory bulb in the brain. Since their discovery in the 1990s, several olfactory receptors have been found to be ectopically expressed in non-olfactory tissues.
This project aims to investigate the physiological role of one member of this family of odorant GPCRs in the colon. Our group 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 cell differentiation. Loss of Olfr78 expression in the epithelium disrupts colon homeostasis and is associated with dysbiosis, indicating a physiological role for this receptor in gut function. Interestingly, Olfr78 is also detected in colon stromal cells, which contribute to tissue regeneration in adult tissues. The function of Olfr78 in these cells remains unknown.
Project:
The proposed PhD project will explore the role of Olfr78 in adult homeostasis and gut regeneration using conditional knockout transgenic mice and lineage-tracing experiments. This research will integrate molecular and cellular biology, transcriptomics, animal handling, tissue processing, and immunohistology.
Joining our laboratory offers:
– a dynamic international research environment with strong expertise in GPCR and intestinal biology, and cutting-edge technologies.
– collaborative projects within the GHoPaT group (GPCR in Homeostasis & Pathology),
– weekly scientific meetings for PhD students of the GHoPaT group
– personalized mentoring for career development.
Candidate profile:
Highly motivated, independent organizational skills, with strong collaborative abilities
Strong interest in stem cell biology, regeneration, and molecular mechanisms.
Skills in cell culture, molecular biology, or animal handling is a plus.
Excellent English level