Molecular and cellular mechanisms underlying intestinal regeneration

Supervisor: Dr. Marie-Isabelle Garcia

The gastrointestinal epithelium is one of the tissues with highest self-renewing rates under steady-state conditions, and it thereby constitutes an excellent model to better understand how tissues maintain homeostasis. In the past decade, intense research in this field has allowed identifying resident multipotent stem cells responsible for this task and has contributed to uncover the main molecular mechanisms associated with self-renewal and differentiation properties of these cells in the intestine under homeostasis. Upon injury, multiple types of active or quiescent stem cells showing potential interconversion have been reported, but basic research is still needed to get a full picture of potential relationships between these various cell types and molecular pathways controlling their activated or dormant state in steady-state or regeneration conditions. Besides, our group has recently shown that regeneration can also be promoted through cell de-differentiation in the adult intestine, a mechanism involving partial re-expression of a fetal transcriptomic program.

The proposed PhD project aims to get further understanding on the molecular and cellular mechanisms that are associated with intestinal regeneration in order to design new therapies in patients with gastro-intestinal disorders. It will combine several complementary approaches, including in vivo studies using transgenic mice models as well as the 3D ex vivo culture technology, which offers the possibility to study multi-organs in a petri dish. This program will involve an interdisciplinary knowledge across molecular and cellular biology, transcriptomics, animal handling, tissue processing and immunohistological methods

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