About his PhD Project

Intestinal crypts play an important role in intestinal tissue homeostasis due to their role as a niche for intestinal stem cells, which are needed for renewal of the intestinal epithelium. During late embryonic and postnatal development, intestinal crypts undergo a process called crypt fission (where one crypt divides into two) to give rise to several new crypts [1]. This process also occurs in adults at a lower frequency for intestinal repair [2]. Despite its importance, the process in itself is not very well studied. For my PhD, I will elucidate the exact morphogenetic events that occur during this process by carrying out high-resolution long-term live imaging of mouse intestinal organoids. I will then explore the mechanical landscape (such as the forces and tensions) of the intestinal epithelium during the different stages of crypt fission, using tools such as laser ablation. Regulation of crypt fission by intrinsic factors (such as cytoskeletal proteins) as well as the extracellular matrix will be investigated with fluorescent microscopy to give us a complete picture of the process. This would be crucial for understanding how abnormal crypt fission is implicate in diseases such as colorectal adenomas [3].

Huang XT, Li T, Li T, Xing S, Tian JZ, Ding YF, et al. Embryogenic stem cell-derived intestinal crypt fission directs de novo crypt genesis. Cell Rep. déc 2022;41(11):111796.
Cummins AG, Catto‐Smith AG, Cameron DJ, Couper RT, Davidson GP, Day AS, et al. Crypt Fission Peaks Early During Infancy and Crypt Hyperplasia Broadly Peaks During Infancy and Childhood in the Small Intestine of Humans. J Pediatr Gastroenterol Nutr. août 2008;47(2):153‑7.
Boman BM, Fields JZ. An APC:WNT Counter-Current-Like Mechanism Regulates Cell Division Along the Human Colonic Crypt Axis: A Mechanism That Explains How APC Mutations Induce Proliferative Abnormalities That Drive Colon Cancer Development. Front Oncol [Internet]. 2013;3.