Stem cell/niche biomechanics in intestinal health and disease
Supervisors:
PhD project summary:
The vasculature is a prominent constituent of multiple stem cell microenvironments and a major target of regenerative and anti-tumour therapy. However, its role in the intestinal stem cell microenvironment remains largely understudied. Recapitulation of the vasculature in 3D cultured organoids has been notoriously challenging, representing a significant hurdle to tissue engineering. Using the adult fruit fly Drosophila melanogaster intestine and its vasculature-like trachea, we have shown that signaling between the intestine and is vasculature is essential for intestinal repair after damage or inflammation. Our new preliminary data suggest mechanosensory signals as major drivers of stem cell/vasculature interactions during intestinal regeneration. Using the fruit fly as an in vivo model for intestinal biology research in this project we will:
1- Use Atomic force and Brillouin microscopy to measure local and global changes in mechanical properties of the intestine and its microenvironment.
2- Build mathematical models to predict cellular perturbation necessary to recapitulate stem cell/vascular dynamics.
3- Use genetic experiments to experimentally test the predictions of our modelling work. The research in this project will identify mechanisms that could be applied in the design of approaches to modify the intestinal vasculature for regenerative medicine and cancer treatment.