Mechanotransduction in the intestinal epithelium - a role for RhoA in mediating innate immune system - microbiome interactions (360G-Wellcome-203757_Z_16_A)

To have a ‘gut feeling’ is more than an idiom, as the intestine not only digests food and excretes waste, but helps the micro-organisms in our gut interact with the white immune cells in our blood. I will study how these three units interact in real life by creating a replica ‘intestinal immune-system in a dish’, which consists of 3D mini-guts called organoids (1) that I will inject with disease-associated microbiome strains (2) and surround with innate immune lymphoid cells (3), which protect us from infection and help keep the intestinal epithelium healthy. I am interested in improving the culture conditions necessary for the maintenance of this system, using novel hydrogels and bioengineering techniques to make it as similar to the human body as possible. I will then use this model to study why the composition of the microbiome has such a dramatic impact on human health and well-being. More specifically, I will use it to understand how environmental and genetic causes act together to cause inflammatory bowel disease, creating a platform to look for new drug targets for the treatment of this severe and incurable disease.