Speaker
Description
The epithelium is the tissue that separates us from the outside. Healthy epithelia are simultaneously plastic and robust, dynamically responding to changing environments without large or long-lasting deviations from a homeostatic set point. This fine balance is achieved through an exquisitely connected network of regulatory interactions between epithelial barrier function, immune response, and microbiome. How is epithelial homeostasis maintained? How lost, resulting in inflammation, mucosal infections or carcinomas? To answer these questions, I propose a minimal mathematical model of epithelial function to characterise the phenotypic plasticity that can result from alterations to this network, and map regions in the phenotypic space corresponding to the diversity of health and disease manifestations. Through bifurcation analysis I identify the inherent vulnerabilities of this network leading to deviations from homeostasis and suggest possible pathophysiological trajectories connecting clinical manifestations. This model unveils general principles governing epithelial homeostasis. It is a useful tool to systematically explore the effect of genetic and environmental alterations on homeostasis; identify the mechanisms underlying abrupt pathophysiological transitions; characterise the early warning signals preceding these catastrophic shifts; and design and optimise therapeutic interventions for disease prevention and reversal, even when extensive empirical data is limited.
