Travelling waves driven by an inflammation-evolution feedback loop in inflammatory bowel disease #

Blaine Van Rensburg, Fabian Spill

14:50 Tuesday in 4Q04.

Abstract #

Our cells, particularly stem cells, divide, mutate, die, and pass on their (epi)genetic information. As such, they are subject to selective pressures according to their local microenvironment. The process of our cells evolving within our body is referred to as “somatic evolution” and it appears that somatic evolution may have a complex relationship with various chronic diseases including inflammatory bowel disease, liver disease, and normal ageing. In all of these cases one observes the emergence of clonal expansions.

The microenvironment is also altered during diseased states and during normal ageing. If the emerging clonal populations of cells themselves impact the microenvironment then this produces a feedback loop. By understanding the role somatic evolution plays in the progression of chronic diseases and ageing it presents new opportunities for interventions.

To this end, we study a reaction-diffusion system which models the feedback between inflammation and somatic evolution in the specific case of inflammatory bowel disease, and analyse the possible travelling wave solutions. We show that this system has a variety of behaviours depending on initial conditions and parameters, and comment on how these behaviours may be related to clinical outcomes like remission and relapse. In our analysis, we also use the “narrow reaction zone” method to determine an asymptotic formula for the wavespeed in a limiting case which relates inflammatory parameters to the rate of disease progression.