Exploring the effect of interactions on multicellular spatial structures, stability of gene expression and microbial evolution

Abstract

There are many ways that cells in a colony can interact with one another. For example, metabolic cross-feeding often occurs in bacterial communities where some cells secrete diffusible metabolites that are taken up and utilized by other cells. Such diffusion-mediated forms of communication are also used in certain multi-cellular tissues through the secretion of morphogens that can regulate cellular growth rates. In Chapters 1 and 2 of this dissertation, we explore how the rules governing these interactions can be programmed within cells to achieve desired spatial structures. The implementation of these rules involves cells varying their phenotype based on local environmental conditions, and hence requires gene expression to be regulated. The expression levels of many genes are regulated by proteins known as transcription factors. giving rise to a large system of interacting components. In Chapter 3, we study the stability of such a large gene regulatory network. In Chapter 4, we then explore how the presence of interactions between genes can affect long-term fitness evolution by studying the dynamics on a rugged fitness landscape.