Mathematical modelling of cell cycle network motifs controlling M-Phase progression

Eukaryotic cells must coordinate growth, replication of their genetic material, and cell division in order to generate two progeny cells from a single progenitor. M-phase is a critical phase of this process during which newly replicated DNA is precisely segregated into two distinct fractions, followed by cell division to produce two new daughter cells. M-phase is a component of both the mitotic cell cycle, during which each daughter cell should inherit an exact copy of the genetic material from the parent cell, and of meiosis, during which each daughter should receive only half of the genetic material from the parent cell to generate a haploid gamete. Despite these differences, both mitotic and meiotic M-phases share many of the same regulatory components. In this thesis we present work from four different studies in which mathematical modelling is used to analyse the behaviour of the biochemical reaction networks controlling M-phase progression in mitosis and meiosis. We firstly present a theoretical analysis of a conserved network motif (termed here the Feedback-amplified Domineering Substrate or FADS motif), which is responsible for creating bistable switches controlling cell cycle progression at multiple points, including progression through and exit from mitotic M-phase. We then present three sets of work using mathematical models in combination with data provided by experimental collaborators to examine the regulation of M-phase progression in mitosis and meiosis. We present evidence for how variations on common regulatory themes can generate the distinct outcomes required in each case.