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dc.contributor.advisorMeere, Martin
dc.contributor.advisorPiiroinen, Petri
dc.contributor.authorDoherty, Kevin
dc.description.abstractThis thesis describes the development and analysis of new mathematical models of Centromere Protein A (CENP-A) incorporation in mammalian centromeres, intermolecular autophosphorylation and Aurora B kinase activity in prophase and metaphase. The models are all developed using a dynamical systems approach. CENP-A is incorporated as part of nucleosomes at centromeres and is required for correct chromosome segregation in mitosis. A first mathematical model of CENP-A incorporation is developed in Chapter 3. The results of simulations of this model are presented in Chapter 4. The model correctly produces the behaviour of the system and helps explain apparently conflicting experimental results. In Chapter 5, a generic model of intermolecular autophosphorylation is developed. The model includes dephosphorylation by a phosphatase of constant concentration, and predicts a threshold concentration for the phosphorylation of enzyme and the possible existence of a bistable switch. Aurora B is a mitotic kinase that localises to centromeres in prophase and metaphase and is vital in ensuring correct attachment of kinetochores to microtubules. A first model of Aurora B binding and activation is developed in Chapter 6 based on the autophosphorylation model of Chapter 5. The model supports the hypothesis that it is possible for soluble Aurora B in the cytoplasm to activate due to binding at centromeres. Both CENP-A and Aurora B play important roles in cellular regulation and have been identified as targets of cancer therapies due to their roles in cell division. The mathematical models developed in this thesis help to shed light on key mechanisms in the functioning of the cell.en_US
dc.subjectSystems biologyen_US
dc.subjectMathematics, Statistics and Applied Mathematicsen_US
dc.subjectMathematics Departmenten_US
dc.subjectCollege of Scienceen_US
dc.titleMathematical models of centromere associating proteinsen_US
dc.contributor.funderCollege of Science, NUIGen_US
dc.local.noteThis thesis describes the development of new mathematical models of important processes in cell biology that are currently attracting much research. Mathematical modelling of the kind in this thesis is useful for interpreting experimental results, shedding light on the underlying dynamics and suggesting future directions for research.en_US

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