Mathematical models of centromere associating proteins
MetadataShow full item record
This item's downloads: 414 (view details)
This 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.
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. Please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.
The following license files are associated with this item:
Showing items related by title, author, creator and subject.
Burns, Shane Joseph (2015-11-19)This thesis gives a flavour of the area of rigid body impacts with friction, an area which has far reaching applications in engineering, sports science and every day life. The focus of this work will be on the two main ...
Mangan, Robert (NUI Galway, 2018-07-10)This article-based thesis comprises a collection of four articles, each of which constitutes a chapter written and formatted in pre-print manuscript form. The general aim underlying these articles is to model the large ...
Makrooni, Mohammad Adib (2016-06-20)Using the algebraic structure of subroot systems in the root system of a complex simple Lie algebra g, we prove a generalization for compact homogeneous spaces with positive Euler characteristic of the 'strange formula' ...