9 results found
Sturrock M, Murray PJ, Matzavinos A, et al., 2015, Mean field analysis of a spatial stochastic model of a gene regulatory network, JOURNAL OF MATHEMATICAL BIOLOGY, Vol: 71, Pages: 921-959, ISSN: 0303-6812
Chaplain M, Ptashnyk M, Sturrock M, 2015, Hopf bifurcation in a gene regulatory network model: Molecular movement causes oscillations, International Journal of Mathematical Models and Methods in Applied Sciences, Vol: 25, Pages: 1179-1215, ISSN: 1998-0140
Sturrock M, Dawes AT, 2015, Protein abundance may regulate sensitivity to external cues in polarized cells, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 12, ISSN: 1742-5689
Sturrock M, Hellander A, Aldakheel S, et al., 2014, The Role of Dimerisation and Nuclear Transport in the Hes1 Gene Regulatory Network, BULLETIN OF MATHEMATICAL BIOLOGY, Vol: 76, Pages: 766-798, ISSN: 0092-8240
Sturrock M, Hellander A, Matzavinos A, et al., 2013, Spatial stochastic modelling of the Hes1 gene regulatory network: intrinsic noise can explain heterogeneity in embryonic stem cell differentiation., Journal of the Royal Society Interface, Vol: 10, ISSN: 1742-5689
Individual mouse embryonic stem cells have been found to exhibit highly variable differentiation responses under the same environmental conditions. The noisy cyclic expression of Hes1 and its downstream genes are known to be responsible for this, but the mechanism underlying this variability in expression is not well understood. In this paper, we show that the observed experimental data and diverse differentiation responses can be explained by a spatial stochastic model of the Hes1 gene regulatory network. We also propose experiments to control the precise differentiation response using drug treatment.
Sturrock M, 2013, Spatio-Temporal Modelling of Intracellular Signalling Pathways: Transcription Factors, Negative Feedback Systems and Oscillations, New Challenges for Cancer Systems Biomedicine, Editors: D'Onofrio, Cerrai, Gandolfi, Publisher: Springer Science & Business Media, ISBN: 9788847025714
The aim of this book is not only to illustrate the state of the art of tumor systems biomedicine, but also and mainly to explicitly capture the fact that a increasing number of biomedical scientists is now directly working on mathematical ...
Sturrock M, Terry AJ, Xirodimas DP, et al., 2012, Influence of the Nuclear Membrane, Active Transport, and Cell Shape on the Hes1 and p53-Mdm2 Pathways: Insights from Spatio-temporal Modelling, BULLETIN OF MATHEMATICAL BIOLOGY, Vol: 74, Pages: 1531-1579, ISSN: 0092-8240
Sturrock M, Terry AJ, Xirodimas DP, et al., 2011, Spatio-temporal modelling of the Hes1 and p53-Mdm2 intracellular signalling pathways, JOURNAL OF THEORETICAL BIOLOGY, Vol: 273, Pages: 15-31, ISSN: 0022-5193
Terry AJ, Sturrock M, Dale JK, et al., 2011, A spatio-temporal model of Notch signalling in the zebrafish segmentation clock: conditions for synchronised oscillatory dynamics., PLOS One, Vol: 6, ISSN: 1932-6203
In the vertebrate embryo, tissue blocks called somites are laid down in head-to-tail succession, a process known as somitogenesis. Research into somitogenesis has been both experimental and mathematical. For zebrafish, there is experimental evidence for oscillatory gene expression in cells in the presomitic mesoderm (PSM) as well as evidence that Notch signalling synchronises the oscillations in neighbouring PSM cells. A biological mechanism has previously been proposed to explain these phenomena. Here we have converted this mechanism into a mathematical model of partial differential equations in which the nuclear and cytoplasmic diffusion of protein and mRNA molecules is explicitly considered. By performing simulations, we have found ranges of values for the model parameters (such as diffusion and degradation rates) that yield oscillatory dynamics within PSM cells and that enable Notch signalling to synchronise the oscillations in two touching cells. Our model contains a Hill coefficient that measures the co-operativity between two proteins (Her1, Her7) and three genes (her1, her7, deltaC) which they inhibit. This coefficient appears to be bounded below by the requirement for oscillations in individual cells and bounded above by the requirement for synchronisation. Consistent with experimental data and a previous spatially non-explicit mathematical model, we have found that signalling can increase the average level of Her1 protein. Biological pattern formation would be impossible without a certain robustness to variety in cell shape and size; our results possess such robustness. Our spatially-explicit modelling approach, together with new imaging technologies that can measure intracellular protein diffusion rates, is likely to yield significant new insight into somitogenesis and other biological processes.
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