Mathematical modelling -- Cancer -- Chaste
Colorectal cancer (CRC) is thought to originate via genetic alterations that cause disruption to the dynamics of the crypts of Lieberkuhn, test-tube shaped glands that line the small and large intestine. It is believed that during carcinogenesis,cells accumulate genetic mutations that destabilise cell-cell contacts and disturb division and migration. The resulting abnormal behaviour can increase stress on the walls of the crypt, causing buckling. Such dysplastic crypts can allow the formation of a benign adenoma if mutated cells do not leave the crypt as they should, but rather persist and proliferate in a localised area. Over time and via accumulated mutations, such a growth can progress to a malignant lesion that can break through to the underlying tissue stroma, and so aid metastasis. To provide insight into the tissue-level effects of the initial genetic mutations, a multi-scale model of the crypt with a realistic, deformable geometry is required. My research concerns the development of such a model, and its usefulness as a predictive tool to further the understanding of interactions across spatial scales in the context of CRC.
Ten simple rules for effective computational research
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Chaste: an open source C++ library for computational physiology and biology
G.R. Mirams‚ C.J. Arthurs‚ M.O. Bernabeu‚ R. Bordas‚ J. Cooper‚ A. Corrias‚ Y. Davit‚ S−J. Dunn‚ A.G. Fletcher‚ D.G. Harvey‚ M.E. Marsh‚ J. M. Osborne‚ P. Pathmanathan‚ J. Pitt−Francis‚ J. Southern‚ N. Zemzemi and D.J. Gavaghan
In PLoS Computational Biology. Vol. 9. No. 3. Pages e1002970. 2013.
A two−dimensional model of the colonic crypt accounting for the role of the basement membrane and pericryptal fibroblast sheath
S.−J. Dunn‚ P.L. Appleton‚ S.A. Nelson‚ I.S. Näthke‚ D.J. Gavaghan and J.M. Osborne
In Plos Computational Biology. No. 5. Pages e1002515. 2012.