Project description
Cells respond to their physical environment through mechanotransduction, the translation of mechanical forces into biochemical signals; evoked cell phenotypic changes can lead to an altered cell microenvironment, creating a developmental feedback. Interplay between such mechanosentive pathways and other inter- and intra-cellular signalling mechanisms determines cell differentiation and, ultimately, tissue development. Such developmental mechanisms have key relevance to the initiation and development of cancer, a disease of such inherent complexity (involving the interaction of a variety of processes across disparate spatio-temporal scales, from intracellular signalling cascades to tissue-level mechanics) that, despite a wealth of theoretical and experimental studies, it remains a leading cause of mortality and morbidity: in the UK, more than one in three people will develop some form of cancer. There is therefore an urgent need to gain greater quantitative understanding of these highly complex systems, which are well-suited to mathematical study.
This project will develop a predictive framework, coupling key signalling pathways to cell- and tissue-level mechanics, to elucidate key developmental mechanisms and their interaction. Investigations will include both multiscale computational approaches, and asymptotic methods for model reduction and analysis. Importantly, model development, analysis and experimental validation will be enabled via close collaboration with Dr Robert Jenkins (Francis Crick Institute, a multidisciplinary biomedical discovery institute dedicated to understanding the scientific mechanisms of living things), thereby ensuring the relevance of the investigations undertaken.
Experience of mathematical/numerical techniques for ODEs and PDEs, the study of nonlinear dynamical systems, or mathematical biology more generally would be an advantage; prior knowledge of the relevant biology is not required