Calcium (Ca2+) signaling and its interplay with cellular mechanics plays a crucial role in development as well as in most other body processes, but it is poorly understood. Recent technical advances in molecular and live imaging provide an unprecedented opportunity to understand the complex mechanochemical processes of development. However, the large imaging datasets generated should now be carefully interpreted.
That's where I come in!
In embryogenesis, malformations and cancer can result when the complex mechanochemical mechanisms go wrong. My role is to investigate the role of Ca2+ signalling in the development of the central nervous system (CNS) in embryos by developing computational models.
During the development of the CNS, cells undergo a dramatic shape change termed Apical Constriction. When Apical Constriction goes amiss, it can result in Spina Bifida - the second most frequent embryo malformation. I aim to elucidate the mechanism of Apical Constriction and, ultimately, inform clinical practice in order to reduce the number of cases with Spina Bifida.
Modelling Calcium Signalling in Embryogenesis
This project investigates an interdiscplinary problem that combines chemical signalling with biomaterials modelling. Modelling biological materials is a formidable, open challenge in Mathematical and Computational biology. The embryonic tissue is a complex biological material and we will explore different types of materials such as viscoelastic materials.
Continuum models: I have been studying mechanochemical models of embryonic epithelial tissue by modelling them as a system of non-linear partial differential equations (PDEs) over a viscoelastic continuum. I use software packages like MATLAB, COMSOL Multiphysics and Wolfram Mathematica to model these equations.
Cell-based models: In this class of models, each cell is modelled individually. I will be using CHASTE (http://www.cs.ox.ac.uk/chaste/) - an open-source, modelling framework aimed at multi-scale, computationally demanding problems arising in biology, to develop the cell-based mechanochemical models.
Data analysis of recent experiments will be undertaken in close collaboration with experimentalists (Skourides lab, University of Cyprus) to inform the development of the computational models (both, cell-based and continuous). On the basis of laboratory data, we will be able to determine how effectively a particular class of models can simulate the different biological phenomena in silico. We will then use the models to explore scenarios that cannot be explored in the lab and inform the design of new experiments.
The work is funded by a Vice Chancellor’s Scholarship for Research Excellence. The results of this project will be used to inform future experiments and, ultimately, clinical practice.