About the Project
Background
Calcium (Ca2+) signalling 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 now generated should be carefully interpreted. In embryogenesis, congenital malformations and cancer can result when the mechanochemical, complex mechanisms go wrong. In the development of the central nervous system, cells undergo a dramatic shape change, called Apical Constriction (AC), which generates a mechanical force and triggers the neural plate to form a tubular structure in Neural Tube Closure (NTC). When NTC fails the second most frequent embryo malformation occurs; Spina bifida. Despite its importance, AC is only partially understood.
It has recently been established in experiments that contractions play a crucial role in AC, that they are calcium-driven and that disrupting the Ca2+ signals leads to malformations. Very few models of Ca2+ signalling in AC exist and even fewer mechanochemical models. Dr Kaouri in collaboration with leading mathematical modellers in Oxford and experimentalists in Cambridge and Cyprus, has recently developed a simple mechanochemical model, consisting of coupled nonlinear ordinary differential equations, in which embryonic tissue is modelled as a continuum viscoelastic medium (Kaouri et al, J. of Math. Biology, 2019, DOI: 10.1007/s00285-019-01333-8) This work provides a framework for understanding the mechanochemical coupling in AC.
In this project the student will extend this model to systems of nonlinear partial differential equations to model the rheology of the embryonic epithelial tissue. Furthermore, cell-based mechanochemical models will be developed using Chaste (http://www.cs.ox.ac.uk/chaste/) a comprehensive, open-source, cell-based modelling framework. The cell-based and the continuum mechanochemical models will be compared. The models will be validated with experimental data and then used as predictive tools for exploring scenarios that cannot be explored in the laboratory and thus inform the design of future, feasible, experiments. Our aim is to elucidate the mechanism of Apical Constriction, understand Spina Bifida and ultimately inform clinical practice.
The project will be co-supervised by
Professor Philip Maini, Wolfson Centre for Mathematical Biology
Professor Ruth Baker, Mathematical Institute, University of Oxford
HOW TO APPLY
Applicants should submit an application for postgraduate study via the online application service for Jan/Apr 2020:
http://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/mathematics
In the research proposal section of your application, please specify the project title and supervisors of this project. In the funding section, please select "I will be applying for a scholarship / grant" and specify that you are applying for advertised funding from EPSRC DTP.
If are applying for more than one Cardiff University project please note this in the research proposal section.
Funding Notes
UK Research Council eligibility conditions apply.
Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students who can satisfy UK residency requirements ONLY.
To be eligible for the full award, EU Nationals must have been in the UK for at least 3 years prior to the start of the course for which they are seeking funding, including for the purposes of full-time education.
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