Calcium signalling in in-vitro fertilization
This research project is in competition for funding with one or more projects available across the EPSRC Doctoral Training Partnership (DTP). Usually the projects which receive the best applicants will be awarded the funding. Find out more information about the DTP and how to apply.
Application deadline: 15 March 2019
Start date: 1 October 2019
The aim of this project is to capture the complex interplay of Ca2+ signalling and the cytoplasmic spasms in eggs and make advances that could inform future experiments and ultimately clinical practice.
Calcium (Ca2+) is a life and death signal, the most important second messenger in the body, carrying important information across all our cells. It also plays an essential role in embryo development, beginning at fertilisation when fast Ca+ waves sweep through the egg after sperm fusion and later in embryogenesis, during tissue contractions and movements. These fast waves, or Ca2+ transients, are crucial for the embryo development and the number and pattern of Ca2+ increases is a predictor of the viability of the embryo. Critically, recent experimental evidence has accumulated showing that each Ca2+ increase in the egg causes mechanical effects which can be detected as slight ‘spasms’ in the egg cytoplasm. These cytoplasmic spasms are of particular interest because they could be used to predict which embryo is most likely to go on to give a viable pregnancy. However, surprisingly, very few mathematical modelling efforts have been made in this area. In this project we will analyse experimental data and develop sophisticated mechanochemical mathematical models.
The project has great potential to advance the field of IVF (In-Vitro-Fertilization) with new diagnostic tools. A patent has been granted (to Cambridge Enterprise Ltd) based on experiments in which the Swann lab was involved, but its future is uncertain because of lack of quantitative progress in the field. Therefore, the project is timely and cutting edge as it will provide the mathematical tools to enable the technology to progress. Furthermore, the spatiotemporal dynamics of Ca2+ and cell contractility play a key role in the cutting-edge areas of wound healing and cancer invasion and the results could also be applied in these fields.
Project aims and methods
You will develop multiple theoretical skills, such as: analysis of coupled systems of Ordinary and Partial Differential Equations (ODEs; PDEs) using computational methods, perturbation methods, multiscale modelling, bifurcation theory, direct stochastic simulations, imaging methods, analysis of experimental data.
Dr Katerina Kaouri has recently started collaborating with Prof. Swann and discussing his data sets on the interplay of calcium signalling and mechanics in fertilisation. Recent experimental data from the Swann lab will be analysed and you will learn image processing skills to derive pertinent statistics from the data, with which they will validate the modelling framework. Due to the collaborative nature of the project you will learn to communicate across disciplines, constantly translating ideas between biological and mathematical languages, resulting in useful predictions and explanations for experimentalists and the design of future experiments.