In-Vitro Fertilization (IVF) is the primary treatment of infertility with over 2.5 million IVF treatments and ~500,000 births per year. The success rate has been ~25% for many decades but has been decreasing. Meanwhile, the IVF industry is projected to grow to 37.7 billion (USD) by 2027 with an ~10% annual growth rate. Success rates are now declining mainly because of culturing embryos for 5-6 days to select the ‘best' single embryo for transfer but this is not ideal because in vitro conditions never full mimic in vivo conditions. Τhis project will pave the way for providing embryologists with a novel diagnostic tool, a rapid (day 1) quantitative indicator of embryo viability. This novel methodology is based on monitoring calcium (Ca2+) signalling in fertilising eggs and the associated egg movements and flows. The methodology was pioneered in a collaboration between the Swann lab (Cardiff Biosciences) and labs in Oxford and Cambridge in 2011 but has not progressed, partly due to the lack of accurate, sophisticated mathematical modelling. A patent (granted to Cambridge Enterprise Ltd and based on the latter experiments) has been recently allowed to lapse because of lack of quantitative progress. This timely PhD project will close this gap through advanced mechanochemical modelling, simulation and data analysis. This ground-breaking diagnostic technology will be eventually deployed to IVF clinics, pushing the frontier in IVF.
Ca2+ waves and oscillations at fertilization are integral in fertilization. There is an optimal Ca2+ pattern associated with successful IVF but monitoring Ca2+ damages the egg. It has, however, been recently observed that Ca2+ waves cause subtle movements (spasms) and flows in eggs and these can be instead detected non-invasively, through low-cost imaging.
To advance the technology the coupling between Ca2+ waves and egg cytoplasmic movements must be elucidated through modelling and more experiments. It is also unclear how to optimize the signal to noise for tracking egg movements that vary over time and from one egg to another.
The student will develop advanced modelling, coding and data analysis skills while working with the Swann lab at the forefront of biological discovery. They will communicate across disciplines, constantly translating ideas between Biology and Mathematics, generating predictions that can be used in further experiments. They will join the Applied and Computational Maths group which includes a vibrant Mathematical and Computational Biology team. The student will be ideally positioned for further work in academia or industry.
This is an ambitious project at the forefront of smart, data-driven healthcare technologies and lies at the Mathematical Sciences/ Life Sciences interface.
The student will develop advanced modelling, simulation and data analysis skills that will contribute to the development of a novel, non-invasive diagnostic IVF technology. The acquired skills will ideally position them to pursue an exciting career in academia or industry. They will be improving IVF by developing and analysing data-driven multiscale models employing Ordinary and Partial Differential Equations. Furthermore, they will be trained in developing stochastic simulations and in implementing cutting-edge imaging methods.
In close collaboration with the Swann lab (Cardiff Biosciences), the student will observe experiments with mouse and human eggs and drive data extraction. The model predictions will inform testable experimental questions, shedding light on factors underlying IVF success. The student will employ statistical methods, including Bayesian Parameter Estimation, to parameterise, validate and test the models.
They will join the vibrant group of Applied and Computational Mathematics which hosts a number of research students working on Mathematical and Computational Biology projects related to fertilization and embryogenesis - supervised, in different combinations, by Kaouri, Woolley, and Phillips and co-supervised by Swann. The supervisory team has an excellent publication record, and regularly presents at international conferences.
The project will generate novel and impactful mathematical results and data that will be published in high-impact journals, aiding the student’s career development. At least three high-impact papers will be generated and the student will present in at least two international conferences.
HOW TO APPLY
Applicants should apply through the Cardiff University online application portal, for a Doctor of Philosophy in Mathematics with an entry point of October 2021
In the research proposal section of your application, please specify the project title and supervisors of this project.
There is no requirement to submit a research proposal
In the funding section, please select "I will be applying for a scholarship / grant" and specify that you are applying for advertised funding from EPRSC Maths DTP.