Calcium signalling in In-Vitro Fertilization: developing a non-invasive diagnostic tool


   Cardiff School of Mathematics

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  Dr K Kaouri  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

IVF is the primary treatment of infertility with ~2.5 million treatments and ~500,000 births annually. The success rate has been ~25% for many decades but it has been decreasing while the IVF industry is projected to grow to 37.7 billion (USD) by 2027 with an ~10% annual growth rate. Success rates have been declining mainly because of culturing embryos for 5-6 days before selecting the ‘best' single embryo for transfer to the patient. This is not ideal because in vitro conditions never full mimic in vivo conditions. Moreover, the embryos take more of the clinic’s resources and the process is more psychologically taxing for the patient.

Τhis project will pave the way for providing the IVF clinics 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 through 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 has been recently allowed to lapse because of lack of quantitative progress.

This timely PhD project will close the translation and innovation gap through advanced mathematical modelling, simulation and data analysis. Ca2+ waves and oscillations 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; these could be detected non-invasively, through low-cost imaging, such as Particle Image Velocimetry. The coupling between Ca2+ waves and egg cytoplasmic movements will be elucidated in this project through mathematical modelling. It is also unclear how to optimize the signal to noise for tracking egg movements as these vary over time and from one egg to another; the project will also tackle this challenge. 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 should have a strong quantitative background (a degree in Mathematics, Physics, Engineering, Computer Science). They will develop advanced mathematical modelling, coding and data analysis skills while benefiting from the collaboration with the Swann lab which is at the forefront of the IVF field. The student will also observe experiments on fertilizing eggs and guide data extraction. The student will employ sophisticated statistical methods to parametrise, validate and test the models.  The student will, thus, communicate across Mathematics, Biology and Medicine generating predictions that can be used in further experiments. High- impact papers will be generated from the thesis and the student will present in international conferences. At the end of the project the student will be able to pursue an exciting career in academia or in industry.        The student will be based at Cardiff Mathematics and will join the vibrant community of Mathematical and Computational Biology and Medicine across the three participating GW4 universities (Cardiff, Exeter, Bristol). Infertility challenges all countries and the work will have world-wide impact on a large community of scientists and patients. (For some references related to the project see the end of this advert.)

Additional Supervisors – Prof Karl Swann (Cardiff Biosciences, [Email Address Removed]), Prof Krasimira Tsaneva-Atanasova (Exeter, Living Systems Institute, [Email Address Removed]), Dr Cameron Hall (Bristol, Department of Engineering Mathematics, [Email Address Removed]), Dr Thomas Woolley (Cardiff Mathematics, [Email Address Removed])

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase., along with 20 students in its second phase. 

Eligibility

Residency: The GW4 BioMed2 MRC DTP studentships are available to UK and International applicants. Following Brexit, the UKRI now classifies EU students as international unless they have rights under the EU Settlement Scheme. The GW4 partners have all agreed to cover the difference in costs between home and international tuition fees. This means that international candidates will not be expected to cover this cost and will be fully funded but need to be aware that they will be required to cover the cost of their student visa, healthcare surcharge and other costs of moving to the UK to do a PhD. All studentships will be competitively awarded and there is a limit to the number of International students that we can accept into our programme (up to 30% cap across our partners per annum).

Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a UK degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences, computing, mathematics or the physical sciences. Please check the entry requirements of the home institution for each project of interest before completing an application. Academic qualifications are considered alongside significant relevant non-academic experience.

English requirements: If English is not your first language you will need to meet the English language requirements of the university that will host your PhD by the start of the programme. Please refer to the relevant university for further information.

How to Apply

A list of all the projects and how to apply is available on our website at gw4biomed.ac.uk. You may apply for up to 2 projects.

Please complete an application to the GW4 BioMed2 MRC DTP for an ‘offer of funding’. You may also need to make an application for an 'offer to study' to your chosen institution(s) – further details are on the website.

Please complete the online application form by 5.00pm on Wednesday, 2nd November 2022. If you are shortlisted for interview, you will be notified by Friday 16th December 2022. Interviews will be held virtually on 25th and 26th January 2023.

Biological Sciences (4) Mathematics (25)

Funding Notes

The GW4 BioMed2 MRC DTP is offering up to 20 funded studentships across a range of biomedical disciplines, starting October 2023
The four-year studentship provides funding for fees and stipend, as well as other research training and support costs, and are available to UK, EU, and International students.
Funding consists of UK tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£16,062 p.a. for 2022/23, updated each year). Additional research training and support funding of up to £5,000 per annum is also available.
Part time study is also available.

References

[1] Ajduk et al, 2011, doi.org/10.1038/ncomms1424 [2] Kaouri et al, 2019, link.springer.com/article/10.1007/s00285-019-01333-8 [3] Sanders et al, 2018, 10.3389/fcell.2018.00036 [4] Dupont et al, Models of Ca2+ signalling, Springer, 2016, https://doi.org/10.1007/978-3-319-29647-0
For informal enquiries, please contact GW4BioMed@cardiff.ac.uk
For project related queries, please contact the respective supervisors listed on the projects.

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