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EASTBIO: Developing a novel integrated molecular and biomechanical approach for oocyte quality selection


   MRC Centre for Reproductive Health

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  Dr C-J Lin, Dr Pierre Bagnaninchi  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Approximately one in seven couples have difficulty conceiving. People affected by infertility often suffer from impaired physical and mental health arising from their inability to start a family. It is widely accepted that one of the major factors contributing to female infertility is oocyte quality (developmental competence) result from either misregulated (epi)genetic mechanisms during oogenesis or due to maternal ageing. Despite Assisted Reproductive Techniques being routinely carried out in IVF clinics, an accurate, non-invasive predictor for selecting high-quality oocytes and predicting embryonic/pregnancy outcome is still lacking.

This project has been conceived by the interdisciplinary collaboration of Dr Lin with Dr. Bagnaninchi. Recently, the Lin lab has generated a new animal model of infertility, Cabin1 oocyte-specific conditional knockout mice (Smith et al., 2021 Reproduction and Smith et al., 2022 Development). Oocytes derived from Cabin1 mutant mice revealed developmentally incompetent signatures which offer an excellent model for studying oogenesis and early embryogenesis. Meanwhile, the Bagnaninchi lab has developed a novel optical methodology for 3D measurement of biomechanical properties. Intriguingly, the preliminary result showed that after combining the above cutting-edge developments, incompetent Cabin1 mutant oocytes exhibited a distinct profile when compared to the controls (doi: https://doi.org/10.1101/2021.05.12.443111). This suggests that this approach can be an effective tool for screening and selecting oocytes with particular characteristics.

In this project, our first aim is to refine the optical elastography system using a new state-of-art nanoindenter device to grade both incompetent Cabin1 and aged oocytes by profiling various micro-mechanical properties. Our next aim is to collate our existing transcriptomic and epigenomic data and correlate it with the 3D measurements to explore the causes of the biomechanical disruptions.

This project will provide distinctive interdisciplinary training covering biomedical engineering, advanced imaging, molecular biology, epigenetics, mouse genetics, and Assisted Reproductive Techniques. The overarching aim is to apply this technology to provide better assessments of oocyte quality. Potentially, it could be used as an adjunct to existing time-lapse and imaging culture systems to offer a high-resolution, non-invasive route to further improvements in IVF clinical practice.

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training, beginning in the 2023-2024 academic year.

Please refer to the UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.

Applicants are expected to have a good honours degree in the sciences (biological, chemical or physical), at least UK level of 2.1 or the equivalent from non-UK universities and meet the English language entry requirements. A Master’s degree in a relevant subject would be an advantage.

EASTBIO Application and Reference Forms can be downloaded via  http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO Application Form along with a copies of your academic degree/transcripts to [Email Address Removed].

You should also ensure that two references have also been sent to [Email Address Removed] by the deadline using the EASTBIO Reference Form.


Funding Notes

This opportunity is open to UK and international students and provides funding to cover stipend and UK level tuition fees. The University of Edinburgh will cover the difference between home and international fees meaning that the EASTBIO DTP will offer fully-funded studentships to all appointees. However there is a cap on the number of international students the DTP can recruit. It is therefore important for us to know from the outset which fees status category applicants will fall under when formally applying for entry to our university.

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