We are pleased to invite candidates to apply for our PhD studentship investigating the role of cell cycle protein regulation in preventing cell division errors that lead to infertility and miscarriage in women.
Background. Accurate cell division relies on the alignment of all chromosomes so that they segregate equally into two new daughter cells. Unfortunately, mammalian oocytes often divide before their chromosomes are properly aligned, producing eggs with abnormal numbers of chromosomes. In humans this is the number one genetic reason for failed pregnancy, miscarriage and developmental disabilities in babies and, is a major contributor to IVF failure. We wish to understand how chromosome alignment is regulated by cell cycle proteins in mammalian oocytes, enabling us to understand why some oocytes fail and others progress. This is of critical importance to the 70,000+ patients undergoing IVF each year in the UK.
Objectives and Experimental Approach. We aim to identify differences between competent and non-competent oocytes and to use this information to clinical advantage. Ultimately, this will minimise the need for repeated IVF cycles, and reduce the financial burden and physical and mental health problems associated with infertility treatments.
This project begins with discovery science, but allows rapid translation into clinically relevant findings. We will use the oocytes of younger and older mice (excellent models of lower and higher frequency chromosome division errors) to monitor the temporospatial regulation of ~30 key proteins involved in cell division, using a cutting edge single cell technology known as imaging mass cytometry (IMC). Following this, we will use live oocytes to fully characterise proteins that differ between populations of oocytes, using techniques such as fluorescent protein expression, protein knock down and confocal microscopy, aiming to ‘rescue’ oocytes that would otherwise be at risk of committing division errors.
Finally, towards the end of the project, the successful candidate will have the opportunity to extend these findings to human oocytes in collaboration with the Newcastle Fertility Centre.
Importantly, this project delivers training in an interdisciplinary skill set, cutting across specialist cell biology and advanced imaging techniques, through to single cell technologies, data analytics and informatics, and translational medicine. Training in oocyte manipulations will be provided by the primary supervisor (see links below), while training in confocal imaging, imaging mass cytometry and proteome data analysis will be provided by both the primary and secondary supervisor (see link below), and by our world class support teams (https://www.ncl.ac.uk/bioimaging/gallery/and https://www.ncl.ac.uk/fccf/
In addition, the student will join our Cell Division Biology Research Group (https://research.ncl.ac.uk/celldivisionbiology/
) as a member of a supportive team of PhD and Post-Doctoral scientist with similar interests, participating regularly in broad ranging group meetings and scientific symposia.
Primary Supervisor - https://research.ncl.ac.uk/celldivisionbiology/people/staffprofilesuzannemadgwick.html https://www.ncl.ac.uk/medicalsciences/research/groups/profile/suzannemadgwick.html#publications
Secondary supervisor - https://www.ncl.ac.uk/medicalsciences/research/groups/profile/jonathanhiggins.html#background
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website: http://www.dimen.org.uk/
• Levasseur MD, Thomas C, Davies OR, Higgins JMG, Madgwick S. Aneuploidy in oocytes is prevented by sustained CDK1 activity through degron masking in cyclin B1. Developmental Cell (2019).
• Thomas C, Levasseur MD, Harris RJ, Davies OR, Madgwick S. Synchronous chromosome segregation in mouse oocytes is ensured by biphasic securin destruction and cyclin B1-Cdk1. BIORXIV/2019/824763 (2019).