MSc by Research: Does the mis-regulation of the meiotic HORMA-domain protein induce genome instability?

About the Project

The MSc by Research programme at the University of Aberdeen is for students interested in a research-intensive master's degree. It is designed specifically to enhance your skills for a PhD or research career. You can find further information about our academic requirements and MSc by Research programme structure here.

Meiosis is a specialised cell division, which reduces the number of chromosomes in the daughter cells by half, thus enabling sexual reproduction. Central to meiosis are pairing and recombination of homologous chromosomes. The meiotic HORMA domain proteins are highly conserved meiosis-specific factors associated with the chromosome axis and involved in regulating homologous recombination. Indeed, HORMA domain proteins are important for pairing and synapsis of homologous chromosomes by coordinating meiotic double-stranded DNA break (DSB) formation with DNA repair, thus influencing the outcome of recombination. Importantly, variants in HORMADs have been identified in patients suffering from infertility, while dysregulation of HORMAD1 expression in humans is associated with cancer formation. The yeast meiotic HORMA domain protein is called Hop1. This project will investigate the evolutionary conservation of Hop1 function(s) using Schizosaccharomyces pombe meiosis as a model. S. pombe (fission yeast) is ideal for studying eukaryotic cell biology because it has a short life cycle, meiosis can be induced synchronously, and it shares many features with multi-cellular eukaryotes.

1) Which molecular and structural features of Hop1 are essential for its meiotic function(s) and how do they underpin its mode-of-action? The meiotic HORMA protein comprises several domains: in addition to the HORMA domain at the N-terminus, there are multiple checkpoint phosphorylation sites at the centre of the protein, and a Zn-finger domain at the C-terminus. To understand the importance of these, meiotic recombination, chromatin recruitment, and their interaction with cohesin will be characterised in mutants lacking a particular subdomain.

2) How does the mis-expression of Hop1 impact on DNA metabolism in vegetative yeast cells? Intriguingly, Hop1 seems to be able to confer some of its function(s) in steering recombination away from sister chromatids to homologous chromosomes without being recruited to chromatin, a property with the potential to induce inappropriate recombination events in mitotic cells and thus drive cancer formation. This possibility will be examined by inducing expression of yeast Hop1 and mammalian HORMAD1 in vegetative yeast cells and testing mitotic recombination.

In addition to the scientific goals this MSc by Research project will deliver formative training for an early-career researcher in advanced genetics and molecular cell biology methods.

Informal enquiries are encouraged and can be directed to Dr Alexander Lorenz (a.lorenz@abdn.ac.uk).

Candidate Background:

We actively encourage applications from diverse career paths and backgrounds and across all sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation and transgender status, amongst other protected characteristics.

We also invite applications from those returning from a career break, industry or other roles. We typically require a minimum of a 2:1 UK Honours degree (or equivalent), but exceptions can be made where applicants can demonstrate excellence in alternative ways, including, but not limited to, performance in masters courses, professional placements, internships or employment.

APPLICATION PROCEDURE:

• Please note: This is a self-funded opportunity only.
• Prospective students should contact the lead supervisor (via the email address listed above) to discuss the research project and complete a proposal form prior to / or shortly after applying.
• Formal applications can be completed online: https://www.abdn.ac.uk/pgap/login.php
• You should apply for Medical Sciences (MSc) to ensure your application is passed to the correct team.
• Please clearly note the name of the supervisor and the project title on the application form.
• Your application must include: a personal statement, an up-to-date copy of your academic CV, and clear copies of your educational certificates and transcripts.
• If you are still undertaking your undergraduate degree, it is helpful to the selection panel if you could provide documentation showing your grades to date (this can be a screenshot from an online portal).
• Please note: Project supervisors will not respond to requests for funding assistance.
• If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at pgrs-admissions@abdn.ac.uk

Funding Notes

This is a self-funding project open to students worldwide. Our typical start dates for this programme are October/ February, however we may be able to accommodate start dates in other months if this is preferred.

Fees for this programme are currently £5,006 for home/UK students, and £27,300 for international students.

Additional research costs/bench fees of £3,000 will also apply to the MSc by Research programme.