MSc By Research: Does Rif1 affect meiotic recombination and chromosome segregation in Schizosaccharomyces pombe?


   School of Medicine, Medical Sciences & Nutrition

  ,  Applications accepted all year round  Self-Funded PhD Students Only

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. If you have your own ideas for a research project in this area, we would love to hear from you! Please reach out to one of the project supervisors above to discuss your ideas.

You can find further information about our academic requirements and programme structure here.

The mitotic cell cycle, characterized by DNA replication followed by cell division, plays a pivotal role in maintaining cellular health and integrity. Any dysregulation of this process can lead to the development of cancer. In particular, the S-phase of the cell cycle, where DNA replication occurs, is a critical phase in ensuring the accurate transmission of genetic information to daughter cells.

Meiosis, on the other hand, is a specialized form of cell division that produces gametes necessary for sexual reproduction. Despite its similarities with the mitotic cell cycle in terms of control mechanisms, pre-meiotic S-phase progresses more slowly. This extended duration of pre-meiotic S-phase is attributed to reduced efficiency in origin firing and slow replication fork progression, the precise regulation of which remains elusive.

Rap1-interacting factor 1 (Rif1) has been well-characterized as a key regulator of mitotic S-phase, but its role in meiotic processes is not yet fully understood. Initially identified as a telomere-binding protein with a role in telomere length regulation, Rif1 has been recognized as a master regulator of DNA replication timing. Additionally, Rif1 is involved in chromosome organization, preventing DNA entanglements, and contributing to DNA damage signaling and repair pathways, crucial for preventing cancer formation. In meiosis, Rif1 may play a significant role in controlling DNA double-strand break (DSB) repair pathway choice, a process essential for proper chromosome segregation.

Despite its established importance in mitotic DNA replication and chromosome organization, the roles of Rif1 in meiosis remain enigmatic. This research proposal aims to address these knowledge gaps using the model organism Schizosaccharomyces pombe (fission yeast), which is highly relevant for studying meiotic processes.

Objective 1: Investigate the Effects of Rif1 Deficiencies on Meiotic Recombination

To determine whether Rif1 directly influences meiotic recombination or indirectly affects it due to alterations in pre-meiotic S-phase, we will utilize various rif1 mutants generated through the CRISPR-Cas9 system.

Objective 2: Assess the Impact of Rif1 Absence on Meiotic Chromosome Pairing and Segregation

Chromosome pairing and segregation during meiosis are intricately linked to recombination and the cohesin complex. We will investigate whether the absence of Rif1 leads to changes in cohesin distribution, and chromosome pairing & segregation, and how these alterations impact recombination outcomes and gamete viability.

This project employs cutting-edge genetics and cell biological techniques to elucidate the meiotic role(s) of Rif1, a key regulator of DNA replication and repair. By addressing fundamental questions regarding the influence of Rif1 on meiotic recombination, chromosome dynamics, and gamete viability, this research contributes to a deeper understanding of the molecular mechanisms governing meiosis. Furthermore, these findings may have broader implications for our understanding of cell cycle regulation and cancer prevention.

In conclusion, this research proposal outlines a comprehensive investigation into the meiotic functions of Rif1, shedding light on its role in maintaining genomic stability and ensuring accurate chromosome segregation during meiosis. Through rigorous experimentation and analysis, we aim to advance our knowledge of Rif1's contributions to meiotic processes, providing insights with potential implications for human health and disease prevention.

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Applicants to this project should hold a minimum of a 2:1 UK Honours degree (or international equivalent) in a relevant subject.

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.

Informal enquiries are encouraged, please contact Dr Alexander Lorenz () for further information.

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APPLICATION PROCEDURE:

Please note: This is a self-funded opportunity.

  • 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. If this is not included, your application may not be considered for the project.
  • Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree (or international equivalent) at undergraduate level.
  • 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 
Biological Sciences (4) Medicine (26)

Funding Notes

This is a self-funding project open to students worldwide. Our typical start dates for this programme are February or October.
Fees for this programme are £4,712 for home/UK students, and £24,860 for international students.
Additional research costs / Bench fees of £3,000 will also apply.
The Scottish Government offers postgraduate loans to those due to start a Masters (taught or research) programme.

References

1)Lorenz A, Mpaulo SJ (2022) Gene conversion: a non-Mendelian process integral to meiotic recombination. - Heredity 129 (1): 56-63
2)Brown SD*, Mpaulo SJ*, Asogwa MN, Jézéquel M, Whitby MC, Lorenz A (2019) DNA sequence differences are determinants of meiotic recombination outcome. - Scientific Reports 9: 16446 (10pp.) (*these authors contributed equally)
3)Li D, Roca M, Yuecel R, Lorenz A (2019) Immediate visualization of recombination events and chromosome segregation defects in fission yeast meiosis. - Chromosoma 128 (3): 385-396

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