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  MSc By Research: T cell activation dynamics and the ageing decline of immunity


   School of Medicine, Medical Sciences & Nutrition

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  Dr Michael Morgan, Dr Debbie Wilkinson  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.

Immune function in mammalian species, including humans, declines during ageing and is multi-faceted. From a human health perspective, this poses a considerable challenge as people are living for much longer than in previous decades and centuries because of advances in medicine, nutrition, and public health. An unwell ageing population places huge pressures on health care systems. Therefore, an understanding of how the immune system ages, and how this decline can be slowed or prevented is a pressing global challenge. The Morgan lab at the Institute of Medical Sciences, University of Aberdeen, combines experimentation and computation to study how ageing and our genetic make-up combine to shape our immune systems.

Data in my lab indicates that an inhibitory immune checkpoint protein called CTLA-4 (Krummel & Allison, 1995) is up-regulated in older people, which may explain why their immune systems are less able to fight off pathogens. CTLA-4 is expressed on different types of T cells, including memory and regulatory cells. CTLA-4 works by grabbing a protein required for T cell stimulation on the surface of antigen presenting cells, called CD80, and brings it inside the T cell where it is degraded – a process called transendocytosis (Qureshi et al. 2011). Regulatory T cells express the highest levels of CTLA-4 however, it is also up-regulated on activated T cells. It is not known how ageing increased CTLA-4 affects transendocytosis and T cell activation.

In this project, the student will use a novel T cell stimulation system to investigate the impact of ageing on T cell function, activation, and responses between young and old people. They will use a combination of flow cytometry, fluorescent, confocal, and live cell time-lapse microscopy to investigate how ageing shapes T cells activation between young and old people. The objectives are to investigate (a) whether T cell activation is different between young and old people, (b) test if transendocytosis on regulatory and activated T cells is affected by ageing, and (c) resolve how genetic variants affect T cell activation, transendocytosis and function. This project will provide opportunities to develop cutting edge experimental and bioinformatic skills, including in image analysis and genetics. Depending on project progress, opportunities to generate and analyse single-cell RNA-sequencing data may arise.

This project would suit a student interested in microscopy, cell biology, immunology or interdisciplinary research that bridges experimentation and computation (no computational experience required).

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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 Mike Morgan ([Email Address Removed]) 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 [Email Address Removed]
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

• Vento-Tormo et al, Nature 2018, Single-cell reconstruction of the early maternal-fetal interface in humans.
• Efremova et al, Nature Protocols 2020, CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes.
• Jin et al, Nature Communications 2021, Inference and analysis of cell-cell communication using CellChat.
• Browaeys et al, Nature Methods 2020, NicheNet: modelling intercellular communication by linking ligands to target genes.
• Dann et al, Nature Biotechnology 2022, Differential abundance testing on single-cell data using k-nearest neighbour graphs.
• Stephenson et al, Nature Medicine 2021, Single-cell multi-omics analysis of the immune response in COVID-19.

Where will I study?