Deciphering the role of genetic variation on natural killer cell function at University of Edinburgh on FindAPhD.com

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Prof J Hope, Dr Inga Dry, Dr John schwartz, Prof John Hammond No more applications being accepted Competition Funded PhD Project (Students Worldwide)

Edinburgh United Kingdom Immunology

College of Medicine and Veterinary Medicine, University of Edinburgh

About the Project

Natural killer (NK) cells are cytotoxic and cytokine producing lymphocytes key to the anti-viral immune response. These cells are also known to be important in driving protective immune responses in both cattle and humans following vaccination against tuberculosis with BCG.

The activity of NK cells is regulated through a balance of activating and inhibitory receptors that are often highly diversified and bind to equally diverse major histocompatibility complex class I (MHC-I) ligands. Ruminants are unique amongst species studied as they exhibit multiple receptor family expansions. Genomic, genetic, and functional studies over several years all point to specific receptors encoded with the natural killer complex (KLRC/D and KLRH) as being the primary regulators of NK cell function.

We hypothesise that individual KLRC/D and/or KLRH receptors will bind specific MHC-I allele groups. This project aims to identify and characterise receptor/ligand interactions and how these initiate and control immune responses. We will assess the role of NK cells and these receptor ligand pairs in infection studies with bovine respiratory syncytial virus and bovine herpes virus-1. We will also extend our understanding of the role of NK cells in the protective immune response induced by the BCG vaccine.

This is a collaborative project between the Pirbright and Roslin Institutes where extensive expertise in identification of receptor-ligand interactions and innate immune mechanisms currently exists. We will use a range of in silico, in vitro and in vivo methods to address the hypothesis.

Funding Notes

This 3.5 year studentship opportunity is open to UK and international students and provides funding to cover stipend, tuition fees and consumable/travel costs. Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [Email Address Removed].
When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.
We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 4th January 2023 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships

References

1. The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation. Schwartz JC, Gibson MS, Heimeier D, Koren S, Phillippy AM, Bickhart DM, Smith TP, Medrano JF, Hammond JA. Immunogenetics. 2017 Apr;69(4):255-269. doi: 10.1007/s00251-017-0973-y
2. Interactions between natural killer cells and dendritic cells favour T helper1-type responses to BCG in calves. Hamilton CA, Mahan S, Entrican G, Hope JC. Vet Res. 2016 Aug 17;47(1):85. doi: 10.1186/s13567-016-0367-4.
3. Cattle NK Cell Heterogeneity and the Influence of MHC Class I.
Allan AJ, Sanderson ND, Gubbins S, Ellis SA, Hammond JA.J Immunol. 2015 Sep 1;195(5):2199-206. doi: 10.4049/jimmunol.1500227.

Where will I study?

University of Edinburgh

One of the world''s top universities, consistently ranked in the world top 50 and placed 20th in the QS World University Rankings 2020. We provide a stimulating working, learning and teaching environment with access to excellent facilities and attract the world''s best, from Nobel Prize winning laureates to future explorers, pioneers and inventors.