PhD Studentship: Determining the HLA association in Alzheimer’s disease and its impact on antigen presentation

An individual's risk for developing Alzheimer’s disease (AD) is partially determined by changes in their genes. Small changes in specific genes increase the risk of developing AD. Genetic analysis of large cohorts of individuals have reported an association with variants in human leukocyte antigen (HLA) genes and AD. An individual’s HLA genotype determines how the immune response recognises and responds to different antigens in different individuals and variants in HLA have been reported as major risk factors for complex diseases. Within the brain, HLA genes are predominantly expressed on the surface of microglia and present peptides to T-cells. Due to the highly polymorphic nature of HLA genes, the strong linkage disequilibrium and the population-specific genetic diversity determining the exact genetic variants responsible for influencing disease risk is complex, and how an individual’s HLA makeup drives AD aetiology remains to be explored.

This studentship will use a range of bioinformatic and wet lab approaches and be based in the lab of Dr Sarah Carpanini (iPSC) and co-supervised by Dr Rebecca Sims (bioinformatician). The student will use induced pluripotent stem cell (iPSC) models of microglia with different HLA genetics to explore whether variants in HLA alter microglial antigen presentation in AD.

This will improve our understanding of how the HLA genes influence risk for AD, which HLA genes are most important in AD, and how these HLA genes affect microglia function. Understanding the genes influencing AD allows us to identify those at risk and assist in developing new drug treatments.

The student will gain expertise in neurodegenerative disease modelling, molecular biology and genetics and be based in the UK Dementia Research Institute (DRI) at Cardiff University. 

Entry Requirements  

You will hold or expect to achieve a First or Upper Second Class degree in biomedical science, biochemistry, cell biology or a related subject. As this is a training doctorate, previous research experience is not essential.

Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS).