PhD Studentship (Cardiff)

Closing Date
26 Nov 2021
Salary
Tuition fees, plus £15,609 per annum stipend (updated each year) and research training and support fund of up to £5K.
Address
Cardiff University
Duration
3.5 years

Dementia is the greatest health challenge of our century. To date there is no way to prevent it or even slow its progression, and there is an urgent need to fill the knowledge gap in our basic understanding of the diseases that cause it. The UK Dementia Research Institute (UK DRI) is the biggest UK initiative driving forward research to fill this gap. They are a globally leading multidisciplinary research institute of 700 staff investigating the spectrum of neurodegenerative disorders causing dementia, with laboratory-based research groups located at University College London, the University of Cambridge, Cardiff University, Edinburgh University, Imperial College London and King’s College London. Rapid advances in DNA technologies and computational biology are enabling scientists to identify more and more of the subtle DNA variations that can influence a person’s risk of developing different neurodegenerative diseases. Researchers at the UK DRI at Cardiff interrogate the host of genetic variations linked with neurodegenerative diseases to make new discoveries about disease processes. They use experimental model systems along with a variety of cutting-edge experimental methods and equipment to dissect the biology of many of these genes. Building on the team’s international reputation for complex data analyses, they develop and apply advanced computational approaches that enable them to make sense of huge datasets generated by complex experiments.

 

Project title: Epigenetic regulation of microglial gene expression in Alzheimer’s disease

Neuroinflammation is emerging as a key pathogenetic event in risk and progression of Alzheimer’s disease (AD). Genome wide association studies have identified single nucleotide polymorphisms (SNPs) at genetic loci associated with microglia function enriched in AD patient cohorts, however precisely how these alter gene expression within loci is often unclear. Profiling transcriptional regulation of AD associated gene by epigenome wide association studies of post-mortem human cortex has identified enriched patterns of DNA methylation in microglial genes of AD patients. Whilst further illuminating the contribution of microglia in AD pathogenesis, a caveat of these experiments is the tissue utilised; post-mortem samples of mixed cell types derived from patients dying with late-stage AD with profound neurodegeneration and inflammation. Such tissues may not capture more subtle, early changes in epigenomic regulation. To better understand these events, we will profile the epigenome of human microglia in an in vitro cell culture model of AD, hypothesising that essential microglial functions are disrupted through altered epigenetic regulation of microglia specific genes in AD.

Applicants for a studentship must have obtained, or be about to obtain, a UK degree, or the equivalent qualification gained outside the UK, in an appropriate area of medical sciences. However, the DTP also welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences.