Investigating the relationship between the late onset Alzhimer's Disease risk genes APOE and PICALM. (UK Students Only) Cardiff

Closing Date

12 Jul 2024

Salary

Full UK fees & UKRI level minimum stipend of £19,237 per year for your living costs.

Address

UK DRI at Cardiff University, Cardiff, CF14 4XN

Duration

4 Years

About the job

Dementia is the biggest 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.

Alzhiemer's disease (AD) is a devastating, progressive neurodegenerative disease with no cures and very few therapies to slow the progression effectvely. In sporadic late onset AD (LOAD), which accounts for >99% of cases, the lack of mechanistic understanding of LOAD genetics is the major bottleneck to producing new AD drug targets. Numerous genome- wide association studies (GWAS) have independently identified APOE and PICALM as two of the most significant genetic risk factors for developing LOAD. Intriguingly upregulation of PICALM has been demonstrated to rescue APOE4 induced phenotypes as well as amyloid beta (Aβ) toxicity. In addition adverse genetic interaction of PICALM and APOE is associated with brain atrophy and cognitive impairment in LOAD. This demonstrates a relationship between these two important LOAD risk genes which has not yet been further explored. This studentship will help to understand the combinational effect of APOE and PICALM using human induced pluripotent stem cell (iPSC) models and use them to modulate PICALM levels to understand its therapeutic potential.

This project will be based in the lab of Dr Natalie Connor-Robson, an expert in iPSC models of neurodengeneration and the endocytic pathway, and Co-supervised by Prof. Julie Williams, a leader in the genetics of Alzheimer's Disease. The student will become ad specialist in neurodegenerative disease modelling, molecular biology and LOAD genetics through the course of this PhD.

The student will be embedded within the UK Dementia Research Institute at Cardiff University, one of 7 UK centres bringing together world-leading scientists to deliver a step-change in the scientific understanding of dementia, generating new targets for drug development, reinvigorating the therapeutic pipeline and helping to transform care. Our strategy is to build upon research strengths in dementia genetics, immunology, computational analytics, cellular and whole system modelling and neuroimaging to identify disease mechanisms and therapies for Alzheimer’s, Parkinson’s and Huntington’s diseases and other dementias.

Essential Criteria

Applicants should possess a minimum of an upper second class Honours degree, master's degree, or equivalent in a relevant subject.

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

This 4 year PhD studentship PhD will be generously funded by Alzheimer's Research UK. Open to all UK students without further restrictions - this includes EU students who have Settled or Pre-Settled status in the UK Full UK tuition fees.

Contact Information

To apply visit here.