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UK DRI PhD Studentship - Epigenomic profiling of brain cell types relevant to disease


Department of Brain Sciences

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Dr A Nott Applications accepted all year round Funded PhD Project (European/UK Students Only)

About the Project

Applications are invited for a 3.5-year PhD studentship at the UK DRI Centre at Imperial College London in the research group of Alexi Nott. The studentship is fully funded, providing tuition fees (Home/EU rate) and a tax-free stipend. The project is available with an immediate start date and we anticipate the successful candidate will take up the studentship before October 2021. Applications will be considered until the position is filled. The student will be registered in the Department of Brain Sciences in Imperial’s Faculty of Medicine. The student will be based at Imperial’s new White City Campus, the Hub for convergent research. The candidate will be part of the UK DRI, working in the Nott group and under the supervision of Alexi Nott.


About the UK Dementia Research Institute

There are currently around 850,000 people with dementia in the UK. This is projected to rise to 1.6 million by 2040. The UK DRI at Imperial has been established to address a medical research area of the highest importance and future impact. As one of seven national centres of excellence embedded in major UK universities, we intend to transform the diagnosis, treatment and care of people with dementias. The Medical Research Council and charity partners the Alzheimer’s Society and Alzheimer’s Research UK have invested £290m in fulfilment of the ambition identified in the Prime Minister’s 2020 Challenge on Dementia.

About the Laboratory

The programme of Dr Alexi Nott is focused on understanding how the epigenome and chromatin architecture regulates cell type gene expression programmes in the healthy brain and during ageing and disease. We are approaching this challenge using next-generation sequencing of patient-derived brain tissue and stem cell-derived models of disease.

Background

Ageing is the highest risk factor for dementia, creating a major health crisis as the ageing population expands to one in five people in the UK by 2030. Genetic variants that increase the risk of ageing-associated diseases such as Parkinson’s disease and Alzheimer’s disease have been identified. The function of these disease-risk variants is largely unknown. They often reside outside of genes in DNA regions thought to regulate gene expression, called enhancers. Enhancers integrate environmental signals, resulting in gene expression programs that guide cell type-specific responses. The colocalization of disease-risk variants in enhancers suggest that enhancer function is critical for normal ageing and that enhancer dysfunction is a driver of disease. While enhancers are key for inferring cell type-specific gene expression programs, prior work has focused on bulk tissue, potentially masking epigenomic changes that occur in rare cell types. For example, microglia, the immune cells of the brain, have been implicated in ageing-associated disorders; however, they constitute only 5% of cells in the brain and have been difficult to detect by bulk tissue analysis.

The Project

This PhD project is focused on understanding how cell type-specific enhancer function drives brain physiology and ageing-related disease. We will utilize nuclei isolation approaches developed for the brain to examine the epigenome of cell types and cell states implicated in disease. Tissue will be utilized from postmortem brain banks and resected tissue archives. The candidate will use next-generation sequencing approaches, such as chromatin immunoprecipitation sequencing (ChIP-seq), CUT&Tag and ATAC-seq to identify cell type specific gene regulatory regions. Genome conformation assays will be used to identify the gene targets for these noncoding regulatory regions. Integrative analysis with publicly available genetic data will be used to identify potential disease-relevant regions. Select gene regulatory regions implicated in disease may be tested using iPSC-derived models of brain cell types together with CRISPR-mediated DNA editing. The ultimate goal of this project is to reveal cell type-specific gene networks and transcription factors important for brain ageing and highlight candidate targets that are dysregulated in disease. To facilitate scientific growth, PhD students will be given opportunities to work closely with a broad range of other scientists across the UK DRI and in external universities.

To Apply

For informal enquiries please contact Alexi Nott ().
For application, please send a full CV, stating your motivation for applying, your nationality, and the full contact details of two academic referees to

We regret that due to the large volume of applications received, we are only able to notify those shortlisted for interview. Applications will be considered until the position is filled.

Funding Notes

The award is for 42 months (full time) and covers course fees (Home/EU rate) and a tax-free stipend of £19,000 rising to £20,500. Applicants must hold (or obtain by registration) a First Class or an Upper Second Class degree (or equivalent overseas qualification) in either biomedical sciences, neuroscience, pharmacology, genetics, molecular biology, biochemistry or equivalent. Imperial would normally expect successful applicants to hold or achieve a Master's degree in a related field. Prior experience in genomics biology and/or bioinformatics is essential, and experience relating to neuroscience will be beneficial.


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