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Developing advanced fluorescence microscopy to study the cellular phase of Alzheimer’s disease

Dementia Research Institute

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 in the UK DRI Centre at Imperial in the research group of Dr Yu Ye (

The project is based at Imperial’s new White City Campus, the Hub for convergent research.

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.

The laboratory

The fellowship programme of Dr Yu Ye is focused on the interplay between the ubiquitin-proteasome system (UPS) and amyloid proteins in biological systems. Using advanced fluorescence imaging techniques, the lab seeks to uncover the biochemical and cellular mechanisms of restricting or reversing protein aggregation, and how malfunction of the UPS system leads to neurodegenerative disorders.


The aggregation process of amyloidogenic proteins is a hallmark of several neurodegenerative disorders including Alzheimer’s (AD) and Parkinson’s disease (PD). The monomeric proteins assemble into oligomers in solution and, through further aggregation and structural rearrangement eventually form stable fibrils. Both oligomers and fibrils have been suggested to drive neuronal death and neurodegeneration. While aggregation mechanisms and pathways have been extensively studied, how these aggregated structures may be removed by biological mechanisms is less well-studied. We have recently shown that proteasomes may target both oligomers and fibrils in vitro, and that the ubiquitin-proteasome system is implicated in aggregate clearance in cells. Understanding the interplay between aggregates and proteasomes and how failure of proteasome functions may cause imbalance in protein homeostasis is important for developing novel therapeutic strategies against neurodegenerative disorders.

The project

This PhD project is focused on using advanced fluorescence imaging and single-cell patch clamp techniques to study how amyloid proteins and aggregates affect cellular degradative systems. The ideal PhD candidate will have a background in physics/biophysics/engineering/physical chemistry with prior experience in image analysis/coding (e.g. Matlab). First assembling the microscope and establishing innovative degradation reporter systems in vivo, the candidate will use these reporters to study how recycling of cellular proteins is affected by protein aggregation. Using fluorescence microscopy and electrophysiological techniques, the candidate will further apply these studies to AD- and PD-mimicking neurons and characterise potential impairment of biological systems (e.g. of proteasomes).

Studentship Details

Students will be registered in the Department of Brain Sciences in the Faculty of Medicine.
The award is for 42 months (full time) and covers course fees at the Home/EU rates (2020/21 fees £6,300 per annum) and a tax-free stipend starting at £19,000 per annum. Applicants must hold (or obtain by October 2020) a First Class or an Upper Second Class degree (or equivalent overseas qualification) in a Biological Sciences / biophysics discipline, and Imperial would normally expect successful applicants to hold or achieve a Master's degree in a related field. Prior experience in ubiquitin-proteasome system is not essential but experience with microscopy techniques and animal works would be preferred.
Non-EU applicants, if successful, will be responsible for payment of fees at the overseas rate (currently £39,600 per annum). Funding for overseas fees is not provided.

For informal enquiries please contact Dr Yu Ye (). For application, please send a full CV, stating your nationality, and the full contact details of two academic referees.
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 throughout the year.

Funding Notes

The award is for 42 months (full time) and covers course fees at the Home/EU rates (2020/21 fees £6,300 per annum) and a tax-free stipend starting at £19,000 per annum.
Non-EU applicants, if successful, will be responsible for payment of fees at the overseas rate (currently £39,600 per annum). Funding for overseas fees is not provided.

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