Investigation the role of p62-dependent P-bodies in models of neurodegeneration

Director of Studies: Dr Holly Stephenson

2^nd Supervisor: Professor Shouqing Luo 

3rd Supervisor:  Dr Claudia Barros 

Applications are invited for a three-year PhD studentship. The studentship will start on 1 October 2024.  

Neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), are a group of conditions characterised by the progressive degeneration of the structure and function of the nervous system, collectively affecting more than 50 million people worldwide. Neuroinflammation, potentially triggered by infection, proteotoxic and oxidative stress, is heavily implicated in the pathogenesis and progression of neurodegenerative disorders. 

Macroautophagy, commonly known as autophagy, functions as a lysosomal degradation system responsible for eliminating aberrant cytoplasmic components. Within the autophagy process, SQSTM1/p62 assumes a crucial role by serving as a receptor that facilitates the selective autophagic removal of specific substrates. Currently, the existence of alternative forms of p62 beyond autophagic droplets remains unknown. Mutations in p62 are associated with multiple neurodegenerative diseases, including ALS and FTD. 

This PhD project aims to investigate the link between p62 and ribonucleoprotein (RNP) granules, such as P-bodies, a dynamic category of membrane-less biomolecular assemblies consisting of RNAs and RNA binding proteins (RBPs) induced by multiple stimuli, including infection, oxidative and proteotoxic stress conditions. Aberrant formation of RNP granules is associated with several neurodegenerative diseases and we recently discovered the importance for p62-dependent P-body formation in regulating inflammatory responses (Barrow et al., 2024). In this project drosophila will be used as model organism for investigating the functionality of p62/RNP interactions in models of neurodegeneration in vivo, including AD and ALS. Furthermore, their role in driving a pro-inflammatory state that promotes neurodegeneration will be determined. 

We are looking for a highly motivated student with a first or upper second class honours degree in an appropriate subject or a relevant masters qualification (biological sciences). If your first language is not English, you will need to meet the minimum English requirements for the programme, IELTS Academic score of 6.5 (with no less than 5.5 in each component test area) or equivalent. 

The studentship is supported for three years and includes full home tuition fees plus a stipend of £18,110 per annum 2023/24 rate (2024/25 rate TBC).  The studentship will only fully fund those applicants who are eligible for home fees with relevant qualifications.  Applicants normally required to cover international fees will have to cover the difference between the home and the international tuition fee rates (approximately £12,697 per annum 2023/24 rate). 

NB: The studentship is supported for three years of the four-year registration period. The fourth year is a self-funded ‘writing-up’ year.

If you wish to discuss this project further informally, please contact Dr Holly Stephenson.

Please see our apply for a postgraduate research programme page for a list of supporting documents to upload with your application. 

For more information on the admissions process generally, please visit our apply for a postgraduate research programme page or contact the Doctoral College at research.degree.admissions@plymouth.ac.uk.

Shortlisted candidates will be invited for interview shortly after the deadline. We regret that we may not be able to respond to all applications. Applicants who have not received a response within six weeks of the closing date should consider their application unsuccessful on this occasion.