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Understanding the role of impairment in the autophagy-lysosomal pathway in order to develop medications for post-viral neurological dysfunction


   Cardiff School of Biosciences

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  Dr E Lloyd-Evans, Dr H Waller-Evans  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Several viruses require interaction with lysosomal proteins or autophagosomes in order to either facilitate infection of the host cell or ensure maturation and release. Lysosomal dysfunction most often manifests in organisms as either neurodegeneration or neurological decline that is almost always associated with impaired autophagy and clearance of damaged cellular organelles. Perhaps it is therefore unsurprising that consequences of viral infection often include prolonged hallmarks of neurological impairment that is sustained after the infection has been cleared. These include; the recent discovery that 1 in 3 Covid-19 patients manifest with neurological symptoms, HIV is associated with dementia, chicken pox in adults can subsequently cause long term peripheral nerve pain, polio virus impairs motor neuron function and cytomegalovirus is the most common viral cause of developmental neurological impairment. In all cases these viruses induce lysosomal or autophagosome-lysosome impairment, but the mechanisms underlying these cellular changes remain unclear.

The first aim of this project is to utilise our expertise in lysosomal cell biology to explore and identify lysosomal targets that underpin viral entry/egress and that induce cellular dysfunction in human iPSC derived neuronal models. The second aim is to identify viral effectors of lysosomal dysfunction and determine their impact on iPSC neuron function post-infection. The final aim is to utilise high throughput screening approaches to identify and develop small molecule candidates to restore cellular function in iPSC neurons post virus infection.

Self funded students with an interest in this project should contact the supervisors for further information prior to making an application.

Biological Sciences (4) Medicine (26)

Funding Notes

Student must provide their own funding for the full 3-4 years of the project.

References

In order to be considered you must submit a formal application via Cardiff University’s online application service. (To access the application system, click the ’Institution Website’ button on this advert).There is a box at the top right of the page labelled ‘Apply’.
Applicants should apply to the Doctor of Philosophy in Subject with a desired start date of year/year.
In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select the ‘self-funding’ option.

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