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Self funded BMS Project: RNA dysregulation in neurodegeneration


   York Biomedical Research Institute


About the Project

Applications accepted for PhD Only

Neurodegenerative diseases are characterised by progressive neuronal loss with no effective treatment available. With many RNA-binding/regulating proteins (RBPs) associated with various neurodegenerative diseases, it indicates that mis-regulation of RNA plays a key role in neurodegeneration. TDP-43 is a RBP constituting key pathology observed in 97% of motor neurone disease and ~40% of Frontotemporal Dementia cases. We reported the first disease-causing RNA-binding deficient mutation which sparks renewed interest and leads to further discussion of the involvement of TDP-43-mediated RNA regulation and nuclear aggregation in disease development. This project will fill in the essential area investigating the mechanistic links between RNA-binding and neurodegeneration by using cell model in vivo studies:

1) Transcriptome profiling of cells with CRISPR-Cas9 knocked-in TDP-43 mutations to reveal the impact of dR-TDP-43 in global transcriptome profile.

2) Functional study of key players identified above in cells to characterise the pathogenesis mechanism involved in TDP-43 proteinopathy and cytotoxicity.

3) In vivo validation of the mechanism in neuronal health and morphology using Drosophila model.

Overall, this project will provide better understanding of the involvement of TDP-43-mediated RNA invovlement in the pathogensis underlying neurodegeneration.

The York Biomedical Research Institute at the University of York is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Entry Requirements: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions. 

Programme: PhD in Biomedical Science (3 years)

Start Date: 1st October 2022

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Funding Notes

This is a self funded research project. Applicants need to have adequate funds to meet the costs of a self-funded research project including tuition fees and living expenses for the duration of the research programme.

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