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  (MRC DTP) Exploiting Drosophila to identify novel causes of, and treatments for, epilepsy in human


   Faculty of Biology, Medicine and Health

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  Prof R Baines, Dr S Banka, Prof Stuart Allan, Dr Robert Wykes  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Epilepsy is amongst the most common neurological diseases, affecting greater than 1% of the population. Clinical treatment relies on the use of a range of anti-epileptic drugs that are successful in no more than two-thirds of patients. A primary reason for this shortfall is the large number of underlying genetic mutations that are associated with epilepsy; only a handful of which have been characterised. To speed progress in characterisation of epilepsy-related genes, and to develop better treatments, we will utilise the fruit fly Drosophila melanogaster, to model the mutations we identify and use behavioural testing to determine contribution to seizure severity and response to drug treatment. Drosophila has long been used to study the mechanistic basis of seizures and many seizure-associated genes identified in this insect are well conserved in humans. Drosophila seizure mutants also respond remarkably well to antiepileptic drugs used in the clinic.

This project brings together four research leads that have expertise spanning 1) the identification of novel epilepsy-associated genes in human patients, 2) the use of Drosophila to study seizure and seizure-suppressing drugs, 3) Drosophila molecular biology and 4) mouse genetics and seizure assays. The appointed individual will benefit from this grouping allowing novel mutations, identified in the clinic, to be modelled in flies to determine their contribution to seizures and which of the many available anti-epileptic drugs are most effective. For some mutations, we will explore translational viability of effective drugs via development of suitable intermediate mouse transgenic models. Training will be provided in a variety of cross-disciplinary techniques, ranging from genetics spanning humans to flies, molecular biology, behavioural seizure assays (flies and mice) and drug delivery and drug testing.

https://www.research.manchester.ac.uk/portal/richard.baines.html

Entry Requirements

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships 

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

Biological Sciences (4) Medicine (26)

Funding Notes

Funding will cover UK tuition fee and stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1.Lin WH and Baines RA (2019) Myocyte enhancer factor-2 and p300 interact to regulate expression of the homeostatic regulator Pumilio in Drosophila. Eur. J Neurosci.
2.Lin WH, He M, Fan YN and Baines RA (2018) An RNAi-mediated screen identifies novel targets for next-generation
antiepileptic drugs based on increased expression of the homeostatic regulator Pumilio. J Neurogentetics.
3. Vaz FM, … Banka S. Mutations in PCYT2 disrupt etherlipid biosynthesis and cause a complex hereditary spastic paraplegia. Brain. 2019 Nov 1;142(11):3382-3397.
4. Snowball A, Wykes RC et al 2019. Epilepsy Gene Therapy Using an Engineered Potassium Channel. Journal of Neuroscience.
5. Qu, Y., Hahn, I., Lees, M., Parkin, J., Voelzmann, A., Dorey, K., Rathbone, A., Friel, C., Allan, V., Okenve Ramos, P., Sánchez-Soriano, N., Prokop, A. (2019). Efa6 protects axons and regulates their growth and branching by inhibiting microtubule polymerisation at the cortex. eLife 8, e50319
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