(MRC DTP) Modelling novel epilepsy-associated mutations in Drosophila

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, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

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