Using microRNA inhibitors to boost GABAergic inhibition as a genetic therapy for epilepsy

Epilepsy is a chronic neurological disease characterised by recurrent spontaneous seizures and cognitive co-morbidities. Current small molecule approaches to treating epilepsy are ineffective in a significant portion of cases, and are associated with substantial adverse effects. MicroRNAs are a class of noncoding RNAs which modulate the expression patterns of our genes and shape the transcriptomic landscape in the brain. MicroRNAs play key roles in brain function in health and disease, and have been shown to modulate brain excitability via various mechanisms. This project sets out to develop microRNA-based nucleic acid and gene therapies which treat epilepsy by boosting inhibitory signallling pathways.

This project, at the intersection of cutting-edge electrophysiology and molecular biology, seeks to reveal new molecular mechanisms which shape inhibitory signalling, brain excitability and epilepsy.

You will use ex vivo and in vivo electrophysiological techniques ranging from the single-cell level (patch clamp) to the network level (multi-electrode arrays and EEG), combined with molecular (RT-qPCR) and imaging techniques, to determine the effect of antisense oligonucleotide microRNA inhibitors in epilepsy models. You will be supervised by three leading experts in the field, who will provide high-level multidisciplinary training in all of the techniques required, and you will join an internationally-renowned scientific community within the Division of Neuroscience at the University of Manchester.

Training/techniques to be provided

Morris: ex vivo brain slice electrophysiology (patch clamp, dynamic clamp, LFP recording), immunofluorescent imaging, microscopy, data analysis, statistics, hippocampal physiology, pathophysiology of epilepsy

Wykes: in vivo seizure/epilepsy models, surgical techniques, animal welfare and husbandry, in vivo electrophysiology, data analysis, statistics, pathophysiology of epilepsy

Baines: gene expression analysis (Western blot, RT-qPCR), data analysis, statistics, pathophysiology of epilepsy

Entry Requirements

Candidates will ideally hold an MSc degree (or equivalent) in neuroscience, or in a related discipline. Motivated candidates from a neuroscience background with a minimum upper second class honours degree are also encouraged to apply.

It is desirable that candidates have experience of electrophysiology and/or gene expression analysis and/or working with laboratory rodents.

How to Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD Neuroscience.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/international/

Enquiries to: gareth.morris-3@manchester.ac.uk .

Equality, Diversity & 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/