Whole brain 4D functional imaging in transgenic zebrafish for the purposes of seizure detection and epilepsy research
Understanding epilepsy-associated changes in brain electrical signalling is critical to more precisely defining epileptic events, determining their underlying triggers and developing new treatments. Based around advanced in vivo imaging of zebrafish neural activity this exciting project will provide multidisciplinary training in a wide range of cutting edge bioscientific and analytical methodologies.
This exciting studentship will use transgenic zebrafish and advanced imaging to progress knowledge of seizure mechanisms and epilepsy. Epilepsy affects 1-2% of humans and arises when abnormal hypersynchronised brain activity (seizures) develops and repeatedly spreads through connected brain circuitry. For 20-30% of sufferers, existing antiepileptic drugs are ineffective, and understanding altered activity across wide brain areas is critical for more precisely defining epileptic events and developing new treatments. To facilitate this, we have combined a zebrafish model expressing a genetically-encoded Ca2+ sensor in all CNS neurons with cutting-edge imaging (light sheet microscopy, LSM).
Following exposure to chemicals that induce neural network hyperexcitability, LSM allows unprecedented, high resolution, 4-dimensional analysis of seizure networks in vivo. This approach has allowed us to begin demonstrating that convulsant drugs which target defined cellular mechanisms (e.g. receptors, ion channels, transporters) produce distinct drug-specific spatiotemporal patterns of neural activity.
The successful candidate will use this system to establish brain activity data for different classes of drugs that replicate seizures and epilepsy, analysing for similarities and differences between classes, and will determine region-to-region characteristics of how anticonvulsant drugs resolve convulsant activity. These activity patterns will then be linked with specific zebrafish behaviours from the extensive data set we have compiled over the last decade and translation between zebrafish and mammals assessed for the purposes of seizure detection.
The student will get outstanding training and expert supervision in a wide-range of core bioscientific methodologies (e.g. advanced bioimaging, in vivo neuropharmacology, and computational data mining). The supervisory team comprises: Prof. Tyler, who leads a large team focussed on fish physiology and ecotoxicology; Dr. Winter who develops drug safety/efficacy assays using zebrafish; and Prof. Randall a leading vertebrate neurophysiologist. The wider research environment incorporates experts in advanced imaging (Prof. Julian Moger) and computational image processing (Dr. Jeremy Metz).
Professor Charles Tyler, Bioscience (University of Exeter)
Dr Matthew Winter, Bioscience (University of Exeter)
Professor Andrew Randall, Bioscience (University of Exeter)
Location: University of Exeter, Streatham Campus, Exeter
About the award:
This project is one of a number which are funded within the Carlota Palmer PhD programme. This four-year programme, run under the auspices of the Centre for Biomedical Modelling and Analysis, will commence in September 2016. The studentships will provide funding for a stipend (currently £16,165 per annum), research costs and UK/EU tuition fees for four years. Further details can be found here: http://www.exeter.ac.uk/bma/phd/
Applicants should 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 or technology. Applicants with a Lower Second Class degree will be considered if they also have Master’s degree or have significant relevant non-academic experience. If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.0 in any section) by the start of the project (alternative tests may be acceptable, see http://www.exeter.ac.uk/postgraduate/apply/english/).