Prof R Baines, Prof Matthew Cobb
No more applications being accepted
Competition Funded PhD Project (Students Worldwide)
About the Project
Prof Richard Baines of Manchester University and Dr Adam Claridge-Chang of A*STAR, Singapore are offering an exciting doctoral project to identify novel anticonvulsant compounds for the analysis and treatment of epilepsy. Doctoral research will be conducted in both Manchester (years 1 and 4) and Singapore (years 2 and 3).
Current antiepileptic drugs are effective for only two-thirds of patients and are associated with significant side-effects. Better drugs are needed, but a lack of novel drug targets and good screening methods are significant barriers. The fruit fly (Drosophila melanogaster) offers the prospect to develop high-throughput screens to identify novel anticonvulsant compounds. Single gene mutations exist that increase the severity and duration of induced seizures in flies; seizures that respond well to treatment using existing antiepileptic drugs. This, and other studies, shows that the underlying biological basis of seizure in flies is remarkably similar to humans.
In the first year, you will learn to work with Drosophila seizure mutants, using behavioral methods and calcium imaging to observe activity of central neurons. In the second year, you will implement advanced behavioral analysis methods (machine vision) to quantify seizure severity and dynamics. In the third year, you will use the behavioral analysis systems to screen for novel anticonvulsant compounds. These will include venom peptides that may block voltage-gated sodium channels and/or other excitatory ionic currents. In the final year, you will apply calcium-imaging and electrophysiology to determine mode-of-action for interesting anticonvulsant compounds identified.
This is an interdisciplinary research project that combines the quantitative analysis of seizure behaviours, drug-screening and in vivo physiology in Drosophila seizure models. As an ideal candidate, you would need to have an interest in epilepsy causes and treatments, along with the aptitude to learn a range of experimental techniques spanning neurogenetics, neurophysiology, computer-aided imaging and testing of compounds in whole-animal seizure screens. Both labs offer conscientious scientific mentorship, rigorous technical training and highly collaborative environments.
Funding Notes
The project is available to UK/EU candidates. Funding covers fees (UK/EU rate) and stipend for four years. Overseas candidates can apply providing they can pay the difference in fees and are from an eligible country. Please check the website for information on eligibility. Candidates will be required to split their time between Manchester and Singapore, as outlined on our website. Applications should be submitted online and candidates should make direct contact with the Manchester supervisor to discuss their application directly.
References
1.Streit AK, Fan YN, Masullo L and Baines RA (2016) Calcium imaging of neuronal activity in Drosophila can identify anticonvulsive compounds. PLOS One DOI:10.1371/journal.pone.0148461 February 10, 2016.
2.Giachello CNG and Baines RA (2015) Inappropriate neural activity during a sensitive period in embryogenesis results in persistent seizure-like behaviour. Curr. Biol. 25:2964-2968.
3.Lin WH, He M and Baines RA (2015) Seizure suppression through manipulating splicing of a voltage-gated sodium channel. Brain 138:891-901.
4. Alnabulsi S, Santina E, Russo I, Hussein B, Kadirvel M, Chadwick A, Bichenkova EV, Bryce RA, Nolan K, Demonacos C, Stratford IJ, Freeman S (2016) Non-symmetrical furan-amidines as novel leads for the treatment of cancer and malaria. Eur. J. Med. Chem.111:33–45.
5. Emsley HC, Appleton RE, Whitmore CL, Jury F, Lamb JA, Martin JE, Ollier WE, de la Morandière KP, Southern KW and Allan SM (2014) Variations in inflammation-related genes may be associated with childhood febrile seizure susceptibility. Seizure 23:457-61
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