Development of novel drug treatments for epilepsy
Epilepsy is a significant clinical disorder that affects ~1% of the global population. Unfortunately, at least one third of epileptics fail to respond to available drugs. A promising avenue for these resistant individuals is combinational therapy in which cocktails of two or more drugs are used. Although beneficial, how such cocktails influence neuronal activity is unknown.
One significant barrier to achieve an understanding is the availability of suitable model systems which allow rapid drug screening and electrophysiology in vivo. We are exploiting the fruitfly, Drosophila melanogaster, to rationally design combinatorial therapy to treat seizure. Flies, like mammals, can be stimulated to induce seizure and, moreover, many single gene mutants have been identified that lower threshold for induced seizures. Flies also offer the possibility to make recordings from identified neurons to allow a full mechanistic description of drug cocktail activity to be derived. This project will use Drosophila larvae as both a test-bed for drug cocktail screening and determination of drug cocktail activity within the CNS. The candidate will be trained in many aspects of electrophysiology (particularly whole-cell patch clamp), drug screening, seizure determination and fly genetics. The candidate will also be expected to work closely with other PhD students and Postdoctoral fellows who are also investigating the mechanistic basis of seizure using the fly as a model.
More information can be found at: http://personalpages.manchester.ac.uk/staff/Richard.Baines/
This project has a Band 2 fee. Details of our different fee bands can be found on our website. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website. Informal enquiries may be made directly to the primary supervisor.
• Lin WH, Gunay C, Marley R, Prinz A and Baines RA. (2012) Activity-dependent alternative splicing increases persistent sodium current and promotes seizure. J Neurosci. 32: 7267-7277.
• Marley R and Baines RA (2011) Increased Na persistent current contributes to seizure in the slamdance bang-sensitive mutation. J Neurophysiol. 106: 18-29