4 YEAR PhD IN NEUROSCIENCE
Ion channels and disease
Changes in ion channels lead to diseases, such as epilepsy, migraine and chronic pain syndromes. Likewise diseases can lead to changes in ion channels – altering their expression, splicing and function. We are interested in both directions of change.
The lab combines molecular biology (from quantitative RT-PCR from single neurons to promoter construction in lentivirus constructs) and electrophysiology (in cell lines, cultured neurons and in slices). Students can expect to learn how to clone their favourite channel, express it, and to probe its function in cells and neurons.
Accessorising sodium channels: Sodium channels are thought to contain accessory subunits, but in many cases the effects of the accessories are unknown. This is a project focused on electrophysiology, in non-neuronal cells (where the combinations of subunits can be controlled) and in neurons (where accessories can be manipulated with virally-delivered shRNAs).
Finding sodium channel splice variants: Sodium channel splicing changes in epilepsy, and is associated with different response to anti-epileptic drugs. We have new antibodies that distinguish between channel splice variants. This project involves immunohistochemistry, and electrophysiology.
Genetics of epilepsy: We have identified polymorphisms in new ion channel genes that are enriched in families with epilepsy. This project involves genetic analysis as well as cloning and heterologous expression of mutant channels.
Schorge S, van de Leemput J, Singleton A, Houlden H, Hardy J. (2010)
“Human ataxias: a genetic dissection of inositol triphosphate receptor (ITPR1)-dependent signaling.”
Trends Neurosci. 33(5):211-9
Rajakulendran S, Graves TD, Labrum RW, Kotzadimitriou D, Eunson LH, Davis MB, Davies R, Wood N, Kullmann DM, Hanna MG, Schorge S. (2010)
“Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy.”
J Physiol. 588(Pt 11):1905-13
Schorge S & Colquhoun D (2003)
“Studies of NMDA Receptor Function and Stoichiometry with Truncated and Tandem Subunits”
Journal of Neuroscience 23(4):1151–1158