Epilepsy inducing mutation of the GABA-A receptor alpha 1 subunit (360G-Wellcome-202489_Z_16_Z)
We will investigate how a newly discovered mutation to the GABA-A receptor alpha 1 subunit gene (GABRA1) is causing epilepsy in a young child. A single mutation has been identified, which resides in the receptor's first transmembrane domain. This is near the previously identifed neurosteroid binding site from which endogenous neurosteroids can positively modulate GABA-A receptor activity. To investigate the implications of this mutation we have formulated the following aims that will be addressed using heterologous expression of GABA-A receptors in a cell line: 1. To establish the effect of the mutation on GABA concentration response curves and current voltage relationships for typical synaptic and extrasynaptic-type GABA receptors. 2. To determine if known allosteric modulators of GABA-A receptors are affected by the alpha1 subunit mutation. 3. To deduce if the expression levels and receptor mobility at the cell surface are affected by the alpha 1 subunit mutation. To achieve these goals, we will use a combination of patch clamp electrophysiology and single particle imaging techniques. This should establish whether the mutation is causing a gain- or loss-of function, or affects receptor trafficking.
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Grant Details
Amount Awarded | 2000 |
Applicant Surname | McLuckie |
Approval Committee | Internal Decision Panel for C&S |
Award Date | 2016-04-01T00:00:00+00:00 |
Financial Year | 2015/16 |
Grant Programme: Title | Vacation Scholarships |
Internal ID | 202489/Z/16/Z |
Lead Applicant | Mr Joshua McLuckie |
Partnership Value | 2000 |
Planned Dates: End Date | 2016-08-06T00:00:00+00:00 |
Planned Dates: Start Date | 2016-06-06T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |