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Structural Basis of Gabapentinoid Drug Action (360G-Wellcome-202355_Z_16_Z)

Gabapentinoids are blockbuster drugs used to treat conditions including neuropathic pain and epilepsy. They act by binding alpha2delta voltage-gated Ca2+ channel subunits. The focus of this summer project is to investigate the structure of alpha2delta to help understand its role in presynaptic Ca2+ entry and reveal the molecular basis of gabapentinoid binding. We have developed constructs for alpha2delta expression in High5 insect cells and HEK293T eukaryotic cells. We will express and purify different regions of alpha2delta, taking advantage of enzymes at our disposal for modifying glycosylation and pre-protein cleavage. Co-crystallisation screens will be set up with natural and synthetic small molecules including pregabalin and gabapentin. Successful crystal hits will be tested for x-ray diffraction using an in-house x-ray source. In the final fortnight of reserach, the student will perform crosslinking coupled to mass spectrometry experiments to determine the interaction sites of different subunits within the calcium channel complex, depending on the progress of crystallisation experiments.

£2,000

01 Apr 2016

Grant details
Amount Awarded 2000
Applicant Surname Liu
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 202355/Z/16/Z
Lead Applicant Mr Chenge Liu
Planned Dates: End Date 2016-09-10T00:00:00+00:00
Planned Dates: Start Date 2016-07-11T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
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