Scheme: University Research Fellowship
Organisation: University of Cambridge
Dates: Oct 2008-Sep 2011
Summary: Glutamate-gated ion channels (iGluRs) mediate the majority of excitatory synaptic signaling in the brain. Operation of these receptors underlies higher-order cognitive processes such as learning and memory. Malfunction of iGluRs can contribute to a wide range of acute and chronic neurological disorders, including stroke, ischaemia, amyotrophic lateral sclerosis and neurodegeneration. Functional properties of the receptor are shaped by different subunit compositions, which are established from a set of core subunits in a largely unknown process. Our work aims to identify the mechanism underlying subunit assembly at high resolution in atomic detail. We have revealed the molecular signatures of subunit interfaces and critical hotspots in interfaces that are central to the assembly process. Secondly, we have shown that genetic switches located at subunit interfaces can respond to alterations in neuronal activity and mediate a dynamic remodeling of these receptors. This regulation facilitates adaptations of neurons to specific physiological activity patterns.
Dates: Sep 2003-Sep 2008
Summary: This project summary is not available for publication.