National Doctoral Programme in
Informational and Structural Biology

Our laboratory is particularly interested in the structural basis of selective recognition of glutamate agonists and antagonists, and the subsequent mechanisms triggered by these interactions. Importantly, native-like ligand binding can be reproduced by domains which are separable from the membrane-associated parts of the receptor allowing more detailed analyses than with the membrane protein. By using site-directed mutagenesis and biochemical analysis of purified receptor proteins, we have identified the structures which are critical for ligand interactions in a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor. A more recent activity focuses on mapping the allosteric regulatory sites in the receptor. These studies may contribute to development of neuroprotective and other drugs acting at glutamate receptors.

The assembly of glutamate receptors from subunits, transport to cell surface, anchoring to synapses, and association with signalling machinery, are poorly understood events involving complex interactions with other proteins. With an interest in the mechanisms which underlie the specific assembly of so-called calcium-permeable AMPA receptors, a subclass of glutamate receptors, we are examining their constituent subunits and associated proteins. We hope these studies will help us understand the mechanims by which neurons employ the molecular composition of the receptors to build synapses with unique properties.

Major collaborators: Dean Madden (biphysics, X-ray crystallography, Heidelberg), Michael Pasternack (electrophysiology, Helsinki), and Mark Johnson (molecular modelling, Turku).