Native structure and gating of glutamate receptors
Glutamate receptors are the key ion channels in the human brain responsible for synaptic signal transduction between the neurons. They are gated by ligands and voltage and upon opening release ions to the postsynaptic cell initiating further signaling cascades. Our group uses cryo electron microscopy and tomography to understand gating of glutamate receptors in mechanistic details in order to advance rational drug design. We aim at using single particle cryo-EM to obtain structures of isolated receptors at atomic resolution (3-4 Å). We further aim at obtaining structures of the receptors inserted into lipid vesicles at resolution of secondary structure (6-10 Å) in the defined functional states: with/without bound ligands and with/without voltage over the membrane.
Structure determination of receptors in vesicles is performed by sub-tomogram averaging from cryo electron tomograms. High resolution sub-tomogram averaging is a novel and challenging task. For this we complement our biochemical expertise with physicists and programmers and develop methods for better, faster and easier structure determination at higher resolution. We base software developments on our Matlab-based package Dynamo in which we also train other users and organize workshops.