Project description
Molecular insight into brain function
The central nervous system mediates signal transmission at synapses through glutamate receptors, which can be found on both neuronal and non-neuronal cells. These receptors are involved in regulating a wide range of processes throughout the brain, spinal cord, retina, and peripheral nervous system. It is believed that glutamate receptors may have significant implications for various neurological disorders. The EU-funded gluactive project aims to dissect the mechanisms of temporal and spatial activation of glutamate receptors through the binding of the neurotransmitter glutamate. The project will improve our understanding of how the brain works at the molecular level in health and disease.
Objective
Glutamate receptors are amongst the most important signalling molecules in the brain. Activation of receptors by the neurotransmitter glutamate is required for nervous system function, underlying cognition, learning, memory and sensation. Despite advances in the study of their structural biology and physiology, how glutamate receptor complexes are activated remains unclear. With this proposal, we aim to determine how receptor activation and desensitisation are driven by glutamate binding. Our central approach is to map the motions of glutamate receptors during synaptic-like activity, in order to grab the frames needed to produce the movie of receptor activation. We aim to detect motion within the receptor on the angstrom scale by trapping conformational states during activation with artificial metal ion binding sites and disulfide bonds. Trapped receptors will be examined using biochemical measures of subunit association, biophysical reports of receptor activity and by structural biology. The results we obtain will be useful to rationally interfere with excitatory synapses in the brain and may therefore help the development of therapies.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
12489 Berlin
Germany