The Structural Biology of Memory

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We are interested in understanding the molecular mechanisms responsible for acquisition and storage of information in the brain, i.e. learning and memory. Research over the past five decades led to the idea that activity-dependent changes in the strength of synapses between nerve cells (synaptic plasticity) can represent a mechanism for information storage. The neurotransmitters glutamate and ?-amino-butyric acid (GABA) mediate most synaptic signalling in the vertebrate central nervous system. Their receptors play important roles in the induction, expression and/or modulation of synaptic plasticity. Dysfunction of these molecular systems appears to be responsible for the cognitive decline linked to the ‘normal‘ aging process. From a medical point of view, a wide spectrum of disorders including Alzheimer‘s, Parkinson‘s, schizophrenia, bipolar disorder, major clinical depression as well as ischemic neuronal injury are linked to the same receptor molecules.Our research is currently focused on the structural characterization of glutamate and GABA receptors, our main tool being X-ray crystallography. We aim to understand the molecular mechanisms governing their assembly, function and regulation, and to devise ways of modulating their signalling properties. This work is performed using cells grown in culture and state-of-the-art technology including robots for growing protein crystals and synchrotron-generated X-rays.