Contact Details

MRC Career Development Award Fellow,
Division of Structural Biology,
Henry Wellcome Building for Genomic Medicine,
Oxford, OX3 7BN, UK

Telephone: (+44) (0)1865 287564
E-mail: radu@strubi.ox.ac.uk

Research Areas

We aim to understand in molecular terms the 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 connectivity between nerve cells is crucial for information storage. Central nervous system neurons are connected by complex and dynamic supramolecular structures, termed synapses. Communication is typically achieved through activity-dependent release of small diffusible molecules, the neurotransmitters. In addition, there is increasing evidence for a direct physical contact between two neurons engaged in a synapse, through an intricate network of cell surface receptors, adhesion molecules, proteoglycans and secreted proteins that spans the ~20-25nm intercellular space. Little is known, however, about the higher order organization of molecules in this synaptic cleft, or indeed what might be the functional importance, in normal and pathological circumstances, of such supra-molecular arrangements. To date, technical limitations have hindered the study of such complex systems, despite their biological significance (cellular proteins generally never work "alone").

We currently focus on complexes assembled around, and modulating the function of, ionotropic receptors for glutamate and gamma-amino butyric acid (GABA), the two neurotransmitters that dominate signalling in the vertebrate central nervous system, as well as cell surface receptor enzymes (protein tyrosine phosphatases and kinases). Our work relies on structural biology techniques (X-ray crystallography, increasingly combined with cryo-electron microscopy/tomography) and complementary biophysical assays. Structurally-derived hypotheses are then validated in the relevant functional context, by live-cell fluorescence microscopy, electrophysiology and studies in model organisms.

By exploring trans-synaptic protein complexes of increasing size, we aim to reach a fundamentally different level of understanding of the molecular principles governing synaptic transmission. From a medical point of view, a wide spectrum of disorders including Alzheimer's, schizophrenia, Parkinson's and ischemic neuronal injury are linked to cell surface receptors responsible for synaptic plasticity. Dysfunction of the same molecular systems appears to be responsible for the cognitive decline linked to the 'normal' aging process or psychiatric conditions such as bipolar disorder and major clinical depression.