Neuronal circuits are fundamentally important for all aspects of animal physiology, from motion, vision and sensations to higher cognitive functions such as learning, memory, thought, speech and consciousness. The synapses – connecting points between neurons are continuously remodelled in response to novel experiences and hold the key to understanding how nervous systems work.
Little is known, however, about the fine structure of synapses. Increasingly long lists of molecular components are available, and we know how some of these look in atomic detail, typically in isolation. However, these players do not work alone. They must come together and coordinate to make a functional synapse.
We employ a combination of structural biology methods, including cryogenic electron microscopy and tomography, to define in high resolution the architecture of neurotransmitter receptors, their supramolecular assemblies and whole synapses. We then link structural work with neuronal physiology to provide fundamental mechanistic insights in neuroscience.
We apply structural knowledge to design novel molecular tools that help rebuild neuronal connections, modulate their function and repair damaged neuronal circuits. The majority of psychiatric and neurological disorders, from intellectual disability to Alzheimer’s disease, depression and addiction, as well as age-related cognitive decline and many debilitating injuries stem from impaired neuronal connectivity and errors in synaptic signalling. We help translate our discoveries to novel therapeutic approaches, in close collaboration with industry.