Staff Profile

My principal research interests focus on the regulation of synaptic connectivity in health and disease. Efficient synaptic communication is fundamental for every brain process. Dynamic structural and functional changes at the synapse are essential for the formation and refinement of neuronal networks. Importantly, mutations in genes linked to synapse formation and maintenance are associated with diseases of neurodevelopmental origin including epilepsy and autism spectrum disorders (ASD). Consequently, it is essential to understand the mechanisms that modulate the growth and maintenance of synapses in the healthy and diseased brain.

Using a multidisciplinary approach combining cellular biology, live imaging, and electrophysiology techniques in rodent models, I have established how a major class of synaptic modulators, Wnt secreted proteins, function at the synapse and respond to neuronal activity in the developing and mature nervous system. My research has been fundamental in establishing how Wnts contribute to synaptic plasticity and synapse integrity. However, not all findings in rodent model systems can be directly translatable to humans. Therefore, it is crucial to develop and use alternative approaches which can address these fundamental differences. I have established an optimised system which preserves developing and mature human cortical tissue in culture for days to weeks. Utilising this in vitro translational technique, I now aim to study how dysfunction in pre- and postsynaptic proteins cause epilepsy and ASD in humans. This current work is also funded by CANDO ("Controlling Abnormal Network Dynamics with Optogenetics", see http://www.cando.ac.uk/), a project aiming to develop a cortical implant for optogenetic neural control of focal epilepsy.

• Mcleod F, Dimtsi A, Marshall AC, Lewis-Smith DJ, Thomas R, Clowry GJ, Trevelyan AJ. Altered synaptic connectivity in an in vitro human model of STXBP1 encephalopathy. Brain 2022, Epub ahead of print.