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Dr Ian Coombs is based in the department of Neuroscience, Physiology and Pharmacology (UCL Division of Biosciences).
Research summary
My research primarily focusses on AMPA receptors (AMPARs), a type of ligand-gated ion channel. AMPARs are located at junctions between neurons called synapses and are activated by the neurotransmitter glutamate to mediate the majority of fast-excitatory signalling in the brain.
In addition to this role in information transfer between neurons, AMPARs are crucial for both the initiation and the expression of synaptic plasticity, so are essential for memory formation. Alongside the AMPAR subunits themselves, native receptors are additionally comprised of a range of auxiliary subunits, which both direct receptor trafficking and finetune the electrical properties of the receptors.
I work closely with Professor Mark Farrant and Professor Stuart Cull-Candy in NPP, UCL, and a central part of our recent research has been to identify the diverse outcomes of auxiliary subunit association on AMPAR pharmacology. We use patch-clamp electrophysiology in combination with molecular approaches to investigate the properties of heterologously expressed recombinant receptors.
Using these approaches we have identified how key auxiliary subunits the TARPs and the cornichons influence multiple AMPAR properties including kinetics, channel conductance, and responses to both agonists and inhibitors, thus adding to our understanding of both neuronal excitation and how native receptors will respond to different classes of drugs.
Given their key role in brain signalling, deleterious genetic variations within the AMPAR genes GRIA1-4 disrupt normal synaptic transmission and plasticity. GRIA disorder patients display a range of neurological symptoms including seizures, intellectual disability (ID), and autism spectrum disorder (ASD). Many patients exhibit symptoms resistant to conventional therapies so there is an unmet need for new targeted treatments and much of my current research aims to tackle this shortfall. The overall aim of our ongoing research is to further dissect the mechanisms of glutamate receptor activity, focussing on their auxiliary subunits, to more fully understand their roles in both the physiology and pathology of the brain.
Education
Imperial College London
BSc, Biochemistry (1999)
Imperial College London
PhD, Electrophysiology (2003)
