David Wyllie

David Wyllie was appointed in 2011 to a Personal Chair in Ion Channel Physiology and Pharmacology. David is the Director of the Centre for Discovery Brain Sciences.

Neurons communicate with each other at specialised sites known as synapses. At these sites chemicals known as neurotransmitters are released from the presynaptic neuron and activate receptors located on the postsynaptic neuron, which generates a direct electrical signal and/or a biochemical signal. Dysfunction in neurotransmitter signalling can have profound and debilitating consequences for brain function.

This image shows excitatory cortical neurones derived from human pluripotent stem cells stained with DAPI – blue – a marker that binds to DNA found in the cell nucleus and MAP2b – seen in green – that identifies microtubule associated protein and which is enriched in the dendrites of neurones. Superimposed are examples of electrical currents recorded from a cortical neurone in response to increasing concentrations of GABA, the major inhibitory neurotransmitter in the brain, and the antagonism of these responses by picrotoxin, a drug which binds to and blocks GABA receptors.

My long-standing research interest is in ligand-gated ion channels (LGICs) — specialised pore-forming membrane proteins that are activated by neurotransmitters during ‘fast’ chemical synaptic transmission. In particular, my lab studies LGICs activated by L-glutamate — the major excitatory neurotransmitter in the mammalian brain.

Although glutamate activates several different classes of LGIC one in particular, the N-methyl-D-aspartate receptor (NMDAR) has been a major focus for our research. Through electrophysiological studies, my lab has contributed significantly to our understanding of the structure-function properties and physiological roles of the various subtypes of NMDARs.

NMDARs play pivotal roles in both normal and abnormal brain function. In early life for instance, they ensure that the correct wiring pattern is laid down in the developing brain. Furthermore, activation of NMDARs is required to learn certain tasks and store memories. However, both over and under-activation of NMDARs can be harmful for normal brain function.

A recent focus of our research is the electrophysiological and functional characterisation of defined neuronal and glial populations derived from human embryonic stem cells and induced pluripotent stem cells and specifically those from individuals suffering from neurodevelopmental and neurodegenerative diseases.

Our work seeks to assess the electrophysiological profile of such neurons in order to further our understanding of these debilitating diseases. Our overall aim is to develop an integrated approach to research that begins with the study of single protein molecules and synaptic function and extends, through collaboration with colleagues, to whole animal studies with an ultimate goal of the clinical study and treatment of disease.

Email: david.j.a.wyllie@ed.ac.uk

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