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UCL Institute of Mental Health

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Prof Trevor Smart

Prof Trevor Smart

Schild Professor of Pharmacology

Neuro, Physiology & Pharmacology

Div of Biosciences

Joined UCL
1st Apr 2002

Research summary

Controlling the innate excitability of neurons is vital for a healthy nervous system. There are various ways of achieving this aim, but by far the most important involves the inhibitory transmitter, GABA. Fast synaptic inhibition is achieved by rapid activation of GABA-A receptors whilst longer term modulatory effects on excitability are accomplished by GABA-B receptor activation. It is increasingly clear that there are many different isoforms of GABA-A receptors and these appear, in particular examples, to be targeted to discrete areas of the brain, and within single neurones, to discrete inhibitory synapses. Given the critical role(s) these receptors play in neuronal function, they form a logical target for therapeutic agents to ameliorate uncontrolled neuronal excitability, in addition to being involved in numerous neurological disorders, such as epilepsy and anxiety. Our research in neuroscience at UCL is supported by long-term programme grant funding from the Medical Research Council and the Wellcome Trust. We use multidisciplinary integrated approaches, based on electrophysiology, cell and molecular biology, imaging and neurogenetics, to elucidate the molecular and network properties of GABA receptors. These techniques, for network, whole-cell synaptic and single channel studies, are used in native neurones coupled with optical and genetic adaptations to modify the response profile of GABA-A receptors. To gain proof-of-principle for our manipulations of GABA-A receptor structure-function, we employ numerous DNA or RNA tranfection methods (allowing receptor expression in cells following viral infection, direct microinjection and lipofection). In addition, we are also using imaging/optical techniques, with various fluorophores and photoactivated caged compounds, to enable the tracking in live cells of receptor subunits in real time into and out of inhibitory synapses. At the synaptic and network levels, similar approaches are used to study the physiological control of inhibitory transmission and synaptic plasticity by retrograde and autocrine messengers. This also includes how other endogenous regulators in the nervous system (e.g., phosphorylation and neurosteroids) can modulate the function of specific GABA-A receptors at specific inhibitory synapses to affect network behaviour. Overall, our major objective is to provide a complete molecular description of the therapeutically important GABA receptor classes that will enable a deeper understanding of their role in neuronal networks in both healthy and diseased states.

Teaching summary

Trevor Smart delivers key introductory lectures to Pharmacology, Neuroscience and Medical undergraduate students. 

 - He lectures to first year students on the nervous system and drugs

- He delivers lectures on Anxiety and Depression to second year science and medical students

- To third and fourth years students, he provides lectures on Epilepsy and the basis for inhibitory neurotransmission involving the GABA-A receptor

- Practical demonstrations of frontline research techniques in electrophysiology are delivered in his laboratory each year.

- He also runs a series of Medical tutorials on pharmacology and therapeutics

- Postgraduate education is delivered via PhD doctoral training programmes

Education

University of London
Doctorate, Doctor of Philosophy | 1983
School of Pharmacy, University of London
First Degree, Bachelor of Pharmacy | 1977

Biography

Trevor Smart graduated with a First Class B. Pharm honours degree and joined the NHS before completing a PhD in Pharmacology from the University of London. After postdoctoral research in Switzerland (Sandoz) and the USA (Baltimore), and a Wellcome Trust Research Fellowship, he eventually became the Wellcome Professor of Pharmacology at the School of Pharmacy, prior to his move in 2002 to University College London.

 

His work has centred on the molecular pharmacology and physiology of the GABAA receptor which is the major inhibitory neurotransmitter receptor in the brain pivotally involved in controlling nerve cell excitability. It is a target for several therapeutic classes of drugs and features prominently in neurological diseases.

 

By adopting a multidisciplinary approach, his work has centred on understanding how endogenous regulators in the nervous system can modulate the function of GABA receptors and inhibitory synapses. This work has been responsible for numerous seminal discoveries regarding the receptor’s structure-function properties, revealing where both therapeutic and endogenous ligands can bind to these receptors and how they can affect receptor function in a subtype-selective manner. Moreover, intracellular regulation of GABA receptors by anchoring and trafficking proteins and following modification of receptor structure by phosphorylation have enabled a detailed, dynamic profile of this receptor to be assembled. These studies have all impacted on the mechanisms involved in GABA receptor targeting to synapses and their short- and longer-term regulation of function at synapses (plasticity) in both healthy and diseased states.

 

He has previously been awarded the Sandoz prize for Pharmacology from the British Pharmacological Society, the Lilly Award for Pharmaceutical Sciences and the RPSGB Conference Science Medal. He became an FRPharmS in 2000, FBPharmacolS in 2004 and FMedSci in 2006. He delivered the 2009 Distinguished Goudey Lecture in Pharmacology in North America, and in Dec 2012 delivered the prestigious biennial Gaddum Memorial Lecture (Award) to the British Pharmacological Society

 

He holds the Schild Chair in Pharmacology and is the Head of the Research Department of Neuroscience, Physiology & Pharmacology at UCL. He is also the Chair for UCL’s Neuroscience Research Domain covering over 500 fundamental and clinical neuroscience investigators.

 

 

 

Publications