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Prof John Garthwaite
WIBR, Cruciform Building
Gower Street
London
WC1E 6BT
Appointment
  • Emeritus Professor of Experimental Neurscience
  • Wolfson Inst for Biomedical Research
  • Div of Medicine
  • Faculty of Medical Sciences
Research Themes
Research Summary
There are two main lines of research: (a), nitric oxide signalling in the brain, and (b), the pharmacology of voltage-gated sodium channels. (a). Nitric oxide signalling in the brain. Nitric oxide is a major transmitter in the central nervous system and, accordingly, is involved in a host of different functions, including learning and memory formation, feeding, sleeping, male and female reproductive behaviour, as well as in sensory and motor function. Some of these roles have been conserved through millions of years of evolution, in some cases dating back to animals with the most primitive nervous systems. Many clinical conditions (e.g. neurodegenerative and some psychiatric disorders) are also thought to involve aberrant nitric oxide transmission. The major part of our research is directed towards understanding how this signalling system operates in the brain at the cellular and molecular levels. There are several specific research projects, using a broad range of techniques (chiefly molecular biology, electrophysiology, immunocytochemistry and biochemistry), which can be categorised as follows: 1. Measuring nitric oxide signals. A major deficiency is a lack of understanding of the nature of nitric oxide signals in the brain, for example their amplitude and duration. We are developing new biosensors that offer unparalleled sensitivity and specificity for this purpose. 2. Molecular pharmacology of nitric oxide receptors. As with any transmitter, understanding how its receptors function is vital for decoding the language of communication. The receptor proteins designed to detect nitric oxide contain an intrinsic guanylyl cyclase catalytic domain and so generate cyclic GMP on stimulation. The receptors provide an astonishing degree of amplication of even brief (sub-second), low amplitude (sub-nanomolar) nitric oxide signals.
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