Bevan Lab Research
Much of our current research involves studies on TRP Channels. TRP channels have diverse roles in sensory transduction and cellular regulation. We have a specific interest in TRP channels expressed by peripheral sensory neurons and interacting cells such as keratinocytes as well as non-neuronal cells in the gastro-intestinal tract.
Several of these channels are important sensors of thermal stimuli. For example, TRPV1 is activated by noxious high temperature (>42°C), TRPM8 by cool temperatures (<~28°C) and TRPV3 by warm temperatures (>32°C). TRPA1 can also be activated by noxious cold temperatures. TRPV1 and TRPA1 are expressed by sensory nerves that respond to noxious stimuli and these two channels are also sensitive to pungent chemicals such as capsaicin found in chilli peppers (TRPV1) and allyl isothiocyanate found in mustard and wasabi (TRPA1).
Our goal is to determine the roles of TRP channels and other ion channels and receptors in normal physiology and in disease states. The activities of channels and receptors are studied using electrophysiological measurements from native cells (such as sensory neurons) and cells heterologously expressing molecules of interest.
The ion channel TRPM8 is the physiological receptor for cold temperature, menthol and other agents that evoke a cooling sensation. The figure shows that a rapid cooling of the ambient solution evokes a large TRPM8 mediated current (control). Increasing concentrations of a TRPM8 antagonist blocks the cold activated current.
The behaviour of single cells to various stimuli is also investigated in microfluorimetry or multiwell plate assays using ion sensitive dyes to monitor changes in intracellular ion concentrations.
We also use RT-PCR and immunocytochemical approaches to reveal mechanisms that control the expression of key transduction molecules both in vitro and in vivo. Using these approaches we have identified some of the key endogenous mechanisms that activate and regulate TRP channels in sensory neurons. Our in vitro studies are complemented by behavioural experiments in animal models. Here we study the importance of different molecules and mediators by using pharmacological interventions and RNA interference as well as genetically modified mice.
Some of our recent studies have identified TRPM8 as a sensory neuron osmosensor whose activity is regulated by very small changes in extracellular osmolality. As a consequence TRPM8 plays an important role in regulating the rate of eye blinking in mice. A major focus of our current research is to determine the roles of TRPM3 in the normal functioning of peripheral sensory neurons and in chronic pain conditions.
We also collaborate with other laboratories in King’s, including the laboratories of Dr. David Andersson investigating mechanisms of sensory neuron transduction and of Professor Sue Brain exploring the roles of TRP channels in the vascular system.
Research in the Bevan Lab is supported by grants from the Wellcome Trust and the Medical Research Council.