Control of body temperature: molecular basis of sensory and effector mechanisms

The molecular basis of how we sense ambient warm temperatures was unknown until recently. Our group showed that an ion channel called TRPM2, which spans nerve cell membranes and so regulates electrical activity in sensory neurons, directly senses warmth. We now want to use a similar method to elucidate the mechanism responsible for detecting extreme cold and the mechanisms by which thermosensitive neurons in the brain respond to warmth and maintain body temperature.

We will try to find out how we expend or conserve heat so as to maintain bodily temperature in the face of thermal challenges. Surprisingly, both the TRPM2 warmth-sensitive mechanism and the unknown cold-sensitive mechanism are present in sympathetic neurons, which are known to regulate body temperature, but the function of these novel sensory mechanisms is not known. We will also investigate how thermosensitive mechanisms in the brain are modulated to cause fever by looking at the effect of factors known to cause fever to see if these act on the same warmth-sensitive mechanisms we use to maintain normal body temperature, or whether there are  different mechanisms involved.

Discovering the molecular mechanisms involved in fever may aid the development of drugs to control pathological fever states.