Grant: Discovery Grants Program - Individual

Our research group investigates neuro-immune interactions that modulate sensory neuron modalities (i.e. responses to mechanical, thermal and nociceptive stimuli). Ion channels expressed by distinct subsets of these neurons mediate many of these effects, and have recently been found to be directly and indirectly altered by the presence of immune factors including cytokines/chemokines, metalloproteases, and growth factors. In this new Discovery Grant submission, we will build on recent discoveries in my laboratory to investigate how chronobiological rhythms can regulate neuro-immune communication and alter somatosensory behaviour in vivo and sensory neuron activity in vitro. The over-arching goal of our research program is to identify novel mechanisms and intracellular signalling pathways that regulate neuronal activation/sensitization. While we commonly used injury models to explore these interactions, it has become increasingly clear that it is difficult to pinpoint specific targets of interest, due to the large number of candidates identified. A recent finding in my laboratory shows that thermal sensitivity to a radiant heat stimulus is absent during the dark phase in mice. This novel and exciting finding suggests that chronobiological rhythms can be used in healthy, uninjured animals to identify ligand-receptor interactions that may modulate these behavioural effects instead of having to rely injury/disease models. Other groups have shown that ion channels/receptors and immune mediators are modulated by circadian rhythms in the nave state. Therefore, we hypothesize that specific neuro-immune intracellular messaging pathways and receptor-ligand pairs are regulated by chronobiological rhythms to alter ion channel activity and somatosensory function. The specific Aims of this proposal are to:1. Characterize the circadian control of somatosensation, by focusing on external (light) and internal (molecular clock) cues [PhD1, MSc1, BSc1,2];2. Determine the cell type(s) contributing to chronobiological control of somatosensation [PhD1, Msc2, BSc3]; and3. Identifying the molecular cues altered by chronobiological rhythms to alter ion channel activity/function [PhD1, MSc3, Bsc4,5].Biological rhythms control various physiological processes in almost all animals; interactions between ion channels/receptors expressed by sensory neurons and secreted immune mediators alter behavioural activity across species. Thus, this study can impact the fields of neuroscience, immunology, and chronobiology by advancing our understanding of the interactions that occur between the three seemingly disparate systems. The research plan outlined here will also benefit Canada and Canadians by training graduate and undergraduate HQP in the collection, analysis and dissemination of data gathered using a diverse set of modern biological and biochemical techniques.