Pain is a major medical concern and there is an undeniable need to improve the therapeutic options in pain management. In this project, a simple model organism is used to identify and characterize new potential drug targets.
Nociception is defined as the neural processes of encoding and processing noxious stimuli triggering pain. Nociception and temperature sensation are related processes. The general goal of this research project is to shed new light on their molecular and neural basis, by using the small nematode Caenorhabditis elegans. This model organism presents several advantages, including the availability of a complete nervous system wiring diagram, efficient genetic techniques, and a stereotyped avoidance behaviour in response to noxious heat, providing a simple readout of thermal nociception. Recent work by the applicant has demonstrated the suitability of this model. New assays were developed to quantify the heat avoidance behaviour and a pilot mutagenesis screen led to the identification of several genes, which mutation impairs noxious heat avoidance. The specific goals pursued in the present project are:
1) to characterize the interplay between the recently discovered “heat avoidance” genes
2) to identify more genes required for heat avoidance, by scaling up the genetic screen
3) to identify the neurons involved, by using cell-specific gene rescue in mutants and by neuronal ablation
4) to understand the logic of the neural circuit involved by expressing light-activated channels enabling an on-demand artificial neural activation
Because thermal nociception mechanisms appear to be at least partially conserved between worms and humans, characterizing the genetic and neural pathways involved will provide novel insights on potential therapeutic target for pain management.
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