Description du projet
Une vision moléculaire de la perception de la douleur
La douleur permet à notre corps de réagir face à des stimuli dangereux et s’avère essentielle à notre survie. Des récepteurs spécialisés, présents dans les neurones sensoriels innervant la peau et les organes internes, décodent des stimuli chimiques, thermiques et mécaniques. À leur tour, ces neurones transmettent les informations au système nerveux central. Le projet TransGeNo, financé par l’UE, entend combler le manque de connaissances sur ces récepteurs neuronaux qui reçoivent différents stimuli. À l’aide du criblage génomique par activation de transposons, des scientifiques prévoient d’introduire des mutations aléatoires dans les cellules pour déchiffrer le rôle de gènes spécifiques. Les résultats permettront d’identifier de nouvelles cibles prometteuses pour les traitements analgésiques et de contribuer aux futurs travaux de recherche sur la douleur.
Objectif
The perception of pain is crucial for our survival, enabling avoidance of harmful physical and chemical insults. Pain initiates in primary sensory neurons, which are highly variable cells innervating the skin, mucus membranes and internal organs. These neurons express combinations of receptor molecules decoding adverse mechanical, thermal and chemical stimuli. Receptor molecules sensitive to these cues decode such inputs into action potentials, which are then relayed to the central nervous system. Uncovering the identity and regulation of these sensory receptor molecules has long been of high interest to the neuroscience community. Being the first point of possible intervention in the signalling process that leads to the perception of pain, therapeutics designed to target these molecules have high promise. Many such receptors have been identified in the past decades. The thermo- and chemosensory TRP channels, intricately involved in our perception of inflammatory pain and injury-induced hypersensitivity, are at the focus of intensive investigations. The recently identified Piezo proteins have significantly advanced our understanding of how sensory nerves decode light touch and proprioception. Many receptors in this system, however, remain to be identified. Among them are mechanoreceptors of painful tactile stimuli, as well as those responsible for the tingling, numbing sensation induced by alkaloids found in Sichuan peppers. Identifying these would open new areas of pain research and provide new, promising targets for analgesic therapy. Here I will employ a new method, Transposon-Activated Genome-wide Screening (TAGS), to identify these receptors. Inspired by the process of evolution, TAGS creates random genetic mutations in vast cell populations and enlists the law of large numbers to identify the role of individual genes. In the long-term, I will broaden the scope of TAGS to enable gene discovery across multiple disciplines in biomedical sciences.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-RI - RI – Reintegration panelCoordinateur
LS2 9JT Leeds
Royaume-Uni