Descrizione del progetto
Informazioni molecolari sulla percezione del dolore
Il dolore consente al nostro corpo di reagire agli stimoli dannosi ed è fondamentale per la nostra sopravvivenza. Gli stimoli meccanici, termici e chimici vengono decodificati attraverso recettori specializzati presenti sui neuroni sensoriali che innervano la pelle e gli organi interni. A loro volta, questi neuroni trasmettono le informazioni al sistema nervoso centrale. Il progetto TransGeNo, finanziato dall’UE, mira a colmare il divario di conoscenza su questi recettori neuronali che ricevono i diversi stimoli. Utilizzando il metodo di screening dell’intero genoma attivato da trasposoni, gli scienziati hanno in programma di introdurre mutazioni casuali nelle cellule per decifrare il ruolo di geni specifici. I risultati contribuiranno a identificare nuovi promettenti obiettivi per la terapia analgesica e alimenteranno gli sforzi futuri nella ricerca sul dolore.
Obiettivo
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.
Campo scientifico
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Meccanismo di finanziamento
MSCA-IF-EF-RI - RI – Reintegration panelCoordinatore
LS2 9JT Leeds
Regno Unito