Descripción del proyecto
Información molecular sobre la percepción del dolor
El dolor permite que el cuerpo reaccione ante estímulos dañinos y es esencial para nuestra supervivencia. Los estímulos mecánicos, térmicos y químicos se descodifican a través de receptores especializados presentes en las neuronas sensoriales que inervan la piel y los órganos internos. Estas neuronas transmiten a su vez la información al sistema nervioso central. El proyecto financiado con fondos europeos TransGeNo tiene por objeto cerrar la brecha del conocimiento sobre estos receptores neuronales que reciben los distintos tipos de estímulos. Gracias al método de cribaje de todo el genoma activado por transposones, los científicos del proyecto planean introducir mutaciones aleatorias en células para descifrar el papel de determinados genes. Los resultados ayudarán a identificar nuevas dianas prometedoras para tratamientos analgésicos e impulsarán futuras investigaciones sobre el dolor.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-RI - RI – Reintegration panelCoordinador
LS2 9JT Leeds
Reino Unido