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Transposon-activated Genome-wide search for novel Nociceptors

Project description

Molecular insight into pain perception

Pain allows our body to react to harmful stimuli and is central to our survival. Mechanical, thermal and chemical stimuli are decoded through specialised receptors present on sensory neurons innervating the skin and internal organs. In turn, these neurons relay the information to the central nervous system. The EU-funded TransGeNo project aims to close the knowledge gap on these neuronal receptors that receive the different stimuli. Using the method of transposon-activated genome-wide screening, scientists plan to introduce random mutations in cells to decipher the role of specific genes. The results will help identify new promising targets for analgesic therapy and fuel future efforts in pain research.

Objective

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.

Coordinator

UNIVERSITY OF LEEDS
Net EU contribution
€ 212 933,76
Address
WOODHOUSE LANE
LS2 9JT Leeds
United Kingdom

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Region
Yorkshire and the Humber West Yorkshire Leeds
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 212 933,76