Project description
New therapeutic targets for pain-related disorders
Pain protects people from harm but some people never feel it. Nociceptors are the sensory neurons that detect sustained, potentially damaging force. Scientists have long thought that nociceptors do this via mechanically activated ion channels in their membranes. However, Schwann cells at the site likely also participate. Identifying molecules involved in this secondary ‘apparatus’ for pain detection opens the door to new treatments for pain-related conditions that currently lack adequate therapies. The ERC-funded Pain Channels project aims to achieve this by using ultra-low-input spatial proteomics, BioID (a screen for protein-protein interactions), high-throughput electrophysiological screening, and novel genetic strategies.
Objective
Pain results from activation of the nociceptive sensory system, which is built upon the primary afferent nociceptor a type of sensory neuron specialized to detect, code and relay information about potentially or actually damaging stimuli. Humans lacking properly functioning nociceptors never experience pain and have reduced life expectancy and suffer severe disability. Nociceptors detect sustained force into ranges that are potentially damaging and sustained nociceptor activation will always lead to pain. It has been assumed that mechanical force transduced by nociceptors requires mechanically activated ion channels in the nociceptor membrane. However, recent data suggests that sensory Schwann cells that wrap the nociceptor ending also participate in force transduction. The aim of this proposal is to identify molecules specifically involved in nociceptor force transduction at this neuroglial site. We have already identified an ion channel (Tmem87a/ELKIN1) and an extracellular tether protein (TENM4) as being involved in nociceptor force transduction. In addition, STOML3 modulates ELKIN1 function and can sensitize almost all nociceptors to mechanical force. The identification of a set of molecules involved in force transduction (ELKIN1/TENM4/STOML3) will allow us to design “guilt by association” approaches to identify new players. We will use ultra-low input spatial proteomics, BioID and high throughput electrophysiological screening to achieve this aim. We have designed novel genetic strategies to interrogate the function of candidate proteins in nociceptor force transduction with timescales ranging from weeks to minutes. This ambitious and challenging project promises to deliver novel molecular targets that can be used to specifically target nociceptor force transduction. Specific targeting of nociceptor force transduction could be a powerful new way to treat multiple pain types poorly served by existing therapies.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2023-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
13125 Berlin
Germany
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