Project description
Decoding GPCR signalling at the single-molecule level
G protein-coupled receptor (GPCR) signalling is central to human health, yet its molecular logic remains poorly understood. The ERC-funded SignAlloMod project aims to close this gap by developing a novel single-molecule approach to quantitatively decode key allosteric phenomena in GPCR signalling, including ligand efficacy, biased signalling and allosteric modulation. By establishing a workflow that integrates biophysics, microfluidics and quantitative modelling, SignAlloMod will create an experimental framework for studying GPCRs at the single-molecule level. The project will investigate three model receptors, enabling the separation of ligand- and transducer-specific effects. Expected outcomes include a validated platform for measuring GPCR binding and conformational dynamics, the generation of quantitative ligand profiles and the development of new principles for designing pathway-selective drugs guided by physical models.
Objective
G protein-coupled receptors (GPCRs) are key to human physiology and disease, yet their signaling remains enigmatic. What we do know is that GPCRs signal by means of allosteric communication across the cell membrane, acting as logic gates that relay signals from extracellular ligands to various intracellular transducers. Nonetheless, the logic underlying GPCR signaling at the molecular level is not yet understood. This is particularly true of three key signaling phenomena: ligand efficacy, biased signaling, and allosteric modulation. In SignAlloMod, we will address this challenge and investigate the logic of transmembrane signaling through GPCRs at the single-molecule level. We will develop a new single-molecule microfluidic method that enables simultaneous measurement of transducer binding and receptor activation states, making rigorous, quantitative models of GPCR allostery experimentally accessible. This will allow us to separate, for the first time, ligand-specific from transducer-specific effects in GPCR signaling, ultimately enabling us to decode the molecular logic of GPCR signaling. We will use prototypical GPCRs to establish our approach and to study ligand efficacy, biased signaling, and allosteric modulation. The quantitative insights into ligand-specific and transducer-specific effects afforded by SignAlloMod will redefine our understanding of GPCR signaling. SignAlloMod will provide pharmacological ligand profiles with unprecedented detail, opening new horizons for drug discovery and pharmacological intervention guided by physical principles.
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)
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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-2024-STG
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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.
8010 GRAZ
Austria
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.