Project description
A disruptive technology for studying single-protein interactions
Key cellular processes as well as cell-to-cell interaction commence with protein interaction on the plasma membrane. Although membrane proteins constitute the majority of current therapeutic targets against various diseases, their nanoscale organisation has not been fully characterised. The EU-funded ReceptorPAINT project aims to address existing technical challenges by developing a disruptive method to study the spatial distribution of single proteins on the cell surface. Researchers will use DNA paints to light up proteins that reside 1 nm apart and investigate their interaction, focusing on immune and tumour cells. Results will provide fundamental knowledge on the mechanism of anti-tumour immunity and pave the way for more efficient immunotherapies.
Objective
Targeting cell surface proteins to alter cellular behavior is a major aim of many therapeutics. Recently approved immunotherapeutic drugs trigger anti-tumor immunity by disrupting key cell surface proteins that guide immune cell interactions. Despite the cell surface representing a major site of drug action, its nanoscale organization remains poorly characterized. The main reason for this is largely due to technical limitations of current fluorescence and super-resolution imaging approaches, which do not allow high-throughput measurements of the spatial localization and interaction of hundreds of proteins with true single-protein- resolution on cell surfaces. We here propose to develop exactly such a disruptive capability by advancing recently developed DNA-PAINT microscopy to enable the visualization and quantification of all relevant cell surface proteins at single-protein-resolution. We will achieve this by innovating DNA-PAINT to enable isotropic 1-nm-resolution, develop DNA-based protein binders against all cell surface proteins, and devise multiplexing capabilities to resolve them with single-protein-resolution over large fields of view, reaching the ultimate goal of enabling Imaging Receptomics. We will then apply this to test the central hypothesis that surface protein architecture and patterning on immune and tumor cells dictates the outcome of their interactions. We will map the nanoscale organization of hundreds of key immunomodulatory surface proteins and their corresponding ligands on key interacting pairs of immune cells relevant to current immunotherapy approaches (dendritic cells and T cells), as well as tumor cells. This will yield fundamental insights into the molecular architecture of their interactions and potentially enable the future development of more refined “pattern”-based immunotherapeutics. Collectively, this highly multidisciplinary and novel approach has the potential to be ground-breaking across a range of research fields.
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.
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology immunotherapy
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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.
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.
ERC-COG - Consolidator Grant
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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-2020-COG
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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.
80539 Planegg
Germany
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.