Project description
Protein structure interactions in native cellular contexts with direct mass spectrometry
The cellular environment shapes protein structure and function, creating a diverse landscape of protein forms that is difficult to capture with conventional methods. The ERC-funded SystemDirectMS project develops direct mass spectrometry (direct-MS), an approach that preserves proteins in their native state within crude cell lysates, enabling the study of their interactions and diversity under near-physiological conditions. By extending this method from bacteria to human cells and tissues, and by establishing high-throughput and whole-organ analysis platforms, the project provides new tools to explore proteoforms and protein complexes. These advances enhance our ability to study proteins in biological context, with implications for cell biology, biotechnology and drug discovery.
Objective
Protein structure and consequently function is influenced by the cellular content. The array of splice variants, post-translational modifications, cleavages and the ability to bind cofactors and drugs, is governed by the surrounding cellular milieu. This is determined by internal and external cues such as cell type, developmental stage, stress conditions, disease and aging, which give rise to an ensemble of distinct protein entities. To study this diversity, there is a need for methods that enable structural studies under “close-to-life” conditions, maintaining the natural environment and biological diversity, features that are often lost during biochemical purifications.
Our recent discovery that native MS can be conducted within crude cellular lysates (direct-MS), while preserving the biological context, offers many new experimental avenues for investigating protein interactions and diversity. Here, we propose to take native MS to a new dimension: enabling a systemic view of cellular structure biology by endorsing technological, computational and methodological developments. To do this we will: (i) Establish a platform for high-throughput screening of protein interactions. (ii) Unravel protein interactions in human and other eukaryotic cells; (iii) Develop a method for whole-organ direct-MS analysis, unravelling the tissue-specific proteoform landscape. Each of our three independent but complementary aims involves a different biological system, going from bacteria through human cells to intact tissues. Together, these advances, in conjunction with the high-resolution and sensitivity afforded by current mass spectrometers, has the potential to advance a plethora of fields, including cell biology, pharmacology and biotechnology. Overall, we anticipate this project will promote the integration of direct-MS into the cellular structural biology toolkit, providing valuable insights not attained by other structural biology methods or artificial intelligence algorithms.
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 biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine pharmacology and pharmacy
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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)
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.
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-2022-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.
7610001 Rehovot
Israel
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.