Project description
Finding a new pathway for a comprehensive structural analysis of biological systems
For scientists to be able to understand and control biological processes, they need precise structural, conformational and chemical information on biological molecules. Different methods for the structural characterisation of folded proteins and protein complexes include cryo-electron microscopy (cryo-EM), native mass spectrometry (native MS) and preparative mass spectrometry (prep-MS). The EU-funded PNMS project intends to establish a new versatile pathway for a comprehensive structural analysis of biological systems by combining native MS, prep-MS and cryo-EM. This approach, called preparative native mass spectrometry, will involve designing ion optics to couple a mass-selected molecular ion beam from a commercial high-performance MS and a landing stage to add deposition capability. The project will enable a better understanding of structural variety, protein interactions and synthetic structures.
Objective
Precise structural, conformational, as well as chemical information of biological molecules forms the basis for comprehension and control of biological processes, including metabolism, pathological processes, and drug targeting. Cryo-electron microscopy (cryo-EM) has evolved into one of the leading methods for structural characterisation of folded proteins and protein complexes reaching atomic resolution through averaging. Thus, the unambiguous assignment of thousands of images to different oligomers, conformers, and fragments is a key requirement for high-resolution single particle cryo-EM. However, reliable preparation of homogeneous cryo samples remains one of, if not the, most important challenge in cryo-EM. Native mass spectrometry (native MS) allows to retain proteins in a near native state in an ultrapure gas-phase molecular ion-beam, providing complementary information on mass, composition, conformation and ligand binding sites. Preparative mass spectrometry (prep-MS) is able to generate ultrapure samples by soft landing of mass- and conformation selected molecules on surfaces for subsequent analysis. Here, we propose to implement preparative native mass spectrometry (pnMS), combining the strengths of native MS, prep-MS, and cryo-EM, to establish a new versatile pathway for comprehensive structural analysis of biological systems. We will design ion optics to couple a mass selected molecular ion beam from a commercial high-performance MS and a landing stage to add deposition capability. Initial experiments will focus on benchmark systems such as BSA and GroEL, before approaching more challenging proteins, including heat shock proteins (HSPs) and G-Protein coupled receptors (GPCRs). Ultimately, pnMS should enable the structural biology community to obtain a comprehensive understanding of structural variety (proteoforms), protein interactions (interactome), and synthetic structures, e.g. needed for customised medicine.
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 biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences molecular biology structural biology
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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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
OX1 2JD Oxford
United Kingdom
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.