Project description
Elusive protein structures with time-resolved cryo-EM
Understanding transient protein structures is vital for biology, drug development, and biotechnology. Electron cryogenic microscopy (cryo-EM) has revolutionised protein structure determination, but many fleeting protein states remain out of reach. Time-resolved cryo-EM (trEM) offers a solution, though its widespread use has been hindered by technical challenges. A new ERC-funded project aims to overcome these barriers by refining trEM sample preparation, testing a wide range of protein samples, and developing a compact, pre-industrial prototype. These advancements will enhance the method’s reliability, making it more accessible to cryo-EM researchers and commercial companies alike, unlocking new possibilities for the study of dynamic protein interactions.
Objective
Knowledge of protein structure is fundamental for the understanding of biology, disease mechanisms, drug development, and biotechnology. Recent progress with electron cryogenic microscopy (cryo-EM) simplified and tremendously accelerated the determination of protein structures including multiple protein conformations. Many functionally important protein conformations and protein-protein complexes are transient and are not easily accessible by conventional cryo-EM. These transient states can, however, be freeze-trapped and their structures solved to high resolution using the time-resolved cryo-EM (trEM). Despite its long history and high interest from the cryo-EM community, technical difficulties prevented the spread of the methodology, and no commercial devices enabling trEM sample preparation exists. During the ERC-CoG project, we developed a new approach to the preparation of trEM samples which has advantages over the other reported technologies. In this POC project, we propose to undertake steps that will explore the suitability of our technology for application to a wide variety of protein samples and to evaluate the commercial potential of the technology with aim of bringing it to cryo-EM users rapidly. To achieve this, we plan to (1) expand the number of protein samples to be tested on our instrument thus enabling rapid user access and simultaneous validation of the methodology, (2) perform additional research to further improve the method by addressing the remaining bottlenecks, (3) make steps towards defining the best process and materials for industrial production of microfluidic chips, and (4) redesign the time-resolved plunger into a compact pre-industrial prototype. These steps will broadly validate, improve, and derisk the technology to make it more attractive to cryo-EM instrumentation-making companies to bring the technology to the cryo-EM community.
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
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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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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-POC - HORIZON ERC Proof of Concept 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-POC
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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.
9052 ZWIJNAARDE - GENT
Belgium
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