Project description
Atomic-resolution imaging of small biomolecules
Determining the 3D structure of biological molecules at atomic resolution is fundamental to understanding their function and designing effective therapies. Although cryo-electron microscopy has revolutionised structural biology, it remains unable to resolve small molecules below 50 kDa. With the support of the Marie Skłodowska-Curie Actions programme, the CryoBioPtycho project aims to address this through cryo-electron ptychography, an advanced imaging technique capable of reconstructing molecular structures with exceptional detail and clarity. Researchers will combine optimised imaging parameters with advanced computational reconstruction algorithms to unlock structural insights into previously inaccessible targets. The generated platform is expected to have broad implications for drug design and biotechnology.
Objective
This project aims to establish an automated cryo-electron ptychography (cryo-EP) workflow to achieve atomic-resolution (better than 4 Å) structural determination of biological macromolecules, including those under 50 kDa, which remain beyond the reach of conventional cryo-electron microscopy (cryo-EM). Cryo-EP offers superior contrast transfer and defocus tolerance compared to mainstream cryo-EM and cryo-integrated differential phase contrast (cryo-iDPC), yet its application in structural biology is hindered by challenges such as low-dose data acquisition, probe position inaccuracies, motion blur, and lack of integrated software.
To address these limitations, we propose a multidisciplinary approach combining optimized electron-optical parameters, dose-fractionated acquisition, multi-convergence semi-angle (multi-CSA) imaging, and robust computational reconstruction algorithms. The project will develop an automated, open-source software pipeline for data acquisition and processing, leveraging state-of-the-art cryo-electron microscopes (e.g. Titan Krios G4, BIOTOOL system operating at liquid helium temperature), high-speed detectors (e.g. Dectris Arina, TimePix) and high-performance computing resources. Validation will be performed on benchmark samples (e.g. TMV, apoferritin) and extended to challenging targets such as hemoglobin (60 kDa) and fetuin A (40 kDa).
By overcoming current technical barriers, this project will enable high-resolution structural insights into previously inaccessible biomolecules, with broad implications for drug design, biotechnology, and fundamental biology. The outcomes will be disseminated through open-access publications, software releases, and public engagement, ensuring wide adoption and sustainability within the structural biology 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 chemical sciences inorganic chemistry noble gases
- medical and health sciences basic medicine medicinal chemistry
- natural sciences biological sciences biochemistry biomolecules
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences molecular biology structural biology
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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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2025-PF
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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.
52428 JULICH
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.