Project description
Visualising crystal formation in living cells
Biocrystallisation is the process by which living cells form crystals. When dysregulated, it contributes to human diseases such as kidney stones, gout and atherosclerosis. Understanding biocrystallisation is essential for developing therapies that inhibit crystal formation and prevent disease progression. However, current high-resolution imaging methods require samples to be frozen and therefore cannot capture these processes in real time. With the support of the Marie Skłodowska-Curie Actions programme, the LivEM project aims to overcome this barrier by developing the first liquid-phase electron microscopy workflow for imaging crystal formation in living cells. The proposed technology combines hardware and software advances, enabling the visualisation of biological processes at nanometre resolution. Project outcomes could transform and accelerate the development of therapies targeting crystal formation.
Objective
Biocrystallization, the process by which cells form crystals, contributes to inflammatory and pathogenic diseases such as atherosclerosis, kidney stones, and gout, and underpins malaria pathogenesis, where frontline therapeutics directly inhibit crystal formation. Understanding how cells create crystals is therefore vital for developing strategies to inhibit their formation and prevent disease progression. However, these dynamic crystal nucleation and growth processes in living cells, taking place at the nanometer scale, cannot be captured with current high-resolution imaging methods that rely on freezing samples. Liquid-phase electron microscopy (LP-EM) is a recently established tool for studying reactions in hydrated conditions at nanometer resolution, and it has been applied to investigate dynamic processes in inorganic, organic, and biological systems. Yet, imaging biological processes at high resolution remains beyond reach, primarily due to the loss of enzymatic activity under repeated exposure to damaging radiation. LivEM will address this challenge by integrating multiple dose- and damage-reduction strategies to establish the first live-cell LP-EM workflow. The project will entail (1) the design of graphene-based enclosures that provide radical scavenging, (2) optimization of sparse imaging to minimize scanned pixels, and (3) use of flow and recovery strategies to allow radiolytic relaxation. Together, these measures will reduce the effective dose by ~150–200×, enabling real-time nanoscale visualization of crystal formation without exceeding enzymatic inactivation thresholds. Guanine crystallization in unicellular eukaryotes will serve as a controllable model system for developing and validating the methodology. By bridging the gap between static high-resolution imaging and dynamic biological function, LivEM will open new opportunities for understanding clinically relevant biocrystallization and inform the development of drug therapeutics.
Fields of science (EuroSciVoc)
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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.
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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)
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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
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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
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(opens in new window) HORIZON-MSCA-2025-PF
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6525 GA Nijmegen
Netherlands
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