Objective
Cryo-electron microscopy has revolutionized the field of structural biology, primarily for macromolecular structure but also for cells and tissue sections—achieving resolutions at the limit of physical optics. While wide-field transmission EM (TEM) with phase contrast by defocus is the most commonly used modality in biology, the alternative, scanning transmission EM (STEM), has emerged as the mode of choice for atomic resolution in materials science. Seeking to endow biology with the benefits of STEM, our lab established STEM for cryo-tomography of biological cells and demonstrated its advantages for thick specimens and compositional contrast. We now seek to extend cryo-STEM to high-resolution, with an emphasis on tomography, by means of coherent detection (Obj1). This will be achieved by the method of integrated differential phase contrast (iDPC) using a segmented detector, from which we obtain simultaneously phase and depth contrast in a single scan.
The major expected benefits are: 1) minimization of image aberration, especially defocus with its associated complications for image interpretation, 2) reduction of beam-induced radiation damage by means of flexible scan and sampling patterns, and 3) improved reconstruction for tomography based on tailored data acquisition. We will validate the new methods for single particle analysis on standard macromolecular substrates and compare them to current state-of-the-art methods. Further, we will apply the new developments in 3D imaging to explore novel large-scale structures in chromatin we observed recently by whole-cell cryo-STEM tomography using current, low-resolution methods (Obj2). Labelling with halogenated nucleotides will reveal sites of active transcription or DNA synthesis.
The proposed approaches’ expected broad applicability and STEM’s unrealized potential for hardware simplicity should together ensure the wide adoption of cryo-STEM methods in biology, accelerated by our dissemination efforts (Obj3).
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 genetics DNA
- natural sciences physical sciences optics microscopy
- natural sciences biological sciences genetics nucleotides
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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)
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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 - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-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.