Objective
Structural biology provides insights into protein function but generally requires purified complexes, which necessitates removing the protein from its native context. We therefore lose in situ information. Cryo-electron tomography (cryoET) provides this information, but finding a specific protein in a cell is akin to searching for a needle in a haystack 50 m tall. We are at the forefront of developing a technique to solve this problem; by combining super-resolution (SR) light microscopy on samples prepared for cryoET we can locate specific proteins and events within whole mammalian cells. This information can be correlated with 3D cryoET volumes to perform in situ structural biology. We call this technique super-resolution cryo-correlative light and electron microscopy (SRcryoCLEM). Here, I describe how we will enhance SRcryoCLEM and use it to image antibody-activated aspects of human immunity, enabling the development of cutting-edge immunotherapeutics.
The first aim of this proposal is to augment SRcryoCLEM with multicolour imaging and automated data analysis. Spectrally-distinct fluorescent proteins will be identified that are ideal for cryoSR imaging, and AI-based volume segmentation and automated particle picking will help to democratise in situ structural biology.
The second aim is to deliver in situ structural data to explain discrepancies in antibody effector functions with an unknown structural cause, which will be used to perform structure guided antibody design to further enhance their effector functions for the benefit of human health.
The third aim is to discover the structural determinants orchestrating antibody-mediated phagocytosis by macrophages using SRcryoCLEM. This immunologically-pivotal mechanism is poorly understood, but is being exploited as a next-generation therapeutic. Our data will provide crucial insights into the fundamental biological processes underlying macrophage function, allowing therapeutic gain.
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 physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
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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
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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-ERC - HORIZON ERC 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-2024-COG
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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.
BS8 1QU BRISTOL
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.