Objective
Fusion of two biological membranes is essential to life. It is required during organism development, for trafficking of material between cellular compartments, for transfer of information across synapses, and for entry of viruses into cells. Fusion must be carefully controlled and the core fusion components are typically found within a complex regulatory machine. There have been decades of research on the structure and function of individual components, on the dynamics and biophysics of fusion, and on phenotypes resulting from mutating or inhibiting component proteins. These have led to a model for fusion in which regulated refolding or assembly of proteins draws two membranes closer together until they fuse. Despite this breadth of study, we know very little about how the components of the fusion machinery function in context: How are they arranged on the membrane around the site of fusion? How do they respond structurally to regulation? How does the fully assembled machinery rearrange to reshape the membrane and drive fusion? These gaps in knowledge can be attributed to a shortage of structural biology methods able to derive structural data on proteins assembled within complex, heterogeneous or dynamic environments such as a fusion site. Here I propose to apply a combination of state-of-the-art cryo-electron tomography, image processing and correlative fluorescence and electron microscopy methods to obtain detailed structural information on assembled fusion machineries and of fusion intermediates both in vitro and in vivo. I will study how influenza virus fuses with a target membrane, complemented by studies on fusion of HIV-1 and of synaptic vesicles. By determining how viral and synaptic fusion complexes reposition and restructure prior to fusion, how they arrange around the fusion site, how they reshape the membrane to induce fusion, and how these processes can be regulated and inhibited, I will derive a mechanistic model of membrane fusion in situ.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences microbiology virology
- medical and health sciences health sciences infectious diseases RNA viruses ebola
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences molecular biology structural biology
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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.
ERC-COG - Consolidator Grant
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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-2014-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.
SN2 1FL SWINDON
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.