Objective
The fusion of biological membranes underlies basic cellular processes of vesicle transport as well as the infectivity of enveloped viruses. The haemagglutinin (HA) glycoprotein of influenza viruses mediates fusion between viral and cellular membranes at the pH of the endosome to deliver the viral genome into the cytosol. Despite its high surface variability, its fusion machinery is conserved among HA subtypes and is a prime target for broadly neutralizing antibodies. HA consists of the receptor-binding HA1 and the fusion-mediating HA2, which has two membrane-interacting elements: the N-terminal fusion peptide and a C-terminal transmembrane anchor. At low pH, HA2 undergoes a series of conformational changes that project the fusion peptide out of a protein pocket towards the target membrane, and subsequently bring fusion peptide and transmembrane anchor, and likely the two membranes, into close proximity. The conformational changes are defined by crystal structures at neutral and low pH, but the membrane-associated parts of the protein were absent from the crystallization constructs. To define their roles and interactions, I propose to solve the full-length structures of HA at neutral pH and of HA2 at low pH by x-ray crystallography using state-of-the art crystallisation methods. High amounts of detergent solubilized membrane protein can already be purified from virus. The crystallization process will be aided by biophysical protein characterization and electron microscopy. The structures will impact our understanding of the mechanism of membrane fusion and help develop broadly neutralizing antibodies as influenza therapeutics. The project will complement my previous training in the structural biology of soluble proteins to membrane protein specific methods, electron microscopy and virological assays.
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 earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics genomes viral genomes
- natural sciences physical sciences optics microscopy electron microscopy
- medical and health sciences health sciences infectious diseases RNA viruses influenza
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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.
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.
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.
FP7-PEOPLE-2013-IEF
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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.
Coordinator
NW1 1AT London
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.