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Molecular mechanisms of arenavirus cell entry and antibody-mediated neutralization

Objective

Over the last decades, multiple arenaviruses have emerged as zoonotic human pathogens. They cross the species barrier from their natural rodent hosts to humans and cause severe human disease. A key determinant of viral zoonotic transmission is the ability to bind the receptor molecules displayed on the surface of the host cell. Despite the threat these viruses cause to public health, little is known of how they infect the host and how they are targeted by the immune response. Furthermore, the treatment and prevention options are currently extremely limited.
Using techniques in structural biology, virology, immunology and cell biology, the proposed work aims at demonstrating the molecular mechanisms by which arenaviruses attach to human cells and are neutralized by the humoral immune response. First, crystallographic analysis of viral attachment glycoproteins alone and in complex with functional cellular receptors will be performed. Second, recombinantly derived viral glycoproteins will be used as immunogens for generation of specific monoclonal antibody libraries. The co-crystal structures of viral glycoproteins with cross-reactive, neutralizing antibodies, carefully selected using cell-based assays, will reveal the structural basis of antibody-mediated arenavirus neutralization. Therefore, by analogy to the development of antibody-based therapy against Ebola virus, the outlined multidisciplinary investigation will enable the rational design of antiviral reagents and vaccines.
The cross-disciplinary expertise, training and infrastructure available in the host and partner organizations will allow the Researcher to establish herself as a highly-skilled expert in molecular and structural virology. As an independent, multifaceted scientist, she will be able to make a tangible contribution to the development of novel antiviral therapies, thus improving the public health and economy and adding to science base both in Europe and worldwide.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Net EU contribution

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.

€ 183 454,80
Address
WELLINGTON SQUARE UNIVERSITY OFFICES
OX1 2JD Oxford
United Kingdom

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Region
South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 183 454,80
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