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FUSION SIGNED

Single Molecule Imaging-based design of HIV-1 vaccines

Total Cost €

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EC-Contrib. €

0

Partnership

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 FUSION project word cloud

Explore the words cloud of the FUSION project. It provides you a very rough idea of what is the project "FUSION" about.

microscopy    combinations    systematically    single    molecule    functional    co    nanometre    virus    insights    light    class    particles    perturb    cells    identification    block    smlm    stoichiometry    surface    combining    world    last    neutralizing    fusion    cxcr4    tracking    drugs    deeper    visualized    hiv    edge    reaction    bnabs    putative    readouts    few    fluctuation    group    resolved    time    recognition    decipher    discovered    absence    aid    vaccine    conserved    living    action    antibodies    transmission    circulating    technologies    experiments    macrophages    interactions    avenues    characterizing    applies    host    families    oligomeric    env    neutralize    cutting    cd4    strains    receptor    fluorescence    laboratory    radically    hope    cell    standard    simultaneously    mechanism    receptors    precise    ascertain    mechanistic    multiplex    3d    emerged    re    gold    unveil    rational    quantified    spectroscopy    polyclonal    molecular    ccr5    dimensional    big    antibody    desig    mode    tropism    localization    disrupt    drug    imaging   

Project "FUSION" data sheet

The following table provides information about the project.

Coordinator
KING'S COLLEGE LONDON 

Organization address
address: STRAND
city: LONDON
postcode: WC2R 2LS
website: www.kcl.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 2˙280˙390 €
 EC max contribution 2˙280˙390 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-COG
 Funding Scheme ERC-COG
 Starting year 2020
 Duration (year-month-day) from 2020-04-01   to  2025-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KING'S COLLEGE LONDON UK (LONDON) coordinator 2˙280˙390.00

Map

 Project objective

The HIV-1 vaccine research has re-emerged in the last few years due to the identification of antibodies that neutralize most HIV-1 circulating strains. A deeper understanding of the mechanistic mode of target recognition for these antibodies represents a big hope in the field. This project aims at understanding and characterizing polyclonal antibody responses to aid rational vaccine design via radically new technologies on light microscopy. The molecular mechanism of time-resolved HIV-1 fusion will be visualized and quantified on the surface of living cells by combining real-time single virus tracking, fluorescence fluctuation spectroscopy and 3D single molecule localization microscopy (SMLM) imaging. The implementation of a new technology that allows three-dimensional nanometre localization of single particles will allow us to multiplex single molecule experiments with functional readouts for single-virus HIV-1 fusion simultaneously. Here, I will systematically establish the mechanism of action of different families of neutralizing antibodies and how they disrupt the three-step HIV fusion reaction, conserved among different HIV tropism, recently discovered by our group. I will unveil the molecular insights on the precise Env-induced, time-resolved stoichiometry of CD4 and co-receptors (CCR5 or CXCR4) in the presence and absence of different combinations of bNAbs and study their impact on HIV transmission. FUSION will open new avenues to design putative drugs that target host-specific receptor and co-receptor oligomeric states to block HIV-1 fusion. This project systematically applies cutting-edge time-resolved imaging approaches as a gold standard to ascertain how different combinations of bNAbs perturb the HIV fusion mechanism in CD4 T cells and macrophages. I will establish a world-class laboratory in HIV-1 and single molecule microscopy. I will decipher several key virus–host cell interactions at molecular level and contribute to rational vaccine and drug desig

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