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DesignerAntibiotics

Towards the prevention of aminoglycoside antibiotic-related deafness

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 DesignerAntibiotics project word cloud

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25    investigation    treatment    antibacterial    100    structural    first    impairment    university    22    resistant    incidence    care    human    economically    imperial    safer    drug    drawback    maintaining    damage    billion    profoundly    effect    antimicrobials    potency    modify    infections    critically    murine    masters    data    chemically    bacteria    aminoglycosides    biobank    molecular    aminoglycoside    ucl    resistance    hearing    occurs    compounds    neonatal    crystallography    children    college    class    distinction    limits    amounts    gt    language    annual    exposed    antibiotics    incurred    group    78    20    candidate    profound    stanford    rare    life    diminish    patient    urgent    1555a    clinical    annually    inner    impedes    acquisition    infancy    patients    mutation    london    patented    threatening    suffer    caused    journal    guided    deaf    despite    publication    intensive    cells    shown    15    biology    irreversible    die    million    dna    phd    genetics    generation    ear    vitro    mitochondrial    published    ototoxicity    models    author   

Project "DesignerAntibiotics" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY COLLEGE LONDON 

Organization address
address: GOWER STREET
city: LONDON
postcode: WC1E 6BT
website: n.a.

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 251˙857 €
 EC max contribution 251˙857 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-GF
 Starting year 2017
 Duration (year-month-day) from 2017-02-13   to  2020-02-12

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON UK (LONDON) coordinator 251˙857.00
2    BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY US (STANFORD) partner 0.00

Map

 Project objective

Aminoglycosides are critically important antimicrobials used in the treatment of life-threatening infections. A major drawback of usage is hearing loss caused by irreversible damage to the inner ear (ototoxicity). Ototoxicity occurs in ~20% of patients and ~100% of patients with the m.1555A>G mitochondrial DNA mutation. The largest EU patient group exposed to aminoglycosides are children in neonatal intensive care and the effect of hearing loss during infancy is particularly profound as it impedes language acquisition. Thus, there is an urgent need to develop safer aminoglycoside antibiotics. Ototoxicity limits usage despite the antibacterial potency and low incidence of drug resistance provided by this class of antibiotics. Economically, the annual EU cost incurred by drug resistant infections amounts to €1.5 billion, and the cost of hearing impairment is estimated to be €78 billion. Moreover, 25,000 EU patients die annually as a result of infections caused by resistant bacteria and 22.5 million suffer from hearing impairment, with 2 million profoundly deaf.

Stanford research recently published in the Journal of Clinical Investigation has shown that it is possible to chemically modify aminoglycosides to diminish ototoxicity while maintaining antibacterial activity. Through a novel collaboration between Stanford and University College London (UCL), the aim of this research is to use a results-guided drug design approach to develop the next generation of safer aminoglycoside antibiotics. For this work, the candidate will have access to 15 novel patented aminoglycoside compounds, crystallography data, murine in vitro and in vitro models of ototoxicity, and a rare biobank of cells from patients with the m.1555A>G mutation. This work will build upon the candidate’s Distinction Masters of Research structural biology experience at Imperial College London, and UCL PhD and recent first-author publication in Human Molecular Genetics related to aminoglycoside ototoxicity.

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