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DiStRes SIGNED

Disentangling the stringent response to engineer novel anti-persister drugs

Total Cost €

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EC-Contrib. €

0

Partnership

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 DiStRes project word cloud

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

difficult    genomic    despite    subpopulations    slow    effectors    catalysed    source    eradicate    treatments    preliminary    biophysical    tolerate    antibiotic    structurally    antipersister    fundamental    designed    biochemical    revolution    primary    settings    candidates    midst    inner    biotech    molecules    modulators    single    discover    keystone    compounds    de    refringent    resolution    stringent    dormant    structures    stress    active    engineering    cell    bacteria    synthesis    strategy    breakthrough    cells    hydrolysis    variety    catalogue    drug    small    microbiology    validate    customized    highlight    tools    accuracy    structural    cellular    workings    mediated    biology    combines    bacterial    drugs    last    turn    molecular    proteins    century    ppgpp    superbugs    modern    spot    novo    modulate    impinge    devised    resistant    modeling    chemical    ways    molecule    enzymes    rsh    guarantees    conventional    screen    persistent    mutations    tolerance    spectrum    broad    infections    group    antibiotics    persisters    rela    mechanisms    exercise    proof    facilitated    pathogens    clinical    experiment    overarching   

Project "DiStRes" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE LIBRE DE BRUXELLES 

Organization address
address: AVENUE FRANKLIN ROOSEVELT 50
city: BRUXELLES
postcode: 1050
website: www.ulb.ac.be

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 Belgium [BE]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (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 2020-09-01   to  2025-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE LIBRE DE BRUXELLES BE (BRUXELLES) coordinator 2˙000˙000.00

Map

 Project objective

Bacterial “superbugs”, refringent to antibiotic treatments, have rapidly increased with the turn of the century. Slow growing, dormant cells (known as persisters) are subpopulations of bacteria that tolerate antibiotics and are considered a primary source of infections for antibiotic-resistant pathogens since they are difficult to eradicate in conventional ways. Mutations in RelA/SpoT (RSH), the effectors of the stringent response, promote antibiotic tolerance and persistent infections and are commonly selected in clinical settings of a variety of pathogens. However, despite the importance of the RSH-mediated stringent response, there is no comprehensive knowledge on the inner workings of the enzymes, or drugs that modulate the bacterial response to stress. Modern structurally biology is currently in the midst of a revolution comparable to that of the Genomic breakthrough of the end last century. This has facilitated access to structural information and increased the accuracy of the modeling and design of de novo structures of proteins and small molecules. Thus my overarching goal is to target key steps in the molecular mechanisms of ppGpp synthesis and hydrolysis catalysed by RSH enzymes, to discover active compounds against persisters. The highlight of this proposal is a new system biology approach that combines cellular microbiology (at a single cell resolution) with structural engineering, biophysical, biochemical and chemical-biology methods to design, screen and validate novel small molecule drug candidates targeting the stringent response. Based on preliminary keystone results from my group, we devised a proof of concept experiment for which we designed a catalogue of novel modulators of the stringent response customized to target bacteria in a specific or broad spectrum way. The success of this exercise guarantees this strategy will not only deliver new antipersister compounds and biotech tools, but will also impinge fundamental research in microbiology.

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The information about "DISTRES" are provided by the European Opendata Portal: CORDIS opendata.

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