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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.

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

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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