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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.

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

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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