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ERACHRON SIGNED

Eradicating Chronic Infections

Total Cost €

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EC-Contrib. €

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Partnership

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 ERACHRON project word cloud

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

experimental    overarching    upcoming    antibiotic    selective    ad    relapsing    time    tolerant    play    off    simply    cascade    insensitive    hoc    fragment    appear    structure    bacterial    pathogen    tools    ultimately    persister    progression    nmr    trigger    screening    awake    chemists    genetically    unaffected    chemical    chronic    drugs    reservoir    operate    exploitable    complementary    pivotal    intrinsically    potent    insurgence    fill    alarming    molecular    persisters    modulate    protein    sustains    stringent    dynamic    pharmacological    allosterically    unravelled    gap    privileged    designed    resurgence    switch    phenotype    regulated    virtual    treatment    urgent    infection    combined    synthesis    spectroscopy    elusive    last    survival    predictions    infections    possibly    dormant    shut    synergy    drug    biological    sr    structural    regulation    events    cellular    suggests    resistant    propensity    molecules    subpopulation    sensitive    sites    highlight    eradication    small    mechanisms    community    biochemical    revert    decades    prevent   

Project "ERACHRON" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITA DEGLI STUDI DI MILANO 

Organization address
address: Via Festa Del Perdono 7
city: MILANO
postcode: 20122
website: www.unimi.it

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 Italy [IT]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-STG
 Funding Scheme ERC-STG
 Starting year 2018
 Duration (year-month-day) from 2018-02-01   to  2023-01-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITA DEGLI STUDI DI MILANO IT (MILANO) coordinator 1˙500˙000.00

Map

 Project objective

'Given the alarming progression of chronic and relapsing infections in the last decades, and the even more alarming predictions for the upcoming years, it is urgent for chemists to be able to provide new molecular tools to study, and ultimately solve, these complex biological problems. Bacterial persisters are an elusive 'dormant' phenotype that play a pivotal role in chronic infections, with mechanisms that remain to be fully unravelled. Current knowledge suggests that bacterial persisters are not genetically resistant to antibiotic treatment; they simply appear to shut down through a cascade of biochemical events called the stringent response (SR), becoming insensitive to current drugs. This subpopulation remains unaffected during the time of pharmacological treatment and represents a reservoir that sustains pathogen survival and resurgence. The goal of this project is to fill the knowledge gap between persisters formation and infection eradication, providing the community with potent and selective small molecular tools that can be used to challenge complementary survival mechanisms. I will adopt a combined approach targeting a specific cellular trigger of the persister phenotype with small molecules designed ad hoc in order to switch it off. The target is a bacterial protein involved in the SR cascade, whose activity is proposed to be allosterically regulated. Coordination propensity analysis of the dynamic behaviour of the target will highlight regulation sites exploitable to modulate and control the protein activity. Structure-based design, virtual fragment screening and chemical synthesis will operate in synergy. Experimental screening methodologies intrinsically rich in structural information, such as those based on NMR spectroscopy, will be privileged. The overarching goal is to identify molecules able to prevent the insurgence of the 'dormant' drug-tolerant state and, possibly, revert the persisters already present to the 'awake' drug-sensitive phenotype.

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 Publications

year authors and title journal last update
List of publications.
2019 Gabriele Conti, Marco Minneci, Sara Sattin
Optimised Synthesis of the Bacterial Magic Spot (p)ppGpp Chemosensor PyDPA
published pages: , ISSN: 1439-4227, DOI: 10.1002/cbic.201900013
ChemBioChem 2019-09-02

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

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