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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.

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

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

Leaflet | Map data © OpenStreetMap contributors, CC-BY-SA, Imagery © Mapbox

 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.

'

 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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