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ESX-4 T7SS SIGNED

Structure/function of a prototypic type VII secretion system from a fast-growing pathogenic mycobacteria

Total Cost €

0

EC-Contrib. €

0

Partnership

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 ESX-4 T7SS project word cloud

Explore the words cloud of the ESX-4 T7SS project. It provides you a very rough idea of what is the project "ESX-4 T7SS" about.

mycobacterium    rgm    opportunistic    lab    holo    complementary    experimental    communities    combine    protein    abscessus    t7ss    esx4    characterization    infections    structure    functional    tuberculous    active    substrate    cell    mab    clinically    eccd    intact    membrane    mechanism    modeling    experiments    integrative    lack    rendering    recognition    inner    microbiology    survive    inactive    infection    eccb    functionally    responsible    dalton    collaborators    survival    tuberculosis    mycp    eccc    crosses    attractive    secretion    substrates    sgm    host    ecce    interdisciplinary    investigation    multiply    except    central    unlike    ecce4    awaited    mycobacteria    pulmonary    virulence    form    genetics    esx    questions    acquired    multidrug    intracellular    resistant    extrapulmonary    deemed    resolution    date    multiple    eagerly    published    data    ancestral    shown    macrophages    slow    possess    13    mediated    function    aring    diverse    biology    components    mtb    structural   

Project "ESX-4 T7SS" data sheet

The following table provides information about the project.

Coordinator		 EUROPEAN MOLECULAR BIOLOGY LABORATORY 

Organization address
address: Meyerhofstrasse 1
city: HEIDELBERG
postcode: 69117
website: http://www.embl.de

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 Germany [DE]
 Total cost 162˙806 €
 EC max contribution 162˙806 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-04-01   to  2021-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EUROPEAN MOLECULAR BIOLOGY LABORATORY DE (HEIDELBERG) coordinator 162˙806.00

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 Project objective

Mycobacterium abscessus (Mab) is an opportunistic-multidrug-resistant non-tuberculous mycobacteria responsible for multiple clinically-acquired infections both pulmonary and extrapulmonary. Unlike many rapidly growing mycobacteria (RGM), Mab is able to survive and multiply within macrophages, similar to slow growing mycobacteria (SGM) such as M. tuberculosis (Mtb). In Mtb, five T7SS (ESX-1-5) have been identified and shown to be essential for intracellular survival (ESX-1), virulence (ESX-1 and ESX-5) or growth (ESX-3). T7SS are composed of five protein components essential for function: EccB, EccC, EccD, EccE and MycP. Except for a low-resolution structure of the holo ESX-5 complex from the host lab at 13 Å resolution, no structural data on any T7SS have been published to date, rendering structural work timely and eagerly awaited by relevant communities. Deemed inactive due to its lack of one of the established T7SS components EccE4, ESX-4 has been considered an ancestral T7SS form. However, Mab possess a fully intact and functional ESX-4, essential for its intracellular survival, rendering it a highly attractive target for an in-depth characterization. Here, I propose an interdisciplinary project that includes both functional and structural investigation. As the 2 M Dalton-holo-complex crosses the Mab inner membrane, experimental structural work will be challenging and require an integrative modeling approach to combine diverse experimental data sets. Complementary infection biology experiments including microbiology, genetics and cell biology will be carried out by collaborators. With this work, I aim to respond to central questions related to T7SS in general and Mab ESX-4 specifically, such as: what is the mechanism of T7SS-mediated secretion? What makes ESX-4 specific and different from other T7SS? What is the specific role of EccE4 to establish a functionally active ESX4? and What are the substrates and specific mechanism of ESX-4 substrate recognition?

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