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INCAGE

In vitro reconstitution and single cell analysis of the Shigella-septin cage.

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 INCAGE project word cloud

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

bacterium    mostowy    caging    single    completion    assemblies    refractory    influence    defence    reticulum    intracellular    structures    transiently    survival    cytoskeleton    host    components    metabolically    stress    mediating    discovered    parallel    replicate    human    action    reveal    purify    antibiotics    degradation    entrap    counteract    cell    cage    imposed    pathogenic    alive    mechanism    lethal    autophagy    50    cages    death    interacts    flexneri    precise    mostly    unknown    cytosolic    filaments    replication    modulate    complexes    stay    entrapped    mechanisms    membranes    persistence    auxiliary    assembly    cope    infections    follow    rings    shown    subpopulation    biology    assemble    bacterial    bacteria    mitochondria    persister    negative    efficient    septin    gram    antibacterial    immunity    actin    cells    shigella    recognize    pathogen    incage    endoplasmic    lab    fate    reconstitute    uncover    led    vitro    septins    inactive    autonomous    enteroinvasive   

Project "INCAGE" data sheet

The following table provides information about the project.

Coordinator
LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER 

Organization address
address: KEPPEL STREET
city: LONDON
postcode: WC1E 7HT
website: http://www.lshtm.ac.uk/

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 United Kingdom [UK]
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-08-01   to  2019-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE ROYAL CHARTER UK (LONDON) coordinator 53˙507.00
2    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) participant 129˙947.00

Map

 Project objective

Autophagy, an intracellular degradation process, is an important defence mechanism against pathogenic bacteria, including the Gram-negative enteroinvasive human pathogen Shigella flexneri. Work has shown that septins, a component of the cytoskeleton that interacts with membranes, entrap cytosolic Shigella in cage-like structures for targeting to autophagy. However, the factors mediating septin cage formation are mostly unknown. The Mostowy lab has recently discovered that mitochondria are required for efficient septin cage assembly and that ~50% of entrapped Shigella are metabolically inactive. The precise fate of septin cage-entrapped bacterium (replication, persistence, death) remains to be defined. For my project, called INCAGE, I will reconstitute the septin cage in vitro and study host and bacterial factors that modulate septin assembly. I will purify septin complexes and reconstitute septin assemblies (filaments, rings, cages) in vitro, and investigate how auxiliary components (actin, mitochondria, endoplasmic reticulum) influence septin cage assembly. This will reveal how septins recognize bacteria and how they assemble into cage-like structures. In parallel, I will follow septin cage-entrapped Shigella at the level of the single cell to study the lethal action of septin caging and uncover mechanisms that enable bacterial survival. I will test if the subpopulation of septin cage entrapped bacteria that stay alive, can replicate or led to the formation of persister cells (transiently refractory to stress) able to cope with host imposed stress (antibiotics, autophagy). Completion of these objectives will identify factors that promote septin cage assembly and its lethal action against entrapped bacteria. In depth understanding of septin cage assembly and its antibacterial activity can reveal important information about septin biology and cell-autonomous immunity, and help to design novel approaches to counteract bacterial infections.

 Publications

year authors and title journal last update
List of publications.
2019 Sina Krokowski, Sharanjeet Atwal, Damián Lobato-Márquez, Arnaud Chastanet, Rut Carballido-López, Jeanne Salje, Serge Mostowy
Shigella MreB promotes polar IcsA positioning for actin tail formation
published pages: jcs226217, ISSN: 0021-9533, DOI: 10.1242/jcs.226217
Journal of Cell Science 132/9 2019-11-22
2018 Damián Lobato‐Márquez, Sina Krokowski, Andrea Sirianni, Gerald Larrouy‐Maumus, Serge Mostowy
A requirement for septins and the autophagy receptor p62 in the proliferation of intracellular Shigella
published pages: 163-172, ISSN: 1949-3584, DOI: 10.1002/cm.21453
Cytoskeleton 76/1 2019-11-22
2018 Sonia Rebollo-Ramirez, Sina Krokowski, Damian Lobato-Márquez, Michael Thomson, Ivana Pennisi, Serge Mostowy, Gerald Larrouy-Maumus
Intact Cell Lipidomics Reveal Changes to the Ratio of Cardiolipins to Phosphatidylinositols in Response to Kanamycin in HeLa and Primary Cells
published pages: 688-696, ISSN: 0893-228X, DOI: 10.1021/acs.chemrestox.8b00038
Chemical Research in Toxicology 31/8 2019-11-22
2018 Sina Krokowski, Damián Lobato-Márquez, Arnaud Chastanet, Pedro Matos Pereira, Dimitrios Angelis, Dieter Galea, Gerald Larrouy-Maumus, Ricardo Henriques, Elias T. Spiliotis, Rut Carballido-López, Serge Mostowy
Septins Recognize and Entrap Dividing Bacterial Cells for Delivery to Lysosomes
published pages: 866-874.e4, ISSN: 1931-3128, DOI: 10.1016/j.chom.2018.11.005
Cell Host & Microbe 24/6 2019-11-22
2017 Damián Lobato‐Márquez, Serge Mostowy
Salmonella ubiquitination: ARIH1 enters the fray
published pages: 1476-1477, ISSN: 1469-221X, DOI: 10.15252/embr.201744672
EMBO reports 18/9 2019-11-22

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