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PneumoCaTChER SIGNED

The role of cell-to-cell variability in pneumococcal virulence and antibiotic resistance

Total Cost €

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EC-Contrib. €

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Partnership

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 PneumoCaTChER project word cloud

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

gene    phenotypic    models    underlying    populations    pneumococci    variation    engineered    vice    host    outcome    pneumococcal    screening    single    collaborations    therapy    cycle    clonal    imaging    environment    antibiotic    combining    heterogeneity    bacteria    lung    position    epithelial    strategies    driving    opportunistic    cellular    poorly    expression    influences    cells    transcriptomics    pressure    switches    synthetic    hypothesis    mechanisms    within    rates    dual    platforms    helps    exhibit    pathogenic    resistance    biology    immune    crispri    originate    exploited    phenotype    sources    diverse    genetic    places    treatment    infection    unclear    bistable    resist    insights    pathogen    though    cell    rna    perform    reveal    innovative    microbe    human    bacterial    quantitative    excellent    pneumoniae    pathogens    molecular    streptococcus    combined    microfluidics    virulence    elude    infections    versa    overview    grow    engineering    variability    noise    setup    seq   

Project "PneumoCaTChER" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITE DE LAUSANNE 

Organization address
address: Quartier Unil-Centre Bâtiment Unicentre
city: LAUSANNE
postcode: 1015
website: www.unil.ch

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 Switzerland [CH]
 Total cost 1˙999˙735 €
 EC max contribution 1˙999˙735 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-11-01   to  2023-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITE DE LAUSANNE CH (LAUSANNE) coordinator 1˙999˙735.00

Map

 Project objective

Within clonal bacterial populations not all cells exhibit the same phenotype, even though they grow in the same environment. The molecular sources contributing to phenotypic variation are diverse and can originate from noise in gene expression to heterogeneity in growth rates or cell cycle state. Phenotypic variation helps pathogenic bacteria to elude the host immune response or resist antibiotic pressure. Vice versa, there is cell-to-cell variability in the host’s response towards pathogens that can be exploited by bacteria. How the combined cellular heterogeneity of both host and microbe contribute to infection outcome is poorly understood. The role of phenotypic variation on antibiotic resistance development is also unclear.

Recently, we developed novel single cell imaging systems as well as genetic engineering and screening platforms for application to the important opportunistic human pathogen Streptococcus pneumoniae. In addition, we generated a dual-transcriptomics overview of pneumococcal infection of human lung epithelial cells and setup collaborations to perform several infection models. This now places us in an excellent position to investigate the mechanisms and the importance of single cell behaviour for pneumococcal virulence and antibiotic resistance.

The driving hypothesis of this application is that the combined heterogeneity of host cells and pneumococci influences infection and antibiotic therapy outcome. To test this, we will use innovative approaches for infection biology by combining synthetic biology and quantitative single cell biology including single cell RNA-seq, CRISPRi, engineered bistable switches and microfluidics. We will reveal the molecular mechanisms underlying cell-to-cell variability and its importance in virulence and antibiotic resistance.

Insights obtained in this project will lead to a better understanding of phenotypic variation and might result in new treatment strategies for pneumococcal infections.

 Publications

year authors and title journal last update
List of publications.
2019 Jelle Slager, Rieza Aprianto, Jan-Willem Veening
Refining the Pneumococcal Competence Regulon by RNA Sequencing
published pages: , ISSN: 0021-9193, DOI: 10.1128/jb.00780-18
Journal of Bacteriology 201/13 2019-08-29
2019 Lance E. Keller, Anne-Stéphanie Rueff, Jun Kurushima, Jan-Willem Veening
Three New Integration Vectors and Fluorescent Proteins for Use in the Opportunistic Human Pathogen Streptococcus pneumoniae
published pages: 394, ISSN: 2073-4425, DOI: 10.3390/genes10050394
Genes 10/5 2019-08-29
2019 Chryslène Mercy, Adrien Ducret, Jelle Slager, Jean-Pierre Lavergne, Céline Freton, Sathya Narayanan Nagarajan, Pierre Simon Garcia, Marie-Francoise Noirot-Gros, Nelly Dubarry, Julien Nourikyan, Jan-Willem Veening, Christophe Grangeasse
RocS drives chromosome segregation and nucleoid protection in Streptococcus pneumoniae
published pages: , ISSN: 2058-5276, DOI: 10.1038/s41564-019-0472-z
Nature Microbiology 2019-08-29

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