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whyBOTher SIGNED

Why does Clostridium botulinum kill? – In search for botulinum neurotoxin regulators

Total Cost €

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EC-Contrib. €

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Partnership

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 whyBOTher project word cloud

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

fitness    gas    genomic    natural    strategies    life    effort    poisonous    vaccine    enteritis    ranging    kills    unprecedented    antitoxin    introduces    plausible    experimentally    quantities    toxigenic    evolution    devastating    fluorescent    explore    bacteria    biology    mankind    silence    stably    mild    metabolic    humans    genetic    nanogram    toxins    feed    social    whybother    bot    agricultural    environments    animals    innovative    epigenetic    notorious    attenuate    synthesis    advantage    first    food    physical    toxigenesis    regulation    paradigm    plastic    sectors    selective    bacterial    cell    populations    gangrene    coordinate    substance    force    neurotoxin    give    regulator    found    necrotic    repressor    emergence    extend    clostridium    tetraplegia    diseases    probably    pathogen    dimensions    encourage    cells    observations    cultures    lines    functional    subpopulations    networks    habitats    utilized    shift    medical    producing    population    environment    botulinum    single    blocks    regulatory    toxin    cellular    reduce    botox    endows   

Project "whyBOTher" data sheet

The following table provides information about the project.

Coordinator
HELSINGIN YLIOPISTO 

Organization address
address: YLIOPISTONKATU 3
city: HELSINGIN YLIOPISTO
postcode: 14
website: www.helsinki.fi

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 Finland [FI]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-CoG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2021-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELSINGIN YLIOPISTO FI (HELSINGIN YLIOPISTO) coordinator 2˙000˙000.00

Map

 Project objective

Bacterial toxins cause devastating diseases in humans and animals, ranging from necrotic enteritis to gas gangrene and tetraplegia. While toxin synthesis probably endows these bacteria with a selective advantage in their natural habitats, toxigenesis is likely to represent a fitness cost. It is thus plausible that mild environments encourage bacteria to give up toxin production, or reduce the number of toxigenic cells in populations. The cellular strategies bacteria use to silence toxin production and to establish stably non-toxigenic subpopulations represent targets for innovative antitoxin and vaccine strategies that can be utilized by the food, feed, medical, and agricultural sectors. I have found the first repressor that blocks the production of the most poisonous substance known to mankind, botulinum neurotoxin (BOT). This toxin, also known as “botox”, kills in nanogram quantities and is produced by the notorious food pathogen, Clostridium botulinum. In whyBOTher, I will extend the knowledge from this single regulator to comprehensive understanding of how C. botulinum cultures coordinate BOT production between single cells and cell subpopulations in response to their physical and social environment, and which genetic and plastic cellular strategies the cells take to attenuate BOT production in short and long term. I will experimentally force evolution of BOT-producing and non-producing cell lines, and explore the genetic, epigenetic, and cellular factors that explain the emergence of the two cell lines. To achieve this goal, I will extend the research on C. botulinum biology in two dimensions: from population level to fluorescent single-cell biology, and from genomic information to functional analysis of regulatory and metabolic networks controlling BOT production. whyBOTher represents an unprecedented research effort into regulation of bacterial toxins, and introduces a shift in paradigm from population-level observations to the life of single bacterial cells.

 Publications

year authors and title journal last update
List of publications.
2020 Maria B. Nowakowska, François P. Douillard, Miia Lindström
Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species
published pages: 19, ISSN: 2072-6651, DOI: 10.3390/toxins12010019
Toxins 12/1 2020-02-03
2017 Mertaoja A, Mascher G, Henriques AO, Korkeala H, Lindström M
First glance into single-cell-level neurotoxin production suggests heterogeneity in neurotoxin production in Clostridium botulinum cultures
published pages: , ISSN: , DOI:
2019-09-02
2017 François Douillard, Yağmur Derman, Gerald Mascher, Hannu Korkeala and Miia Lindström
Natural Genetic Polymorphism and Population Heterogeneity in Clostridium botulinum Strain ATCC 3502
published pages: , ISSN: , DOI:
2019-09-02
2019 Cédric Woudstra, Miia Lindström
BoNT phage instability in Clostridium botulinum Group III
published pages: , ISSN: , DOI:
2019-09-02
2018 Cédric Woudstra, Miia Lindström
Clostridium botulinum group III BoNT phage genetic diversity, p411
published pages: , ISSN: , DOI:
2019-09-04
2018 Cédric Woudstra, François P. Douillard, Miia Lindström
Whole genome comparison of toxigenic and non-toxigenic Clostridium botulinum Group II strains
published pages: , ISSN: , DOI:
2019-09-02
2017 Gerald Mascher, Anna Mertaoja, Hannu Korkeala, Miia Lindström
Neurotoxin synthesis is positively regulated by the sporulation transcription factor Spo0A in Clostridium botulinum type E
published pages: 4287-4300, ISSN: 1462-2912, DOI: 10.1111/1462-2920.13892
Environmental Microbiology 19/10 2019-06-18

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