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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.

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

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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