Creating safe strains of Clostridium botulinum for the Food Industry

Marie Skłodowska-Curie ESR Fellowship

The bacterial endospore is one of the most highly resistant life-forms on earth and allows the bacterium to survive exposure to extremes of temperature, desiccation, radiation, disinfectants and, in the case of Clostridium, oxygen. The longevity of survival is astounding and can be measured not in tens or hundreds of years but, in millions. These remarkable structures are the most important single feature of the genus Clostridium. This is because spores play the pivotal role in the spread of infection (eg, C. difficile) and in foodstuff contamination and food poisoning (eg, C. botulinum and C. perfringens). The processes of spore formation (sporulation) and germination (return of the dormant spore to toxin-producing, vegetative cells), therefore, represent key intervention points. On the other hand, the majority of clostridia are entirely benign and can sustainably produce all manner of useful chemicals and fuels. Crucially, the regulation of chemical production is intimately linked to that of sporulation. Spores of benign species may also be used as a delivery system for treating cancer. This is because intravenously injected spores localise to and selectively germinate in the hypoxic centres of solid tumours, a property that can be used to deliver anti-tumour agents. Moreover, the phage-mediated delivery of small, acid-soluble protein (SASP) derived from spores are the basis of an innovative approach to the killing of antibiotic resistant bacteria. Yet, despite the tremendous importance of the spore, little is known of the developmental processes of clostridial sporulation and germination. Deriving this knowledge, and thence exploiting it, is the objective of the Marie Curie ITN CLOSPORE.

The Project

The neurotoxin produced by Clostridium botulinum is the most toxic substance known to man and is the causal agent of food-borne botulism. The contamination of food products with C. botulinum has been the principle target of the food industry for over a century. To prevent food-borne botulism, it is imperative to understand those factors that affect the ability of the organism to grow and/or produce toxin when present in food. The requisite studies are impeded by the highly toxic nature of the organism. In this project you will use advanced molecular biology tools and Synthetic Biology approaches to generate ‘safe’ strains of C. botulinum and to develop real-time assays for clostridial growth, toxin production and spore formation/germination.

The project is with the Clostridia Research Group (CRG) of the BBSRC/EPSRC Synthetic Biology Research Centre (SBRC) located at the University of Nottingham (http://www.sbrc-nottingham.ac.uk/). The CRG (60+ researchers) are one of the largest research groups in the world focused on the genus Clostridium and occupy ‘state-of-the-art’ facilities within the SBRC.

The Network

CLOSPORE is a new Marie Skłodowska-Curie Actions ITN, based at centres of excellence in Lisbon, Helsinki, Paris, Wageningen, Abingdon and Nottingham. There are eight participating organisations involved, composed of four academic institutions and four companies. Across the network a total of 15 early stage researchers will have the opportunity to study for three years towards a PhD in microbiology. Participants will be generously paid with all the benefits of an employee, and will have the opportunity to join network-wide training events, collaborations and conferences.

Further details, including how to apply, are available at www.clostridia.net/clospore