The aim of the Nottingham iGEM 2018 team’s project, called Clostridium dTox; it’s not so difficile was to engineer a C. difficile bacteriophage (phage), to produce factors that would suppress toxin production. They demonstrated that the latest gene-editing techniques could be used to repress expression of both toxin genes (tcdAand tcdB) by targeting their mRNA.
The ultimate goal is a C. difficile-specific bacteriophage therapeutic which stops toxin production in those cells that are infected with the phage, converting them into health-promoting probiotics. Unlike antibiotics, phage cause no collateral damage to the native gut microbiome.
The 2018 team was awarded a prestigious Gold Medal at the International Genetically Engineered Machine (iGEM) competition in Boston, USA.
The team was also nominated at iGEM for ‘Best New Composite Part’. A composite part is a functional unit of DNA consisting of two or more basic parts assembled together.
For the duration of their project the team were embedded within BBSRC/EPSRC Synthetic Biology Research Centre (SBRC) at Nottingham.
Read more about the project: Clostridium dTox; it’s not so difficile
This is the first year the University of Nottingham has taken part in the iGEM competition, the team is interdisciplinary comprising of biologists, engineers and computational scientists from around the University.
The team's project looked at transforming bacteria with a unique array of existing iGEM systems to produce a unique signal of secondary metabolites, initially using fluorescence as a proof of concept. Eventually, using the system to produce a unique and random configuration of products, as their "key". In order to produce this randomness, alteration of the activity/presence of promoters associated with these metabolites were applied using one of a few methods which were considered by the team.
The team worked over the summer months at the BBSRC/EPSRC Synthetic Biology Research Centre (SBRC) at Nottingham with the final product being presented at the annual Giant Jamboree in Boston, USA in November 2017.
Read more about the project: KEY.COLI