Parasight

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Alexander Webb, Nicolas Kylilis, Kirsten Jensen, Geoff S. Baldwin, Tom Ellis, Paul S. Freemont

Imperial College London, United Kingdom

One of the primary goals of synthetic biology is the application-driven generation of new parts, circuits, and systems to solve problems that as yet have not been adequately addressed. The parasitic infection Schistosomiasis affects over 200 million people worldwide, with estimates suggesting that a further 780 million people are at risk of infection. The causative agents are fluke worms of the Schistosoma genus, and infection only occurs when the cercarial larvae are able to penetrate the skin. To facilitate this, the cercariae secrete an elastase possessing a defined substrate specificity. Our project takes advantage of this property of the cercarial elastase, and has used it to design and create biosensors that are specific in targeting Schistosoma. The design of our biosensor is based on a two-pronged approach, 1) an accurate detection system which is targeted to the cercarial elastase, and 2) an easily measurable output. Using synthetic biology approaches we have engineered the biosensor to be “housed” in two bacterial chassis, Bacillus subtilis and Escherichia coli. The B. subtilis biosensor is a fusion protein that possesses the cell wall binding domain of LytC along with our biosensor component, whilst the E. coli biosensor is composed of the CmpX protein, which traverses the outer membrane, fused with our biosensor component. Both biosensor components are presented to the external environment, and possess the cercarial elastase recognition motif, as well as a streptavidin binding peptide, which can be detected by a streptavidin fluorophore conjugate. Thus when the elastase is present it cleaves the biosensor at the recognition motif site, thereby releasing the detectable component, our streptavidin binding peptide. Here we report and discuss the progress we have made in this exciting and important project.