Targeting the Gut Mucosa with Therapeutic Molecules
Prof S Cutting
Dr M Soloviev
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
Bacterial spores (Bacillus species) are dormant bioentities capable of surviving indefinitely in the environment. Approximately 1 m in length these structures carry one chromosome that can be genetically manipulated. For biotechnology they offer great potential for delivery of molecules for therapeutic or prophylactic purposes. For example, as vaccines where antigens can be displayed on the spore surface and delivered by an oral route (Permpoonpattana, Hong et al. 2011). This concept has been tried and tested and shown to work for a number of important human and animal diseases including tetanus, influenza and Clostridium difficile (Hong, Hitri et al. 2017). They can also be used for delivery of anti-cancer drugs, for example Paclitaxel where spores are engineered to display an antibody that targets human cells and co-delivers the cancer drug (Nguyen, Huynh et al. 2013). Finally, and most remarkably, they can display enzymes on their surface that are functional offering a number of uses, for example in improved nutrition (Potot, Serra et al. 2010). We have recently designed a novel method for stably expressing molecules on the spore surface where there is no risk of recombinant spores (as GMOs) proliferating in the environment (Hosseini, Curilovs et al. 2017). This solves a major environmental problem over the deliberate release of GMOs.
As such, it is now possible to fully develop the spores as a delivery vehicle. This project will focus on designing and constructing spores that display a number of important proteins with therapeutic potential. This will include IL-10, a cytokine, linked to reduction of colitis and symptoms of inflammatory bowel disease (Steidler, Neirynck et al. 2003). The second component to this project will be the construction of spores that can deliver a number of anti-cancer drugs. The constructed spores will be characterised and evaluated in vitro and where necessary in vivo to demonstrate efficacy.
Proposed start date September 2018
A three year funded studentship based on Research Council rates including tuition fees and stipend.
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