PhD Studentship - BBSRC iCASE: Re-wiring the Sporulation Pathway to Prevent Strain Dispersion (MED1566)

The bacterial endospore is one of the most highly resistant life-forms on earth and allows the organism to survive exposure to extremes of temperature, desiccation, disinfectants and radiation. The longevity of survival is astounding and can be measured not in tens or hundreds of years but in millions. These properties make spore-based delivery systems an ideal pharmaceutical for targeting engineered bacteria to various biome-specific infectious agents, diseases and disorders. Relatively simple to prepare and purify, once made spores are remarkably suited to long-term storage. They are easy to administer/apply and once delivered rely on an entirely natural process (germination) to become transformed into the active agent – vegetative cells. However, the very properties that make spores an ideal delivery vehicles also compromise their perceived safety, as the in situ conversion of an relatively sensitive vegetative cell to an endospore (sporulation) leads to a highly resistant agent that can be dispersed to, and survive in, the external environment indefinitely.

To counter the risks posed, Synthetic Biology will be used to re-wire the sporulation pathway such that the bacterial delivery system only produces spores in the presence of specific exogenous inducers that are absent from the target niche. The availability of such a conditionally sporulating (Spoc) strain will allow the generation of high spore titres under laboratory conditions, but once germinated in the target biome the bacterium remains as vegetative cells and are unable to sporulate again. Such a sophisticated form of disablement will ensure that dissemination of the organism is avoided, thereby satisfying the concerns of regulatory agencies.

The project will focus on the positioning of known, and as yet unknown, genes essential to sporulation under the control of inducible promoters that are reliant on inducers that will not be encountered in the targeted niche.  Initial work will test the suitability of the hybrid riboswitch-based promoter developed in the SBRC 

This project will be based in the BBSRC/EPSRC Synthetic Biology Research Centre (SBRC) of the Biodiscovery Institute and will be supervised by Professor Nigel P Minton. The PhD is in collaboration with the company FOLIUM SCIENCE who are using Guided Biotics™ act to maintain healthy animals and plants, by selectively reducing unwanted bacteria, particularly pathogens, in the target microbiomes, including that of the soil.

How to apply: Applicants should be submitted via https://www.nottingham.ac.uk/bbdtp/case-2020/case-2020.aspx, and ask your referee to submit their reference via https://www.nottingham.ac.uk/bbdtp/apply/submit-references.aspx.

This fully-funded studentships is available to UK students and EU students who have lived in the UK for 3 years prior to the start of their studies. EU students who do not meet this criteria are eligible for a fees-only award.

Application should also be sent via email with the subject line ‘BBSRC iCASE Studentship’ to loretta.waddon@nottingham.ac.uk by the deadline: noon, Tuesday 12th May 2020.

References should be sent directly from the referees to nigel.minton@nottingham.ac.uk by the deadline: noon, Friday 15th May 2020. Please note it is the applicant’s responsibility to ensure that the references are sent in good time for the deadline.

Closing Date: 12 May 2020
Category: Studentships