Fighting Infection, Curing Cancer, Saving the Planet
Lead Research Organisation:
University of Nottingham
Department Name: School of Life Sciences
Abstract
Engineering of Clostridium novyi-NT to enhance efficacy in Cancer Therapy
The unique properties of the bacterial endospore make it the ideal vehicle for the delivery of therapeutic agents to solid tumours, to the human or plant microbiome as well as being essential to the storage and maintenance of cultures used in large scale industrial fermentations. Accordingly, spores have a significant role to play in treatment of cancer, in countering the threat caused by antimicrobial resistance (AMR) in diseases of the human gut as well as in microbial production processes for chemicals and fuels that avoid the exploitation of environmentally damaging fossil reserves.
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. In the current project, these properties will be refined and enhanced by using Synthetic Biology to re-wire the sporulation pathway such that spores are only produced under the required conditions and at a time when they are needed.
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. The suitability of promoters and their inducers will be tested using appropriate reporter genes. Known genes essential to sporulation will be taken from the literature, new targets will be identified using Transposon-directed Insertion Sequencing (TraDIS). Initial work will test the suitability of the hybrid riboswitch-based promoter developed in the SBRC, RiboLac. Alternative systems will also be investigated.
The unique properties of the bacterial endospore make it the ideal vehicle for the delivery of therapeutic agents to solid tumours, to the human or plant microbiome as well as being essential to the storage and maintenance of cultures used in large scale industrial fermentations. Accordingly, spores have a significant role to play in treatment of cancer, in countering the threat caused by antimicrobial resistance (AMR) in diseases of the human gut as well as in microbial production processes for chemicals and fuels that avoid the exploitation of environmentally damaging fossil reserves.
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. In the current project, these properties will be refined and enhanced by using Synthetic Biology to re-wire the sporulation pathway such that spores are only produced under the required conditions and at a time when they are needed.
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. The suitability of promoters and their inducers will be tested using appropriate reporter genes. Known genes essential to sporulation will be taken from the literature, new targets will be identified using Transposon-directed Insertion Sequencing (TraDIS). Initial work will test the suitability of the hybrid riboswitch-based promoter developed in the SBRC, RiboLac. Alternative systems will also be investigated.
People |
ORCID iD |
| Nigel Minton (Primary Supervisor) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/T008369/1 | 01/10/2020 | 30/09/2028 | |||
| 2432063 | Studentship | BB/T008369/1 | 01/10/2020 | 30/03/2025 |