Engineering a semi-biotic immune system

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry

Abstract

Synthetic biology is an emerging field that aims to engineer biological systems by utilising engineering principles, analytical technologies and increasing understanding from biological research. Some of the successes in this young field include bacterial production of the anti-malaria drug artemisinin and generation of significant private funding for basic research. We wish to move developments in Synthetic Biology from simple components towards integrated systems with higher functionalities. Specifically, our long-term goal is to design and fabricate a semi-biotic immune device. At its core, the device will use a consortium of engineered bacteria, composed of a group of detectors that monitor the host for signals of disease onset and responders, that await signals from the detecting bacteria, before initiating the production and release of the relevant small molecule treatment. The engineered bacteria will be interfaced with traditional electronic components that oversee, record and transmit the status of the unit. We envisage that this device will enable individual-specific, rapid and autonomic therapeutic intervention at the early stages of disease.

Planned Impact

Impact on UK economy: Exploitation and application The ultimate objective of the proposed research is to engineer a reliable semi-biotic immune system. While achieving this grand goal might be beyond the lifetime of this application, the proposed research plan is expected to lead to several exciting applications, as discussed above. We envisage these to have considerable translational potential. For this reason, we plan to benefit from the expertise and industrial links of our Mentors and, in particular, Dr. Malcolm Rhodes, who is the head of Technical Director of bioProcessUK and Consultant for the biopharmaceutical industry. We will also work closely with our Universities' technology and knowledge transfer services (e.g. Imperial Innovations, etc.) to move our scientific findings towards practical implementation. Finally, we will explore existing links with the bio/pharmaceutical sector, for example AstraZeneca (AT), Lonza Biologics (CK), Avecia (AM) regarding the commercialisation of our research. Impact on public awareness in science The broad field of synthetic biology has generated considerable public interest and has been subject to high media coverage. With its applied nature, the proposed research holds potential to generate similar interest from the public. We will utilise this interest to raise the public awareness for synthetic biology research by organising events at the conjunction of arts and science. We will also engage the public in dialogue on solving the ethical challenges that are bound to arise as we move the synthetic biology field to the next stage of sophisticated applications. Our plan of action in this direction will be shaped in collaboration with renowned ethical scientist. Impact on training young scientists The development of any new field eventually hinges on the influx of talented young people. This project will have a direct impact on the development of young scientists. Each applicant has secured funding from their host Departments to support a PhD studentship. These studentships will be deployed after the first 18 months of the project, when we will decide on which projects to take forward. The students will therefore benefit from a more defined project and will be supervised by at least two applicants. The group will therefore provide an interdisciplinary training environment for several PDRAs, technicians and graduate students directly engaging with the proposed research. These individuals will develop skills in both experimental and theoretical approaches and will become familiar with cutting-edge technologies. Secondly, we will showcase our research through our teaching, as well as our websites, thus encouraging undergraduate and MSc students to enter the fields of synthetic biology. Impact on academic community In terms of scientific developments, we feel that our proposed research can generate several exciting outcomes, which will have a dramatic impact on the UK, Europe and and international academic community. We have outlined these in detail in the Academic Beneficiaries section of this form. The proposed project will raise awareness among the broad research base in the UK of challenges in the synthetic biology field. Our group, like many other synthetic biology teams, is interdisciplinary, composed of a biomolecular engineer, bioprocess engineer, system biologist, chemical biologist, electrical engineer, and microbiologist. Our research findings will therefore be published in a variety of journals and conferences that span the engineering and biological disciplines, making fellow researchers more familiar with this field.

Publications

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Description There have been several key findings from this award, which have been published in 19 peer reviewed publications in leading international journals.

- a microbial system for the fast and cheap expression of three glycosyltransferases. These are enzymes that can change the structure of a certain class of therapeutic proteins that have chains of sugars attached to them. We also developed laboratory techniques to analyse how fast these enzymes work and how effective they are.
- we have developed a series of microfluidic platforms that allow precise manipulation and detection of cells at the single cell level. The importance of single cell study is now well-recognized, since a small subset of cells often play determinant roles in many biological phenomena (e.g. antibiotic resistance, cancer).
- Developing a new computation model for mapping evolution of molecular pathways.
- Several new synthetic biology tools, including light-activated protein production in cells.
- Several new multi-function and responsive hydrogels.
Exploitation Route there have been multiple findings form this work (see above summary). the majority of this work has been published in scientific journals. In several cases this work has already been built upon by us and others.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology