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Cell-free synthetic biology for natural product discovery


   London Interdisciplinary Biosciences Consortium (LIDo)

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  Dr Simon Moore, Dr Sarah Barry, Dr Lauren Ray, Dr Jana Braesel  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

We are looking for a curious, self-motivated, and collegial applicant to join our team as a PhD student. The project aims to study the potential of synthetic biology for natural product discovery. The student will work on a fully funded four-year BBSRC iCASE studentship starting in 2023. PhD applicants are invited to work within the group of Dr Simon Moore at the School of Biological Sciences, Queen Mary University of London. The iCASE project will also be jointly supervised by Dr Sarah Barry from the School of Chemistry, Kings College London, and by our industrial partners at Syngenta.

Project summary

Agriculture generates £24 billion to the UK economy per year but is under threat from rising levels of crop diseases, antimicrobial resistance, and global warming. With these global challenges in mind, there has never been a timelier opportunity to harness natural solutions to help address these major problems. This PhD project will specifically investigate the potential of natural products for potential application in the agriculture industry.

Background

Environmental microbes and plants are a rich source of natural products, including antibiotics, anti-cancer drugs and agricultural chemicals. Importantly, bacteria contain regions of co-localised genes on their genome, which are referred to as biosynthetic gene clusters. Biosynthetic gene clusters encode the enzymes, and other proteins (e.g., transporters, resistance) required to make natural products. Importantly, because of the extensive diversity of biosynthetic gene clusters available to study (at the millions scale), the prioritisation of novel and/or potentially bioactive BGCs through bioinformatics is an important tool for natural product discovery (Gavriilidou et al., 2022). However, there is a disparity between the number of predicted biosynthetic gene clusters and experimentally characterised natural products. From bacteria alone, the number of chemical classes documented in the Natural Product Atlas (van Santen et al., 2019) is currently ~12,500 chemicals, which is approximately only 3% of the total predicted potential chemical classes (Gavriilidou et al., 2022). Therefore, developing new tools, or methods that increase the throughput of studying biosynthetic gene clusters, will help drive innovation and the discovery of new natural products.

This synthetic biology project aims to engineer biosynthetic gene clusters using an all cell-free approach. To do this, we will use a specialised cell-free transcription-translation system developed by the Moore group (Moore et al., 2021) to study specific biosynthetic gene clusters that encode natural products of interest. Cell-free transcription-translation reactions simply require DNA, cell-extract, energy, and an amino solution to make mRNA, proteins, and small molecules as desired inside a test tube. Here the cell-free system provides an advantage over traditional methods (e.g., bacterial fermentation) to allow us to study natural product biosynthetic pathways in microscale reactions within rapid timescales.

Student training and development

This PhD project will provide the student with a rich package of training and development opportunities across the academic and industry partnership across the supervision partners of Queen Mary University of London, Kings College London, and Syngenta. The PhD project is multidisciplinary (e.g., biology, chemistry, engineering), while the student will also gain specialist knowledge of cell-free transcription-translation systems, a platform technology used by several emerging small-medium enterprises through to large industry groups both within the UK and internationally. In addition, the student will receive continuous supervision and training in transferable skills, such as communication, task management, problem solving, and team working. The Queen Mary Academy also offers general training courses in themes such as presenting, teaching, mindfulness, and wellbeing.

Research environment 

You will work in our fully equipped biology and chemistry labs at Queen Mary University of London and King's College London. The studentship also includes a placement at Syngenta (at least 3 months).

Eligibility Criteria and Candidate Profile

Scholarship opportunities are available to candidates of any nationality. Candidates must hold a first-class degree or a strong 2:1 in biological sciences (e.g., biochemistry, biomedical science, biotechnology, or related discipline). Evidence of chemistry knowledge and/or chemical biology is desired. Additional laboratory experience at master’s level qualification (or equivalent) is beneficial but not essential. We are looking for self-motivated, independent students with excellent communication and team working skills.

English language

All applicants must meet the English language entry requirements for their chosen programmes to study at Queen Mary University of London. Please refer to the following web link for details - https://www.qmul.ac.uk/international-students/englishlanguagerequirements/


Funding Notes

Fully funded place including home (UK) tuition fees and a tax-free stipend in the region of £19,668. Additional funding to cover full overseas fees is available for a maximum of 11 studentships.
This project also comes with an enhanced stipend provided by Syngenta.

References

Gavriilidou, A., Kautsar, S. A., Zaburannyi, N., Krug, D., Müller, R., Medema, M. H., et al. (2022). Compendium of specialized metabolite biosynthetic diversity encoded in bacterial genomes. Nat. Microbiol. 7, 726–735.
Moore, S. J., Lai, H.-E., Chee, S.-M., Toh, M., Coode, S., Chengan, K., et al. (2021). A Streptomyces venezuelae Cell-Free Toolkit for Synthetic Biology. ACS Synth. Biol. 10, 402–411.
van Santen, J. A., Jacob, G., Singh, A. L., Aniebok, V., Balunas, M. J., Bunsko, D., et al. (2019). The Natural Products Atlas: An open access knowledge base for microbial natural products discovery. ACS Cent. Sci. 5, 1824–1833.
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