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Streptomyces venezuelae a next-generation cell-factory for synthetic biology

  • Full or part time
  • Application Deadline
    Friday, February 01, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Streptomyces venezuelae a next-generation cell-factory for synthetic biology

Synthetic biology is beginning to explore new cell-factories for opportunities including biofuels and drugs. In particular, the Streptomyces bacteria are of major interest since they produce a range of natural products, many of which are encoded by so-called “cryptic” biosynthetic gene clusters. These clusters are expected to contain a plethora of new antibiotics and medicinal drugs. Due to their “cryptic” nature, many clusters require external stimuli or stress signals to switch them on in the environment. The development of a specialised Streptomyces synthetic biology chassis could help accelerate natural product engineering and be used to unlock uncharacterised “cryptic” biosynthetic gene clusters. To do this, a comprehensive set of gene expression tools is required to build advanced synthetic gene expression networks in Streptomyces. There is also much to be learnt about how synthetic pathways can be precisely engineered in Streptomyces to explore natural product biosynthesis.

(A) Streptomyces synthetic biology. This project will initially aim to develop synthetic biology gene expression tools for the assembly of synthetic circuits in Streptomyces venezuelae. This strain is used in the biotech industry and is listed within a number of US patents. S. venezuelae also has key advantages such as fast growth and a basic foundation in synthetic biology, with gene expression and genome editing tools (e.g. CRISPR-Cas9) available. Currently there is only a limited set of synthetic biology tools for generalised use in Streptomyces, with many synthetic biology DNA parts restricted to certain species. This project will expand this tool set to include a full complement of orthogonal promoter systems with generalised use in Streptomyces bacteria. A key asset to this project is the use of a custom developed S. venezuelae cell-free protein synthesis system, which can be used for rapid prototyping of genetic circuits in a test-tube (2). This can be used to accelerate the design, build, test and learn cycle paradigm, a key engineering principle of synthetic biology. Here this project will also attempt to demonstrate predictable transfer of genetic circuits from in vitro designs into live S. venezuelae cells.

(B) Natural product engineering. The application of this project is to explore the use of newly developed synthetic biology tools for engineering natural product pathways. This will include validation with known model biosynthetic pathways (e.g. violacein, non-ribosomal peptides), before progressing to uncharacterised “cryptic” biosynthetic gene clusters isolated from the genomes of Streptomyces or related Actinobacteria. It is anticipated this approach will advance the fundamental knowledge in Streptomyces synthetic biology, as well as exploring the use of synthetic biology for accelerating natural product discovery.

Further reading: (1) Phelan RM et al (2015) ACS Synth Biol 4(4):393–399; (2) Moore SJ et al (2017) Biotechnol J:1600678.

The candidate: We are looking for a highly motivated student with a minimum of 2:1 degree in biology, biochemistry or a related subject. Informal enquiries can be addressed to Dr Simon Moore –

Funding: This is funded by the Graduate Teaching Assistantship (GTA), which provides financial support in return for 96 hours of teaching per year. The stipend paid equals the full UK Research Council rate of £14,777 (rate for 2018/19) plus tuition fees at the Home/EU rate. International applicants should make provision to meet the difference between Home/EU and International fees (this will be around £14,000 - amount tbc in March). For further information on the Graduate Teaching Assistantship scheme go to: https://www.kent.ac.uk/scholarships/search/FNADGTA00001

How to apply: Applications can be made using the online University application page where the project title should be entered as the proposed area of research and Dr Simon Moore as supervisor. Please include a CV and a cover letter. Applications must be received by 1 February 2019. The start date is September 2019.

Funding Notes

£14,777 (2018/19 rate) plus Home/EU fees. See View Website

Scholarships will be offered at the standard UK Research Councils’ rate and administered under the Graduate Teaching Assistant Scheme (GTA).

UK, EU and overseas fee paying students are invited to apply. International applicants should make provision to meet the difference between Home /EU and International fees (this will be around £14,000 - amount tbc in March). Please note that overseas students must have the appropriate documentation to evidence eligibility to work in the UK.


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