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  Cracking the non-ribosomal code


   Centre for Biodiscovery

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  Dr David Ackerley, Dr Jeremy Owen  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This work will develop new routes to the synthesis of bioactive peptides by recombining different domains and modules of non-ribosomal peptide synthetases (NRPS). NRPS are large multi-modular enzymes that condense specific - often highly unusual - amino acids into short peptide products that frequently have medical applications. "Cracking the non-ribosomal code" will result in generation of modified NRPS enzymes that produce novel products. This will require understanding how adjoining amino acids are recognised and "proof-read" during peptide bond formation, and development of synthetic biology approaches to efficiently recombine NRPS modules and express them in a non-native host. This work will employ two versatile pigment-synthesising model systems to address these issues, and innovative directed evolution (i.e., random mutagenesis and selection) strategies to promote functionality of the recombinant NRPS enzymes.

In terms of background, applicants should read DF Ackerley (2016) "Cracking the non-ribosomal code" Cell Chemical Biology 23:535-537 to gain a sense of the general project area, and Owen et al (2016) "Generating functional recombinant NRPS enzymes in the laboratory setting via peptidyl carrier protein engineering" Cell Chemical Biology 23:1395-1406 and Calcott et al (2014) "Biosynthesis of novel pyoverdines by domain substitution in a nonribosomal peptide synthetase of Pseudomonas aeruginosa" Applied and Environmental Microbiology 80:5723-5731 to better appreciate the two model systems this project will employ.

Applicants should have the equivalent of a first class BSc(Hons) or Masters degree in Biochemistry, Molecular Microbiology, or related discipline. A strong background in molecular biology is essential, and skills in enzymology, chemistry and microbiology are highly desirable. Please note that a PhD in New Zealand is expected to be 3-4 years in duration, and is full-time in the lab without associated coursework. Applicants will be expected to have previously completed a research dissertation or equivalent. The US 4-year BS degree is generally insufficient for entry into the NZ PhD unless it includes a substantial research internship or similar experience. During their PhD studies there is an expectation that candidates will contribute to (paid) undergraduate laboratory demonstrating, and there may be additional opportunities to gain teaching experience.

Even more essential is that you are a nice and good-natured person, are happy to do your share of common lab duties, and have at least a vestigial sense of humour.

Funding Notes

Although funding has been secured for the project itself, applicants will need to obtain their own PhD scholarship to pay their enrolment fees and living expenses. To obtain a Victoria University scholarship (ca. NZ$25,000 tax free, plus enrolment fees) applicants will need the equivalent of an A grade average or higher at BSc(Hons) level study or have been awarded an A/A+ for their Masters thesis (a track record of high-quality published research can sometimes compensate).The next closing date for Victoria University scholarship applications is July 1.