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The Line of Duty: how to maintain a giant linear plasmid in antibiotic-producing Streptomyces (LE_J22DTP)


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  Dr T Le  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The majority of bacterial plasmids are circular, linear plasmids are rare. However, giant linear plasmids are widely distributed in the antibiotic producing genus Streptomyces. This genus accounts for ~80% of antibiotic compounds known today and therefore an understanding of the genetic makeup of this genus is important in the context of antibiotic resistance.

Linear plasmids in Streptomyces are involved in antibiotic production, degradation of aromatic compounds, and in phyto-pathogenicity. For example, the 350-kb linear SCP1 plasmid of Streptomyces coelicolor A3(2) carries the biosynthetic cluster for methylenomycin antibiotic. Accumulated data suggest that giant linear plasmids have played critical roles in the horizontal transfer of secondary metabolism and evolution of Streptomyces genomes. Given the biological significance of these linear plasmids, it is surprising that little is known about how these plasmids get transmitted to the daughter cells, and how they might co-exist with the linear chromosome of the host. 

Motivated by the recent works in our lab on solving the 3D organization of a linear Streptomyces venezuelae chromosome, and on elucidating the mechanism of chromosome segregation by the ParA-ParB-parS system, we aim to better understand the molecular mechanism responsible for the segregation and inheritance of the giant linear plasmid SCP1 in Streptomyces coelicolor A3(2).

The selected student with be provided with excellent skills in microbiology, fluorescence microscopy, cell biology, biochemistry, and next-generation sequencing techniques, making the student highly employable, in both academic and industrial sectors.

The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to UK and international candidates for entry October 2021 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers. All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.

This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Tuesday 25th January, Wednesday 26th January and Thursday 27th January 2022.

Visit our website for further information on eligibility and how to apply: https://biodtp.norwichresearchpark.ac.uk/

Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.


Funding Notes

This project is awarded with a 4-year Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) PhD studentship. The studentship includes payment of tuition fees (directly to the University), a stipend for each year of the studentship (2021/2 stipend rate: £15,609), and a Research Training Support Grant for each year of the studentship of £5,000 p.a.

References

1. Szafran, M. J. et al. Spatial rearrangement of the Streptomyces venezuelae linear chromosome during sporogenic development. bioRxiv 2020.12.09.403915 (2020) doi: 10.1101/2020.12.09.403915 (in press in Nature Communications).
2. Jalal, A. S. et al. A CTP-dependent gating mechanism enables ParB spreading on DNA. Elife 10, e69676 (2021).
3. Kinashi, H. Giant linear plasmids in Streptomyces: a treasure trove of antibiotic biosynthetic clusters. J Antibiot 64, 19–25 (2011).
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