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Investigating the role of undecaprenyl metabolism in the biogenesis of the outer membrane of Escherichia coli

A project aimed at investigating the control of undecaprenyl metabolism in the biogenesis of the E. coli cell envelope is available at the Centre for Biomedical Science Research, Leeds Beckett University. Undecaprenyl is an essential carrier for multiple bacterial cell wall components such as peptidoglycan, lipopolysaccharide (LPS) and surface antigens. However, the regulatory processes underpinning both the synthesis and recycling of this molecule are poorly understood. This project will use both traditional biochemical and microbiology methods coupled with cutting-edge computational modelling techniques, to probe the biological importance of each of these mechanisms. A greater understanding of this molecular pathway will allow the design of new antimicrobial strategies to combat bacterial infection and disease.

The criteria listed below will be used in selecting those applicants who will be called for interview and those who will be successful in securing a PhD Studentship

  • Candidates require a 1st or upper 2nd class B.Sc honours degree in either biochemistry, microbiology or a related subject
  • a strong interest in computational biology and its application to drug discovery, will be an advantage

This PhD is funded by Oppilotech Ltd [www.oppilotech.com] and Leeds Beckett University, and provides a stipend of £14,553 pa and covers PhD fees for a three-year period. The studentship is available with a February 1st 2018 start date.

Applicants should apply through Leeds Beckett graduate school: Researchadmissions@leedsbeckett.ac.uk.

Applicants should submit the following:

  • A completed application form and a full CV
  • Copy of Photo page from passport
  • Certificates and transcripts
  • Proof of English (for EU/international applicants only IELTS, PEIRSONS OR TOEFL
  • Certificates and transcripts
  • Ensure all sections of the application are completed
  • Photo page from passport received

Closing date for applications is Sunday 3
rd December 2017.

For further information about the project please contact Dr. John George or Professor Gary Jones.

****Closing date for applications midnight, Sunday 3rd December 2017****

1 Year Master of Research MRes available in Biomedical Sciences starting 1st February 2018

Project title: Gliotoxin production and transport in the opportunistic human pathogen Aspergillus fumigatus

Aspergillus fumigatus is an important human pathogen that primarily causes disease in immunocompromised individuals [Invasive Aspergillosis]. With development of resistance to front-line antifungal treatments, there is a need to develop novel therapeutic strategies for hard to treat fungal diseases. Gliotoxin is a mycotoxin produced by A. fumigatus and other fungi, and gliotoxin producers have developed a self-protection mechanism against the toxin. By developing a thorough understanding of the production, regulation and transportation mechanisms of gliotoxin, the possibility exists to sensitise the fungus to its own mycotoxin. This project has two main aims; a) the development of an in vitro assay to identify membrane proteins that are involved in the transportation of gliotoxin, b) a genetic and proteomic analysis of environmental conditions that cause gliotoxin sensitivity.

This project will provide training in yeast and fungal genetics, protein purification and biochemical assay development in addition to cutting-edge proteomics and mass spectrometry analysis.

The project is a collaboration between Prof. Gary Jones, Dr. Vincent Postis at Leeds Beckett with Prof. Sean Doyle at Maynooth University, Ireland. The successful candidate will be required to spend time working at both Leeds Beckett and Maynooth.

Key publications from the Principal Investigators include:

  • Dolan et al. (2017) Structural, mechanistic and functional insight into gliotoxin bis-thiomethylation in Aspergillus fumigatus. Open Biology. Feb;7(2). pii: 160292. doi: 10.1098/rsob.160292.
  • Lee et al.  (2016)  A method for detergent-free isolation of membrane proteins in their local lipid environment. Nature Protocols. 20 Jul;11(7):1149-62.
  • Owens et al. (2015) Interplay between Gliotoxin Resistance, Secretion and the Methyl/Methionine Cycle in Aspergillus fumigatus. Eukaryotic Cell. 14(9): 941-957.
  • Schrettl et al. (2010) Self- protection against gliotoxin- a component of the gliotoxin biosynthetic cluster GliT, protect Aspergillus fumigatus against exogenous gliotoxin. PLOS Pathogens 6(6): e1000952.
  • Funding covers MRes fees for 1-year and provides a stipend of £14,553.

For further information contact Professor Gary Jones.

Applications should be made through the Leeds Beckett Graduate School using the appropriate application form. Applicant’s should also submit a full CV. There is no requirement to submit a project proposal. Closing date for applications is midnight on Sunday 3rd December.

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