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Molecular characterisation of novel pathways for cell envelope protein localisation in mycolic acid-producing actinomycetes (ref: SF18/APP/Sutcliffe)

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  • Full or part time
    Prof I Sutcliffe
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Mycolic acid-producing actinomycetes are of vital economic and medical importance. They include pathogenic species including Corynebacterium diphtheriae, Mycobacterium tuberculosis and Rhodococcus equi as well as industrially important organisms. As the cell envelope is the interface dictating interactions of bacteria with their environments (and engagement in biotechnological processes), we seek to understand better fundamental aspects of cell envelope biology in R. equi and C. diphtheriae. We have recently sequenced several genomes of R. equi as well as C. diphtheriae (Sangal et al., 2015; Sangal et al., 2016; Grosse-Kock et al., 2017) and identified multiple genes encoding membrane-associated, cell envelope and secreted proteins potentially associated with the virulence and exploitable characteristics.
This study will focus on the cell envelope as a site for proteins that are either inserted into or attached (by lipid anchors) to cell membranes using R. equi or C. diphtheriae, as a model. Specifically, two-three candidate genes will be characterised using various approaches of molecular genetics and biochemistry. The project will involve generating gene knock-out strains with the loss of the function and mutant characterisation using molecular approaches including electron microscopy, next-generation sequencing and proteomics to study morphological and biochemical dysfunctions. The impact of the loss of gene functions on strain virulence will be characterised by in vivo survival assays in the macrophages. The restoration of gene functions in mutant strains will be studied using complementation experiments.
This project will be carried out in collaboration with Dr Lynn Dover and Dr Vartul Sangal.

Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.

For further details of how to apply, entry requirements and the application form, see
https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/

Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed. Applications that do not include the advert reference (e.g. SF18/…) will not be considered.

Deadline for applications: 1st July 2019 for October 2019 start, or 1st December 2018 for March 2019 start
Start Date: October or March

Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality and is a member of the Euraxess network, which delivers information and support to professional researchers

Funding Notes

This studentship is only open to self-funding candidates. Self-funding candidates are expected to pay University fees and to provide their own living costs. University fee bands are shown at
https://www.northumbria.ac.uk/study-at-northumbria/fees-funding/pg-fees-funding/postgraduate-research-fees/

Fees for this project are costed at Band 4.

References

Grosse-Kock S, Kolodkina V, Schwalbe EC, Blom J, Burkovski A, Hoskisson PA, Brisse S, Smith D, Sutcliffe IC, Titov L, Sangal V. (2017) Genomic analysis of endemic clones of toxigenic and non-toxigenic Corynebacterium diphtheriae in Belarus during and after the major epidemic in 1990s. BMC Genomics. 18(1):873.
Sangal V, Goodfellow M, Jones AL, Schwalbe EC, Blom J, Hoskisson PA, Sutcliffe IC. (2016) Next-generation systematics: An innovative approach to resolve the structure of complex prokaryotic taxa. Scientific Reports. 6:38392.
Sangal V, Blom J, Sutcliffe IC, von Hunolstein C, Burkovski A, Hoskisson PA. (2015) Adherence and invasive properties of Corynebacterium diphtheriae strains correlate with the predicted membrane-associated and secreted proteome. BMC Genomics. 16 (1). p. 765. ISSN 1471-2164



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