Functional characterization of Neisserial toxin-antitoxin systems
Fact file
| Duration |
Three to four years full-time |
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| Eligibility |
Self-funded; Home, EU or International Students |
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| Supervisor(s) |
Dr Neil Oldfield
Dr David Turner
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| Application deadline |
No deadline |
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About the project
Toxin-antitoxin (TA) systems are commonly found in both Gram-positive and Gram-negative bacteria and comprise a stable toxin able to stall bacterial replication and an antitoxin that neutralises the activity of the toxin. When under stress conditions, such as nutrient limitation, temperature shock, contact with host cells or exposure to antimicrobials, the antitoxins are degraded leaving the toxin free to arrest bacterial growth. This viable, but non-growing, ‘persister’ state facilitates bacterial survival during stress and increases tolerance to antibiotics. It follows that manipulating bacterial TA systems, which are not found in eukaryotic cells, may result in novel therapeutic interventions to interrupt colonisation, persistence or pathogenesis. We have identified several putative TA loci in available genome sequences of Neisseria meningitidis (meningococcus) and Neisseria gonorrhoea (gonococcus). N. meningitidis is an upper respiratory tract commensal, capable of causing outbreaks of invasive disease, including meningitis and septicaemia, whilst N. gonorrhoea is the causative agent of the sexually-transmitted infection gonorrhoea. This project will investigate the role that TA systems play in these organism’s ability to survive and persist in the host; it will provide training in molecular microbiology, protein biochemistry and tissue culture.
Funding notes
This project is available to self-funded students. Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University.
References
- Lobato-Marquez D, Diaz-Orejas R, Garcia-Del Portillo F. Toxin-antitoxins and bacterial virulence. FEMS Microbiol Rev. 2016 Sep;40:592-609.
- Chan WT, Espinosa M, Yeo CC. Keeping the Wolves at Bay: Antitoxins of prokaryotic type II toxin-antitoxin systems. Front Mol Biosci. 2016;3:9.
- Lee KY & BJ Lee. Structure, biology, and therapeutic application of toxin-antitoxin systems in pathogenic bacteria. Toxins 2016 8(10):E305.
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Functional characterization of Neisserial toxin-antitoxin systems