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 gonorrhoeae (gonococcus). N. meningitidis is an upper respiratory tract commensal, capable of causing outbreaks of invasive disease, including meningitis and septicaemia, whilst N. gonorrhoeae 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.
The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.
Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages http://www.nottingham.ac.uk/graduateschool/funding/index.aspx for information on specific EU scholarships. International applicants should visit our International Research Scholarships page http://www.nottingham.ac.uk/studywithus/international-applicants/scholarships-fees-and-finance/scholarships/index.aspx for information regarding fees and funding at the University.
1. Lobato-Marquez D, Diaz-Orejas R, Garcia-Del Portillo F. Toxin-antitoxins and bacterial virulence. FEMS Microbiol Rev. 2016 Sep;40:592-609. 2. 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. 3. 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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