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Probing the organization and function of bacterial toxin-antitoxin complexes


Project Description

Bacterial toxin-antitoxin (TA) modules typically consist of a pair of genes that encode for a stable toxin protein and an unstable cognate antitoxin molecule. TAs are abundant on plasmids and chromosomes. For example, the common laboratory strain Escherichia coli K-12 harbours at least 30 known TA loci and Mycobacterium tuberculosis, the causative agent of tuberculosis, possesses more than 80 TA modules. The unstable antitoxins are degraded under certain conditions to liberate the toxin to exert intracellular damage. The toxins target a range of processes, including the translation machinery, DNA replication, cell division and membrane integrity, thereby causing reversible effects that dampen metabolism and cell growth. TAs are implicated in genome maintenance, defence against bacteriophage infection, biofilm formation and the bacterial stress response, among other functions. Nevertheless, the role of many TAs is uncertain and there is considerable controversy about the influence of TAs on bacterial physiology, growth and survival under adverse conditions. The project involves probing the organization and function of TA complexes in E. coli to provide a better understanding of the contribution of these elements to bacterial growth regulation and control.

Training/techniques to be provided:
Work in the host laboratories encompasses a range of cutting-edge microbiology, molecular biological, biochemical and biophysical techniques that provide an excellent basis for a career in biosciences research. The project particularly will involve gene cloning and manipulation, mutagenesis and sequence analysis, as well as a range of project-specific assays that assess TA activity in E. coli.

Entry requirements:
Candidates are expected to hold a minimum upper second class honours degree (or equivalent) in a related subject and to possess postgraduate experience. A solid theoretical background in molecular biology, e.g., understanding of gene expression and control, is essential. Practical experience in molecular biology techniques, including polymerase chain reaction, molecular cloning and sequence analysis, is required.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website). On the online application form select PhD Microbiology.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References


- Salleh MZ, Karuppiah V, Snee M, Thistlethwaite A, Levy CW, Knight D, Derrick JP (2019) Structure and properties of a natural competence-associated pilin suggest a unique pilus tip-associated DNA receptor. mBio 10:e00614-19.
- Collins R, Karuppiah V, Siebert CA, Dajani R, Thistlethwaite A, Derrick JP (2018) Structural cycle of the Thermus thermophilus PilF ATPase: the powering of type IVa pilus assembly. Scientific Reports 8:14022.
- McLeod BN, Allison-Gamble GE, Barge MT, Tonthat NK, Schumacher MA, Hayes F, Barillà D (2017) A three-dimensional ParF meshwork assembles through the nucleoid to mediate plasmid segregation. Nucleic Acids Research 45:3158-3171.
- Kędzierska B, Hayes F (2016) Emerging roles of toxin-antitoxin modules in bacterial pathogenesis. Molecules 21:E790.
- Hayes F (2016) Probe discovery: disentangling gene networks. Nature Chemical Biology 12:3-4.

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