The role of alarmones in bacterial stress responses
In their natural environments, including host cells in the case of intracellular pathogens, bacteria are
faced with a multitude of stresses such as nutrient limitation, hypoxia and oxidative stress. We are
researching into how the Actinobacteria produce adaptive responses to survive potentially-lethal
stresses. The Actinobacteria constitute one of the largest and diverse bacterial phyla and includes
major human pathogens such as the causative agent of tuberculosis Mycobacterium tuberculosis, as
well the life-saving Streptomyces genus, which is the source of most clinically-important antibiotics
and many anti-cancer therapies.
Bacteria produce “alarmones” when stressed that act as secondary messengers to mediate adaptive
changes in gene expression. However, the cellular targets and mechanisms of action of these small
molecules are poorly understood. This project will focus on the role that alarmones play during
oxidative stress, of particular relevance to the survival of Mycobacterium tuberculosis in the hostile
environment of the human macrophage.\
This project is a collaboration between two molecular microbiology laboratories at the University of
Sussex (School of Life Sciences) and Brighton and Sussex Medical School. Students will receive
training in microbiology, biochemistry and molecular biology, apply modern genomic techniques
such as RNA-seq, and develop their research and transferable skills supported by the Sussex
Postgraduate Skills Programme.
References related to research topic:
Tabib-Salazar, A., B. Liu, P. Doughty, R.A. Lewis, S. Ghosh, M.L. Parsy, P.J. Simpson, K. O'Dwyer,
S.J. Matthews & M.S. Paget, (2013) The actinobacterial transcription factor RbpA binds to the
principal sigma subunit of RNA polymerase. Nucleic Acids Res 41: 5679-5691.
McLaughlin, K.J., C.M. Strain-Damerell, K. Xie, D. Brekasis, A.S. Soares, M.S. Paget & C.L.
Kielkopf, (2010) Structural Basis for NADH/NAD(+) Redox Sensing by a Rex Family Repressor.
Mol Cell 38: 563-575.
Waddell, S. J., N. J. Garton, A. L. Sherratt, S-M. Lee, R. J. Smith, C. Senner, J. Hinds, K. Rajakumar,
R. A. Adegbola, G. S. Besra, P. D. Butcher and M. R. Barer (2008). Cytological and transcript
analyses reveal fat and lazy persister-like bacilli in tuberculous sputum. PLoS Medicine; 5(4) e75.
Please contact Dr Mark Paget (M.Paget@sussex.ac.uk) for more information.
Application process:
To be considered for a place you will need to complete our online application which can be found at
http://www.sussex.ac.uk/study/pg/applying/
Apply for 2014 entry, September start. Mention the name of the supervisor in “suggested supervisor”
section. In funding section mention sponsored or seeking funding. In Award details mention School of
Life Sciences funded studentship.
Documents required: A brief statement of interest in the project (upto 2 pages), full CV, two
academic references, UG/PG transcripts and IELTS/TOEFL results if you are residing in EU.
Funding: The studentship is for 3.5 years (and includes full fee waiver for 3.5 years, stipend Research
Council equivalent rate, £13,726 in 2013; and 50 hours teaching as part of studentship). Only full time
students will be accepted.