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Integrated structural, functional and genomic studies of bacterial transcriptomes: model systems, pathogens, small RNAs, deep sequencing, transcriptional regulation, antibiotic production and mRNA degradation


   Faculty of Biological Sciences

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  Prof K J Mcdowall  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

While chromosomes are the molecules of inheritance, it is transcriptomes that represent the functional status of organisms with regard to their stage of development, nutrition, health and environment. An inappropriate or incomplete transcriptome is deleterious to an organism’s growth and survival and as a consequence is continually being checked, modulated and degraded and being refreshed by programmes of transcription.

Our laboratory studies the regulation of gene expression at the level of transcription initiation and mRNA degradation and uses bacteria as model systems. The findings and principles being uncovered extend to homologous and analogous system respectively in eukaryotes. The contexts for our studies are the control of antibiotic production by Streptomyces, structure-function studies of the E. coli degradosome and its components, small RNA biology, and the growth and survival of bacteria of clinical importance.

Training is provided in microbiological and molecular techniques and extends through genomic approaches such as proteomics, deep RNA sequencing and chromatin immunoprecipitation to structure-function studies and chemical biology. Much of our work is done in collaboration, expanding the scope of projects and the research experience.

The laboratory (http://www.astbury.leeds.ac.uk/people/staff/staffpage.php?StaffID=KMcD) has a track record of producing PhD students with multiple publications (see Clarke JE, Romero A. D, Jourdan SS and Stead JA) and skills that have been transferred to research areas as diverse as cancer biology and molecular virology. Postgraduate students from a number of countries including Egypt, Spain, Germany, Mexico, Taiwan, Holland, and China have been supported.

The laboratory has grant funding and access to technical expertise and a number of world-class facilities that for example support imaging, biophysical techniques such as SPR and AUC, and robotic selections.

If interested in the above project area (see http://www.astbury.leeds.ac.uk/join/phd.php), you should contact Dr. Kenneth McDowall as soon as possible ([Email Address Removed]; 44-(0)113-343 3109).

International students can be funded via the Wellcome scheme or an ORS award, while UK and EU students can be funded via the Wellcome scheme and the BBSRC (see http://www.astbury.leeds.ac.uk/join/phd.php).

Funding Notes

International students with funding are currently hosted by the laboratory. Students with self-funding will be considered.

References

A comparison of key aspects of gene regulation in Streptomyces coelicolor and Escherichia coli using nucleotide-resolution transcription maps produced in parallel by global and differential RNA sequencing. (2014). Romero DA et al. Mol Microbiol. 2014 Sep 30. doi: 10.1111/mmi.12810.

Direct entry by RNase E is a major pathway for the degradation and processing of RNA in Escherichia coli (2015).
Clarke JE et al. Nucleic Acids Res. 2015 Feb 1;42(18):11733-51. doi: 10.1093/nar/gku808.

Adjacent single-stranded regions mediate processing of tRNA precursors by RNase E direct entry (2014).
Kime L, Clarke JE et al. Nucleic Acids Res. 2014 Apr;42(7):4577-89. doi: 10.1093/nar/gkt1403.

The regulation of the secondary metabolism of Streptomyces: new links and experimental advances (2011). van Wezel GP, McDowall KJ. Nat Prod Rep. 2011 Jul;28(7):1311-33. doi: 10.1039/c1np00003a

Kime L, Jourdan SS, Stead JA, et al. (2010). Rapid cleavage of RNA by RNase E in the absence of 5' monophosphate stimulation. Mol. Microbiol. 76: 590-604.

Nothaft H et al. (2010). The permease gene nagE2 is the key to N-acetylglucosamine sensing and utilization in Streptomyces coelicolor and is subject to multi-level control. Mol. Microbiol. 75: 1133-1144.

Carpousis AJ, Luisi BF, McDowall KJ (2009) Endonucleolytic Initiation of mRNA Decay in Escherichia coli. Prog. Mol. Biol. Transl. Sci. 85: 91-135.

Resch A, Afonyushkin T, Lombo TB, et al. (2008) Translational activation by the noncoding RNA DsrA involves alternative RNase III processing in the rpoS 5 '-leader. RNA 14: 454-459.

Stead JA, McDowall KJ (2007) Two-dimensional gel electrophoresis for identifying proteins that bind DNA or RNA. Nature Protocols 2: 1839-1848.

Jourdan SS, McDowall KJ (2008) Sensing of 5 ' monophosphate by Escherichia coli RNase G can significantly enhance association with RNA and stimulate the decay of functional mRNA transcripts in vivo. Mol. Microbiol. 67: 102-115.

Callaghan AJ, Marcaida MJ, Stead JA, McDowall KJ, Scott WG, Luisi BF. (2005) Structure of Escherichia coli RNase E catalytic domain and implications for RNA turnover. Nature. 437:1187-91.

Uguru GC, Stephens KE, Stead JA, Towle JE, Baumberg S, McDowall KJ. (2005) Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol Microbiol. 58:131-50.
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