Environmental Signalling and Gene Regulation in Klebsiella pneumoniae

Project option 3 (of 5)
Please note only one Ker Memorial Studentship will be awarded in total.
Candidates should contact potential supervisors to discuss projects prior to making an application.

• Environmental stimulation of regulatory networks, relevant for in vivo survival, in the major nosocomial pathogen K. pneumoniae is crucial to understanding the interplay of factors involved in host-pathogen interactions and the persistence of an antimicrobial phenotype.
• RamA is an AraC-type regulator intrinsically encoded in Klebsiella pneumoniae, Enterobacter spp and Salmonella Typhimurium serovar enterica. In previous work, we have shown that RamA regulates genes involved in a multitude of cellular processes within the bacterial cell linked to antimicrobial resistance and virulence. Transcriptome analyses and functional validation of the RamA regulon in K. pneumoniae has shown that genes associated with lipid A synthesis are altered which subsequently results in altered host-microbe interactions.
• Given its role in producing pleiotropic phenotypes, the production of the RamA protein can be triggered as a result of constitutive or transient induction under different environmental conditions. Thus it is likely that studies of the RamA regulon as determined under transient inducible conditions provide a dynamic analysis of the regulatory cascade relevant to Klebsiella survival.
• A key aim of this research proposal is to elucidate the properties of RamA regulation and associated biological outcomes in modulating gene expression under transient inducible conditions.
o Using a transcriptome approach as described previously, RamA-mediated gene expression will be determined under both population and single-cell levels.
o These analyses together with functional biological characterization will determine regulatory influence on genetic heterogeneity in expression and survival.
Main methodologies employed

• Genetic manipulation of a Class II pathogen
• Microbiological techniques-aseptic techniques
• Transcriptome analyses

• Customized single cell microscopy

Edinburgh Infectious Diseases is the network of researchers across the city of Edinburgh with an interest in infectious disease. It includes basic scientists, clinicians, veterinarians, and social scientists and provides a vibrant environment for exciting collaborative research.

As part of our development of ground-breaking multidisciplinary research in infectious diseases, the new Ker Memorial Studentship will be held jointly in the School of Biological Sciences and the Deanery of Biomedical Sciences. It offers the successful student the opportunity to undertake world class research, alongside invaluable career development training in teaching.

Pease see below links to the other 4 possible projects offered for the Ker Memorial PhD Studentship. Please note only 1 studentship will be awarded.

https://www.findaphd.com/search/ProjectDetails.aspx?PJID=79060&LID=3300
https://www.findaphd.com/search/ProjectDetails.aspx?PJID=79066&LID=462
https://www.findaphd.com/search/ProjectDetails.aspx?PJID=79062&LID=3300
https://www.findaphd.com/search/ProjectDetails.aspx?PJID=79063&LID=3300