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Investigating the genomic and metabolic impacts of insertion sequences in Klebsiella pneumoniae rhinoscleromatis

Klebsiella pneumoniae and related species from the genus are considered leading causes of infections in hospital settings globally. They cause a range of infections, commonly arise in immunocompromised hosts and typically manifest as urinary tract, respiratory (pneumonia), wound and bloodstream infections. A rarer occurrence but considered endemic in some low/middle income regions around the globe is rhinoscleroma, characterised as a chronic granulomatous disease that affects the nasal cavity and upper respiratory tract. The causative agent is a genetically-distinct sub lineage of K. pneumoniae that has been typed as sequence type 67 and is also referred to as K. pneumoniae rhinoscleromatis. There are several genetic features that appear to distinguish ST67 K. pneumoniae rhinoscleromatis from other sub lineages of K. pneumoniae including those related to virulence; a K3 capsule type and unique variants of key virulence determinants (yersiniabactin, aerobactin and hypermucoidy-conferring rmp locus). Further, these genomes also appear to have significantly higher loads of insertion sequences (IS) compared to other sub lineages of K. pneumoniae and species within the genus. Insertion sequences are mobile DNA that can move within/between genomes and impacts of their insertion include DNA recombination, and disruption or up-regulation of genes and/other pathways (i.e. those related to metabolic growth functions). In this project, genomic approaches will first be used to quantify, characterise and compare the loads and types of IS in ST67 and non-ST67 genomes. The impact of IS in ST67 will be explored at both the genomics and metabolic level, with some scope to investigate any key hypotheses further in a lab setting. The project is expected to provide some clarifying insights into the genetic background of ST67 and important properties that may account for the virulence and unique disease profile of these strains. This project will largely utilise techniques in the genomics space including but not limited to de novo genome assembly and annotation, whole genome alignments, mapping of insertion sequences and BLAST. The work is therefore suitable for students with an interest in computational biology and its application in studying bacterial pathogens.
Essential criteria: 
Minimum entry requirements can be found here:
Klebsiella pneumoniae, Klebsiella, bacterial genomics, genomics, bacterial pathogen, infectious disease, comparative genomics
Available options 
Masters by research
Short projects
Time commitment 
Physical location 
Burnet Institute with Monash University in Melbourne, Australia.
Kelly Wyres
Jane Hawkey

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