Klebsiella pneumoniae is a ubiquitous bacterium that can inhabit a broad variety of host and environmental niches; from the human gut, to companion and agricultural animals, wild animals, plants, insects and soils. It is also an important cause of human and animal disease, and a major player in the global spread of antibiotic resistance. Recent genomic analyses have shown that K. pneumoniae is an extremely diverse organism and that gene content can differ substantially between strains. A single strain carries approximately 5500 genes but only 1700 of these are shared across the species. The remaining ~3800 are drawn from a gene-pool that exceeds 100,000 genes, with more than a third predicted to be involved in metabolism. These data indicate that metabolic capabilities vary substantially between strains, and we hypothesise that this is a key driver of adaptation to different ecological niches. Better understanding of this phenomenon will reveal key insights into the evolution of this bacterium. It will also help us to interpret the movement of strains between niches, and subsequently identify the most important routes of transmission into human and animal host populations. In this project the student will combine the latest genomic analysis and computational metabolic modelling techniques with laboratory growth experiments to: i) build high quality genome-scale metabolic models for K. pneumoniae that link gene content information to predicted metabolic protein functions ii) predict metabolic growth capabilities of strains isolated from different ecological niches (different host animals and the environment) iii) identify and validate associations between metabolic capabilities and ecological niche The project is best suited for a PhD candidate interested in the application of computational biology approaches (including command-line programs) to analyse and interpret large datasets. Prior experience using the Unix operating system and the Python or R programming languages is preferred but not essential. Background in microbiology, genetics and/or evolution would also be helpful but not essential. The successful candidate will be co-supervised by Prof Kathryn Holt and Dr Kelly Wyres in the microbial genomics lab at Monash University’s Department of Infectious Diseases (Alfred Hospital campus), and will have the opportunity to interact with collaborators at the University of California San Diego (USA) and Institut Pasteur (France). The project is fully funded for Australian domestic students. International students are subject to additional tuition fees. See https://holtlab.net/ for more information.
bacterial genomics, metabolism, computational biology, ecology, evolution, Klebsiella pneumoniae
Central Clinical School