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Honours Projects Currently Available

The McDevitt laboratory has a range of multidisciplinary projects on offer in 2017 that combine molecular microbiology, microbial genetics and protein biochemistry to study the virulence mechanisms of major bacterial pathogens. A project in our lab will provide you with a strong set of research skills ideally suited for a job in science or further PhD research.

For more information see below for some of our potential Honours projects or download a summary. If you have any questions or want more contact me to set up a time to talk.

  • 1. Biochemical and biophysical basis of pneumococcal disease

    All pathogenic organisms, whether bacterial, viral or parasitic, require metal ions (e.g. manganese, iron and zinc) to mediate disease. These metals are stolen directly from the host and so the pathways that the pathogen uses to scavenge these essential ions are ideal targets for novel antimicrobials. This Honours project will investigate the unique metal ion uptake and management pathways in the major human pathogen Streptococcus pneumoniae. This will provide crucial information for our drug development research program.

    This project will develop skills in:

    • Gene cloning and routine PCR
    • Gene transcription analyses by qRT-PCR and RNAseq
    • Generating mutant bacterial strains
    • Expressing and purifiying recombinant proteins
    • Setting up and performing crystallisation trials
    • Structure/function analyses of recombinant proteins
    • Performing inductively coupled plasma mass-spectrometry
    • Mapping metal cofactors in bacteria by metalloproteomics
    • Using advanced spectroscopic tools to perform biochemical assays
  • 2. Structure and function of solute-binding proteins in pathogenic bacteria

    All prokaryotes employ solute-binding proteins to recruit metal ions (e.g. Mn, Fe and Zn) for their transporters. This process is essential for their survival as they must acquire these micronutrients to survive in the host environment. Despite the importance of these proteins, the molecular basis of their interaction with metal ions is poorly understood. This Honours project will investigate the structure and function of cation binding proteins. Your work will allow us to understand how these proteins bind and release their ion cargo so that we can use this knowledge to develop novel drugs.

    This project will develop skills in:

    • PCR and qPCR
    • Gene cloning
    • Protein expression and purification
    • Biochemical assays
    • Fluorescence assays
    • Crystallisation
    • Metal content analyses (inductively coupled plasma mass spectrometry)
    • Isothermal titration calorimetry
  • 3. Zinc homeostasis in Pseudomonas aeruginosa

    Pseudomonas aeruginosa is a major opportunistic human pathogen and the leading cause of death in cystic fibrosis. Our recent studies have identified the major pathways involved in zinc uptake from the extracellular environment. This project will use our detailed transcriptional insights to assess the roles of these major, yet uncharacterised, proteins and how they influence the growth and behaviour of P. aeruginosa. This study will define the poorly understood pathways used in Gram-negative bacteria for zinc uptake.

    This project will develop skills in:

    • Gene cloning and routine PCR
    • Gene transcription analyses by qRT-PCR
    • Generating mutant bacterial strains
    • Biofilm formation and phenotypic growth assays
    • Expressing and purifiying recombinant proteins
    • Spectroscopic biochemical assays (e.g. UV-Vis, fluoresence)
    • Membrane fluidity and lipidomic analyses
    • Scanning and transmission electron microscopic analyses
    • Metal content analyses (inductively coupled plasma mass spectrometry)
  • 4. Acinetobacter baumannii and its response to zinc stress

    This project is in collaboration with Dr Bart Eijkelkamp

    The opportunistic bacterial pathogen Acinetobacter baumannii is a major problem in hospitals with the prevalence of infections caused by highly multidrug-resistant strains on the increase. Hence, there is an urgent need for the development of novel treatment strategies to combat A. baumannii infections. Zinc is crucial for A. baumannii to cause disease, however, in excess these ions can also produce significant toxicity. Therefore, our research studies the potential of targeting the A. baumannii zinc homeostasis mechanisms as a novel avenue for treatment. Through extensive bioinformatic and transcriptional studies we have recently identified multiple transporters that play a role in A. baumannii zinc homeostasis. In the proposed project, you will identify and characterise the gene regulators that activate their transcription during zinc stress. Additionally, your project will examine the role of the A. baumannii zinc transporters, and their regulators, in survival within the host environment.

    As part of this project you will apply a broad range of techniques to study A. baumannii zinc homeostasis, which includes:

    • Bacterial fitness analyses (zinc stress, gene knockout mutants)
    • Bioinformatics (comparative genomics, regulatory element identification)
    • Metallomics (bacterial metal accumulation)
    • Gene transcription analyses (qRT-PCR and RNA sequencing)
    • Lipidomics (membrane fatty acid analyses)
    • Cell culturing (lung epithelial cells and macrophages)
    • Mouse infection models (bacterial mutants)
  • 5. Co-evolution of heavy metal and drug resistance genetic elements in pathogenic bacteria

    This project is in collaboration with Prof. Darrent Trott (SAVS) and Dr Sam Abraham (Murdoch Uni)

    Recently we isolated a carbapenem-resistant Salmonella enterica strain that is resistant to 9 classes of antimicrobials as well as a range of heavy metals. This resistance profile arises from a large plasmid that contains both antibiotic and heavy metal resistance associated genes. Similar plasmids have now been isolated from other pathogenic bacteria in Australia and Asia. This project will investigate the mechanisms of heavy metal resistance and explore the hypothesis that heavy metals in the environment are co-selecting for resistance to antibiotics. For further details about this project and it's industry links please contact me.

Chemical Biology of Bacterial Pathogens Laboratory
Address

North Terrace Campus
Level 4, Molecular Life Sciences
The University of Adelaide
SA 5005
AUSTRALIA

Contact

Chris McDevitt
T: +61 8 8313 0413
F: +61 8 8313 7532
Email