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Genome sequencing and human susceptibility to Legionella longbeachae infection

A postgraduate research opportunity at the University of Otago.

Details

Close date
Friday, 19 February 2021
Academic background
Sciences, Health Sciences
Host campus
Wellington
Qualification
Honours
Department
Pathology and Biomedical Science (Christchurch)
Supervisors
Professor Martin Kennedy, Dr Sandy Slow, Associate Professor John Pearson

Overview

Severe or fatal pneumonia arising from infection with the bacterium Legionella longbeachae (Legionnaires’ disease) is a major problem in New Zealand, and is a research focus of The Infection Group in this Department. Although many people are potentially exposed to L. longbeachae, particularly through gardening and use of potting mix or compost, only a relatively small number become seriously infected and need to be hospitalised. Many things may impact on susceptibility to infection, but there are several examples of human genetic factors that can lead to a greater or lesser risk of infection with certain pathogens (1-3).

Our hypothesis for this project is that people who suffer severe L. longbeachae infection have a genetic predisposition which makes them more susceptible to such infections.
To test this hypothesis, we have collected blood samples from patients with pneumonia caused by L. longbeachae, who have consented to detailed genetic analyses, and obtained whole genome sequence data on a subset of these patients. This will provide an initial “discovery” cohort of genome sequences that we can examine in several ways using computational methods:

  • we will identify all variants in candidate genes implicated in other human infectious diseases, seeking any that are over- or under-represented in this discovery cohort
  • we will search for all genetic variants that are strongly over- or under-represented in the discovery cohort relative to the known population allele frequency of such alleles
  • we will search for evidence of copy number variation that may impact on susceptibility or resistance to infections

For any such genetic variants that appear promising in the discovery cohort, laboratory assays will be established to allow targeted assessment of allele frequencies in a larger sample of L. longbeachae pneumonia patients who have consented to this study. Major departures in allele frequencies between pneumonia cases and population allele frequencies are suggestive of a role in susceptibility, and would be deserving of further analysis.

Evidence for a role of specific human genetic variants in susceptibility to L. longbeachae infection would be of great relevance both to the understanding of such infections, and potentially to efforts aimed at reducing rates of infection within the community.

References

  • Casanova, J.-L. (2015). Human genetic basis of interindividual variability in the course of infection. Proceedings of the National Academy of Sciences, 112(51), 201521644. https://doi.org/10.1073/pnas.1521644112
  • Chapman, S. J., & Hill, A. V. S. (2012). Human genetic susceptibility to infectious disease. Nature Reviews Genetics, 13(3), 175–188. https://doi.org/10.1038/nrg3114
  • Ko, D. C., & Urban, T. J. (2013). Understanding Human Variation in Infectious Disease Susceptibility through Clinical and Cellular GWAS. PLoS Pathogens, 9(8), 1–4. https://doi.org/10.1371/journal.ppat.1003424

Preferred student expertise

This project is largely computational in nature, and will involve a great deal of bioinformatics analysis, with a smaller component of laboratory work. The ideal background for this would be strong computational skills, including the ability to work in a Unix operating environment. A background in biology or genetics would be an advantage.

Further information

This is one of a number of projects on offer for the 2021 intake of BBiomedSc(Hons) at the University of Otago, Christchurch campus.

Contact

Professor Martin Kennedy
Tel   +64 3 364 0590
Email   martin.kennedy@otago.ac.nz