We focus on two main areas of bacterial genomics: genomic epidemiology, or the study of bacterial pathogen populations, and metagenomics, or the study of bacterial communities.
A detailed introduction to these concepts and the differences between them is available here.
Research in pathogen genomic epidemiology
We use whole genome sequencing to study populations of bacteria that contribute to infectious disease in a variety of settings. This includes in-depth studies of microevolution in specific pathogen populations, using next-generation sequencing technologies to sequence and compare the genomes of hundreds or thousands of closely related isolates of the same pathogen.
In these studies, the minor differences between isolates (e.g. between Salmonella Typhi isolated from different typhoid fever patients in a particular location) are of most interest as they reveal how the pathogen is evolving in response to selective pressures (e.g. exposure to antibiotics, vaccine-induced immunity, or natural host immunity).
- antibiotic resistance
- transmission, infection control and public health
- novel bioinformatics methods to interrogate genome data
- developing bioinformatics tools suitable for use in public health laboratories
Specific pathogens under study
- Klebsiella pneumoniae (hospital acquired infections)
- Acinetobacter baumannii (hospital acquired infections)
- Shigella (dysentery)
- E. coli (diarrhea)
- Salmonella Typhi and Paratyphi A (typhoid fever)
Research in bacterial communities
While some bacteria are pathogenic, meaning they make us sick, most of the bacteria we encounter are not pathogenic and live inside our bodies as commensal microorganisms. In fact, for every human cell in our bodies, there are about 10 bacterial cells. These communities of bacteria are a part of healthy human physiology and are referred to as the ‘human microbiome’.
We use high-throughput sequencing to profile the microbiome of the nasopharynx in cohorts of children, to see how their bacterial communities change during childhood and how the communities are related to the development of non-bacterial disease, including the severity of viral infections of the lung and the development of asthma and allergy.
HHMI-Gates International Research Scholars Program – $US650,000 (2017-2022)
Bacterial population genomics and human disease – $404,884 (2014-2017)
NHMRC Career Development Fellowship #1061409 – KE Holt
How are Klebsiella pneumoniae infections acquired in hospital? – $478,770 (2013-2015)
NHMRC Project Grant #1043822 – KE Holt & AJ Jenney
Identifying key players in the spread of antimicrobial resistance – $789,320 (2013-2015)
NHMRC Project Grant #1043830 – KE Holt, RM Hall, M Inouye, J Zobel
The interaction between the host and pathogen genetics in susceptibility to pulmonary tuberculosis – $379,277 (2013-2015)
NHMRC/A*STAR Targeted Research Grant #1056689 – S Dunstan, YY Teo, CC Khor, M Hibberd M, M Caws, M Inouye, KE Holt
Unravelling enteropathogenic E. coli – $693,820 (2014-2016)
NHMRC Project Grant #1067428 – R Robins-Browne, KE Holt, M Tauschek
A strategic vision to drive the control of enteric fever through vaccination – (2015-2019)
Wellcome Trust Strategic Award – A Pollard, S Baker, G Dougan, V Pitzer, KE Holt, B Grenfell, J Clemens, M Gordon, F Powrie, R Heyderman
Molecular networks and genomics of host response in typhoid fever – $487,813 (2016-2018)
NHMRC Project Grant #1101728 – M Inouye, KE Holt, S Baker, S Dunstan
Systems biology of asthma development in early childhood – $742,750 (2013-2015)
NHMRC Project Grant #1049539 – M Inouye, KE Holt
Stop asthma with immunostimulation – $651,059 (2013-2016)
NHMRC Project Grant #1041983 – P Sly P, PG Holt, KE Holt
A multidisciplinary DNA analysis of modern and ancient Antarctic ice cores – $60,000 (2014-2015)
Joyce Lambert Antarctic Research Seed Funding – M Schultz, KE Holt, J Moreau, A Johnson