Tuberculosis and Typhoid Fever Genomics (inc. Host-Pathogen Interaction, Global Health, Enteric Infections)
Our research uses genomic technology to discover how host and pathogen genomic variation is associated with infectious disease outcomes. Our focus is infectious diseases that have high burdens in developing countries and require better tools for their control. Our current work prioritises two, high-burden infectious diseases, TB and typhoid fever. We achieve this by collecting large cohorts of patients for population based studies of human and bacterial genomics. We use phylogenomic analysis of bacterial genomes to understand population structure, transmission, pathogen virulence and drug resistance. We use human genome-wide association studies (GWAS) to identify key mechanisms in the response to disease susceptibility and outcome. Current research projects include:
- DETECT TB will translate advances in sequencing technology to field application by combining clinical metagenomics with robust, portable, low-cost sequencing technology to deliver potent genomic-based diagnostics to resource limited settings.
- TARGET TB aims to understand TB transmission in urbanizing Asia by characterising Mycobacterium tuberculosis pathogen genomic diversity, population structure, transmission dynamics and drug resistance in urban and rural areas of Nepal with high TB burden.
- TB RECOVERY is a project providing nutritional support to our study participants in two districts of Nepal with high TB burden
- Our human genomics studies aim to advance our fundamental understanding of TB and typhoid by discovering genetic variation associated with active disease through genome-wide association studies (GWAS). Additionally in TB, we perform large scale integrative analysis using paired host and pathogen genome profiles to uncover novel aspects of host and pathogen disease biology.
- Dr Sarah Dunstan, Group Leader
- Mr George Tairoa, Research Fellow
- Dr Xuling Chang, Research Fellow
- Ms Pegah Marzooghi, Masters Student (Melbourne)
- 2021 – John Burge Trust (State Trustees) PI, TB RECOVERY: nutritional support for families affected by TB in Nepal
- 2020 – NHMRC Investigator grant, leadership 1 (APP1172853) PI, Genomics to Inform TB Elimination Strategies
- 2019 – National Institute of Health P01 (1P01AI132130-01) co-PI, Systems Genetics of TB
- Dunstan SJ, Williamson DA and Denholm JT. Understanding the global tuberculosis epidemic: moving towards routine whole genome sequencing Int J TB Lung Dis (2019) 23(12): 1241-1242(2) doi.org/10.5588/ijtld.19.0604
- Holt KE, McAdam P, Thai PVK , Ha DTM, Lan NN, Lan NH, Nhu NTQ, Thuong NTT, Thwaites GE, Edwards DJ, Pham K, Farrar JJ, Khor CC, Teo YY, Inouye M, Caws M and Dunstan SJ. Genomic analysis of Mycobacterium tuberculosis reveals complex etiology of tuberculosis in Vietnam including frequent introduction and transmission of Beijing lineage and positive selection for EsxW Beijing variant. (2018) Nature Genetics, Nat Genet, 50:849-856 doi: 10.1038/s41588-018-0117 9
- DunstanSJ and Caws M. Could omics unlock the secret of surviving tuberculous meningitis? Lancet Infectious Diseases. 2018 doi /10.1016/S1473-3099(18)30055-0. Epub 2018 Jan 23.
- 1000 Genomes Project Consortium. A global reference for human genetic variation. (2015) Nature Sep 30;526(7571): 68-74. doi:10.1038/nature15393
- Dunstan SJ, Hue NT, Han B, Li Z, Tram TTB, Sim KS, Parry CM, Chinh NT, Vinh H, Lan NPH, Thieu NTV, Vinh PV, Koirala S, Dongol S, Arjyal A, Karkey A, Shilpakar O, Dolecek C, Foo JN, Phuong LT, Lanh MN, Do T, Aung T, Hon DN, Teo YY, Hibberd ML, Anders KL, Okada Y, Raychaudhuri S, Simmons CP, Baker S , de Bakker PIW, Basnyat B, Hien TT, Farrar JJ, Khor CC. Variation in the HLA-DRB1 region is associated with susceptibility to enteric fever. (2014) Nature Genetics. Dec;46(12):1333-6 doi: 10.1038/ng.3143. Epub 2014 Nov10
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