Malaria is a life-threatening infectious disease caused by Plasmodium – a single-celled parasite that invades our bodies and hijacks oxygen-carrying red blood cells. Once inside these cells, Plasmodium feeds on haemoglobin molecules and replicates itself many times over. The parasites then burst out – only to invade more red blood cells.
This cyclical process can produce billions of parasites in an infected person and these numbers must be brought under control to prevent or cure severe malaria symptoms.
Our lab staff focus on understanding how Plasmodium parasites and the body’s immune system interact with each other. Our approach is highly collaborative – we combine our expertise in experimental models of malaria with researchers around the globe who are world-leaders in the areas of experimental immunology, mathematical modelling, single-cell genomics, computational biology and parasite genetics. Through this network, we explore host/parasite interactions in vivo by combining high-throughput technologies, systems biology approaches and state-of-the-art quantitative methods.
Most importantly, we provide an intellectually creative, vigorous and enjoyable training environment for the next generation of biomedical researchers. We welcome interest from prospective Honours, Masters, and PhD students.
After tracking individual malaria parasites as they matured and ruptured out of one red blood cell and invaded a number of others, we then employed mathematical modelling techniques to reveal that the body can in fact slow down parasite maturation in vivo. Proceedings of the National Academy of Sciences (USA) 2017: “Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection” http://www.pnas.org/content/114/29/7701.long
Using single-cell RNA-seq and computational modelling, we described how CD4+ T cells ‘choose’ between Th1 and Tfh fates in vivo. Science Immunology, 2017: Single-cell RNA-seq and computational analysis using temporal mixture modeling resolves TH1/TFH fate bifurcation in malaria (View full free text article here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365145/ and the database here: www.plasmoTH.org)We found that ICOS-dependent humoral immune responses, including Tfh cell differentiation and antibody production, were impaired by Type I Interferon-signalling. PLoS Pathogens, 2016: IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium InfectionWe found that Type I Interferon-signalling in splenic CD8- dendritic cells hindered Th1 responses in vivo. Journal of Clinical Investigation, 2014: Type I IFN signaling in CD8– DCs impairs Th1-dependent malaria immunity
Kylie R. James, Megan S. F. Soon, Ismail Sebina, Daniel Fernandez-Ruiz, Gayle Davey, Urijah N. Liligeto, Arya Sheela Nair, Lily G. Fogg, Chelsea L. Edwards, Shannon E. Best, Lianne I. M. Lansink, Kate Schroder, Jane A. C. Wilson, Rebecca Austin, Andreas Suhrbier, Steven W. Lane, Geoffrey R. Hill, Christian R. Engwerda, William R. Heath and Ashraful Haque. IFN Regulatory Factor 3 Balances Th1 and T Follicular Helper Immunity during Nonlethal Blood-Stage Plasmodium Infection J Immunol January 10, 2018, ji1700782; DOI: https://doi.org/10.4049/jimmunol.1700782
Lönnberg T, Svensson V, James KR, Fernandez-Ruiz D, Sebina I, Montandon R, Soon MSF, Fogg LG, Sheela Nair A, Liligeto U, Stubbington MJT, Ly L, Otzen Bagger F, Zwiessele M, Lawrence ND, Souza-Fonseca-Guimaraes F, Bunn PT, Engwerda CR, Heath WR, Billker O, Stegle O*, Haque A*, Teichmann SA* (* Co-Senior) Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves Th1/Tfh fate bifurcation in malaria Science Immunology 2017 Mar 3;2(9). pii: eaal2192. doi: 10.1126/sciimmunol.aal2192.
Khoury DS, Cromer D, Akter J, Sebina I, Elliott T, Thomas BS, Soon MSF, James KR, Best SE, Haque A*, Davenport MP* (* Co-senior) Host-mediated impairment of parasite maturation during blood-stage Plasmodium infection Proc Natl Acad Sci USA (Accepted 3 July 2017)
Sebina I, James KR, Soon MSF, Fogg LG, Best SE, de Labastida Rivera F, Montes de Oca M, Amante FH, Thomas BS, Beattie L, Souza-Fonseca-Guimaraes F, Smyth MJ, Hertzog PJ, Hill GR, Hutloff A, Engwerda CR, Haque A. IFNAR1-signalling obstructs ICOS-mediated humoral immunity during non-lethal blood-stage Plasmodium PLoS Pathogens 2016 12 (11), e1005999. Published 3 Nov 2016
Edwards CL, Best SE, Gun SY, Claser C, JamesKR, Montes de Oca M, Sebina I, de Labastida Rivera F, Amante FH, Hertzog PJ, Engwerda CR, Renia L & Haque A. Spatio-temporal requirements for IRF7 in mediating type I IFN-dependent susceptibility to blood-stage Plasmodium infection Eur J Immunol 2015 Jan;45(1):130-41. doi: 10.1002/eji.201444824.
Haque A, Best SE, Montes de Oca M, James KR, Ammerdorffer A, Edwards CL, de Labastida Rivera F, Amante FH, Bunn PT, Sheel M, Hertzog PJ, Kalinke U, MacDonald KPA, Hill GR, Engwerda CR. Type I IFN signalling in CD8- DC impairs Th1-dependent malaria immunity. J Clin Invest 2014 (124: 2483-2496).
Group Leader: Associate Professor Ashraful Haque
- Jessica Engel, Postdoctoral scientist
- Josh Lee, Postdoctoral scientist
- Arya SheelaNair, Research assistant
- Megan Soon, PhD student
- Jasmin Akter, PhD student
- Lianne Lansink, PhD student
- Clara Pernold, Visiting student
- Aleksandra Romanczuk, Visiting student
- Pawat Laohamonthonkul, Honours student
- Using Parasite mRNA-sequencing and mathematical modelling to study how Plasmodium responds to the host in vivo
- Using single-cell transcriptomics to study T cell responses in the gut during Graft-versus Host Disease
- Using single-cell transcriptomics and epigenomics to study CD4+ T cell memory in experimental malaria
- Using bioinformatics to examine differential gene splicing at single-cell level
- Using high-throughput gene editing techniques to examine CD4+ T cell responses in vivo during experimental malaria
If you wish to apply for QIMR Berghofer's student program,
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