Leann Tilley laboratory
Professor Leann Tilley
+61 3 8344 2227
As part of her Australian Laureate Fellowship Program, with funding from the Australian Research Council, Professor Tilley created the Georgina Sweet Award for Women in Quantitative Bioscience. For further details:
Malaria parasite-infected erythrocytes
Every minute, one child in Africa dies from malaria. Around the world, the mosquito-borne parasite kills about 450,000 people each year, most of them children and pregnant women, while another 200 million people suffer illness as a result of malaria infections.
Carried by the Anopheles mosquito, the tiny malaria parasite invades the victim's red blood cells where it starts devouring the red cell haemoglobin and changing the cells so that the infected red blood cells stick to blood vessel walls. This leads to the typical symptoms of fever and headaches, but in severe cases results in coma and death.
Electron tomography of the malaria parasite, P. falciparum. The rendered models show different stages of development of the parasite in its host, a red blood cell.
The Tilley lab is working as part of a global effort to understand and control malaria. We undertake research in the areas of cell biology and drug development related to the malaria parasite, Plasmodium falciparum. We are particularly interested in in designing antimalarial drugs, based on inhibition of protein translation. We are interested in how the parasite alters the erythrocyte surface to cause malaria pathology, as well as the remarkable transformation that turns parasites banana-shaped and allows them to be transmitted from a human host to a mosquito vector.
Stanley (Cheng) Xie
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- Yang, T., Yeoh, L., Tutor, M., Dixon, M.W., McMillan, P.J., Xie, S.C., Bridgford, J.L., Gillett, D.L., Duffy, M., McConville, M.J., Ralph, S.A., Tilley, L., Cobbold, S.A., (2019) Decreased K13 abundance reduces haemoglobin catabolism and proteotoxic stress, underpinning artemisinin resistance. â€ Equal contribution Cell Reports 29, 2917-2928
- Xie, S.C.^, Metcalfe, R.^, Hanssen, E.^, Yang, T., Gillett, D.L., Leis, A.P., Morton, C.J., Kuiper, M., Parker, M.W., Spillman, N.J., Wong, W., Tsu, C., Dick, L.R., Griffin, M.D.W.* and Tilley, L.* (2019) The structure of the PA28/20S proteasome complex from Plasmodium falciparum and implications for proteostasis. Nature Microbiology 4(11):1990-2000. IF: 14.174. ^*Equal contribution.
- Bridgford, J.L., Xie, S.C., Cobbold, S.A., Pasaje, C.F.A., Herrmann, S., Yang, T., Gillett, D.L., Dick, L.R., Ralph, S.A., Dogovski, C., Spillman, N.J. and Tilley, L. (2018) Artemisinin kills malaria parasites by unfolding proteins and inhibiting the proteasome. Nature Communications 9, 3801. IF: 12.124
- Batinovic, S., McHugh, E., Chisolm, S., Liu, B., Dumont, L., Charnaud, S.C., Matthews, K., Gilson, P.R., McMillan, P.J., de Koning Ward, T.F., Dixon M.W.A. and Tilley, L. (2017) An Exported Protein-Interacting Complex involved in the trafficking of virulence determinants in Plasmodium-infected erythrocytes. Nature Communications 8: 16044.
- Li, H., O'zDonoghue, A., van der Linden, W. A., Xie, S. C., Tilley, L., Craik, C. S., C. A. da Fonseca, P. and Bogyo, M. (2016) Structure and function based design of Plasmodium-selective proteasome inhibitors. Nature 530, 233-236.
- Dearnley, M.K., Trang, C.T.T., Zhang, Y., Looker, O., Huang, C., Klonis, N., Yeoman, J., Kenny, S., Arora, M., Osborne, J., Chandramohanadas, R., Zhang, S., Dixon, M.W.A. and Tilley, L. (2016) Host cell remodelling in sexual blood stages of the malaria parasite, Plasmodium falciparum. Proc. Natl. Acad. Sci. USA 113(17):4800-5.
- Dogovski, C., Xie, S.C., Burgio, G., Bridgford, J., Mok, S., McCaw, J., Chotivanich, K., Kenny, S., GnÃ¤dig, N., Straimer, J., Bozdech, Z., Fidock, D.A., Simpson, J.A., Dondorp, A.M., Foote, S., Klonis, N., Tilley, L. (2015) Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance. PLoS Biology 13(4): e1002132.
- Klonis, N., Xie, S.C., McCaw, J., Crespo, M., Zaloumis, S., Simpson, J., Tilley, L. (2013) Altered temporal response of malaria parasites determines differential sensitivity to artemisinin. Proc. Natl. Acad. Sci. USA 110:5157-62.
- Klonis N, Crespo M, Abu-Bakar N, Bottova I, Kenny S, Rosenthal P, Tilley, L (2011) Artemisinin action against Plasmodium falciparum requires hemoglobin uptake and digestion. Proc. Natl. Acad. Sci. USA 108:11405-10.
- Abu-Bakar, N., Klonis, N., Hanssen, E., Chan, C. and Tilley, L. (2010) Digestive vacuole genesis and endocytic processes in the early intraerythrocytic stages of Plasmodium falciparum. Journal of Cell Science 123, 441-450.
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For further information about this research, please contact Head of Laboratory, Redmond Barry Distinguished Professor of Biochemistry & Pharmacology, ARC Australian Laureate Fellow (2015-2020) Professor Leann Tilley
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