The malaria parasite has an active metabolism, importing nutrients, exporting metabolic wastes and generating a wide range of metabolic intermediates. We are using a combination of genetic, physiological and metabolomic approaches to understand the different processes, pathways and proteins involved, with the long term aim of identifying nutrient and metabolite transporters that are sufficiently different from those in humans to allow them to be exploited as antimalarial drug targets.
Recent work in this area has focused on:
1. A novel family of transporters - the 'Novel Putative Transporters' or NPTs (Martin et al. (2005) Genome Biology 6, R26) - one member of which has been implicated in the survival of the transmissable (gametocyte) form of the rodent malaria parasite, Plasmodium berghei (Baldacci et al. (2011) Molec. Microbiol. 81, 1343-57). Work on this project is done in collaboration with Giel van Dooren and Stefan Bröer (Research School of Biology) and involves experiments on both Plasmodium falciparum and P. berghei (in collaboration with Ian Cockburn at the John Curtin School of Medical Research), and on the related human pathogen Toxoplasma gondii.
Students interested in working on this research project should contact Dr Giel van Dooren.
2. Members of the Formate-Nitrite Transporter (FNT) family, one of which has been implicated in the export of lactic acid from the intraerythrocytic malaria parasite (Wu et al. (2015) Nature Comm. 6, 6284; Marchetti et al. (2015) Nature Comm. 6, 6721).
Students interested in working on this research project should contact Dr Adele Lehane.
Recent papers on nutrient/metabolite transporters in the malaria parasite
- Hapuarachchi, S.V., Cobbold, S.A., Shafik, S.H., Dennis, A.S.M., McConville, M.J., Martin, R.E., Kirk, K.*, Lehane, A.M.* (2017) The malaria parasite’s lactate transporter PfFNT is the target of antiplasmodial compounds identified in whole cell phenotypic screens. PLoS Pathog., 13:e1006180. doi: 10.1371/journal.ppat.1006180 [*Joint Senior & Corresponding Authors]
- Rajendren, E. Hapuarachchi, S.V., Miller, C.M., Fairweather, S.J., Cai, Y., Smith, N.C., Cockburn, I.A., Bröer, S. Kirk, K.* and van Dooren, G.G.* (2017) Cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites. Nature Comm., 8:14455. doi: 10.1038/ncomms14455 [*Joint Senior & Corresponding Authors]
- Cobbold, S.A., Llinas, M. and Kirk, K. (2016) Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasite Plasmodium falciparum. Cellular Microbiol. 18, 820-830
- Marchetti, R.V., Lehane, A.M., Shafik, S.H., Winterberg, M., Martin, R.E. and Kirk, K. (2015) A lactate and formate transporter in the intraerythrocytic malaria parasite, Plasmodium falciparum. Nature Comm. 6, 6721
- Teng, R., Lehane, A.M., Winterberg, M., Shafik, S.H., Summers, R.L., Martin, R.E., van Schalkwyk, D.A., Junankar, P.R. and Kirk, K. (2014) 1H NMR metabolite profiles of different strains of Plasmodium falciparum. Bioscience Reports. 34, 685-699
- Tran, P., Brown, S., Mitchell, T., Matuschewski, K., McMillan, P., Kirk, K., Dixon, M. and Maier, A. (2014) A female-gametocyte-specific ABC transporter plays a role in lipid metabolism in the malaria parasite. Nature Comm. 5, 4773
- Kirk, K. and Lehane, A.M. (2014) Membrane transport in the malaria parasite and its host erythrocyte. Biochem. J. 457, 1-18
- Barrand, M.A., Winterberg, M., Ng, F., Nguyen, M., Kirk, K. and Hladky, S.B. (2012) Glutathione export from human erythrocytes and Plasmodium falciparum malaria parasites. Biochem. J. 448, 389-400
- Winterberg, M., Rajendran, E., Baumeister, S., Bietz, S., Kirk, K. and Lingelbach, K. (2012) Chemical activation of a high-affinity glutamate transporter in human erythrocytes and its implications for malaria-parasite induced glutamate uptake. Blood 119, 3604-3612
- Niemand, J., Louw, A.I., Birkholtz, L. and Kirk, K. (2012) Polyamine uptake by the intraerythrocytic malaria parasite, Plasmodium falciparum. Int. J. Parasitol. 42, 921-929
- Cobbold, S.A., Martin, R.E. and Kirk, K. (2011) Methionine transport in the malaria parasite, Plasmodium falciparum. Int. J. Parasitol. 41, 125-35
- Downie, M.J., El Bissati, K., Bobenchik, A.M., Lochlainn, L.N., Amerik, A., Zufferey, R., Kirk, K. and Ben Mamoun, C. (2010) PfNT2: a permease of the equilibrative nucleoside transporter family in the endoplasmic reticulum of Plasmodium falciparum. J. Biol. Chem. 285, 20827-33
- Teng, R., Junankar, P.R., Bubb, W.A., Rae, C., Mercier, P. and Kirk, K. (2009) Metabolite profiling of the intraerythrocytic malaria parasite Plasmodium falciparum by 1H NMR spectroscopy. NMR in Biomedicine 22, 292-302
- Kirk, K., Howitt, S.M., Bröer. S., Saliba, K.J. and Downie, M.J. (2009) Purine uptake in Plasmodium: transport versus metabolism. Trends in Parasitology 25, 246-9
- Martin, R.E., Ginsburg, H. and Kirk, K. (2009) Membrane transport proteins of the malaria parasite. Molec. Microbiol. 74, 519-28
- Downie, M.J., Saliba, K.J., Bröer, S., Howitt, S.M. and Kirk, K. (2008) Purine nucleobase transport in the intraerythrocytic malaria parasite. Int. J. Parasitol. 38, 203-9
- Downie, M.J., Kirk, K. and Ben Mamoun, C. (2008) Purine salvage pathways in the intraerythrocytic malaria parasite. Eukaryotic Cell 7, 1231-7.