Kirk Group - Membrane transport in parasites

The primary interest of our research group is in membrane transport mechanisms in malaria and toxoplasma parasites. The proteins involved play a key role in parasite biochemistry and physiology and offer significant potential as antiparasitic drug targets.  

Kiaran is not currently taking on students.  All projects are undertaken in collaboration with the labs of Dr Adele Lehane and/or Dr Giel van Dooren and students are encouraged to contact them in relation to potential research projects.

Members

Leader

Kiaran Kirk

Kiaran Kirk carried out his PhD in the Department of Biochemistry at the University of Sydney (1985-1988). In 1989 he went to...

PhD Student

Visiting Fellow

Projects

Publications

Selected publications

  • Lehane, A.M., Dennis, A.S.M., Bray, K.O., Li, D., Rajendran, E., McCoy, J.M., McCarthur, H.M., Winterberg, M., Rahimi, F., Tonkin, C.J., Kirk, K. and van Dooren, G.G. (2019)  Characterization of the ATP4 ion pump in Toxoplasma gondii.  J. Biol. Chem., pii: jbc.RA118.006706. doi: 10.1074/jbc.RA118.006706
  • Parker, K.E.R., Fairweather, S.J., Rajendran E., Blume M., McConville, M.J., Bröer, S., Kirk, K., van Dooren, G.G. (2019) The tyrosine transporter of Toxoplasma gondii is a member of the newly defined apicomplexan amino acid transporter (ApiAT) family. PLoS Pathogens, 15:e1007577. https://doi.org/10.1371/journal.ppat.1007577 
  • Rosling, J.E.O., Ridgway, M.C., Summers, R.L., Kirk, K. and Lehane, A.M., (2018) Biochemical characterization and chemical inhibition of PfATP4-associated Na+-ATPase activity in Plasmodium falciparum membranes.  J. Biol. Chem., 293, 13327-13337
  • Dennis, A.S.M., Rosling, J.E.O., Lehane, A.M. and Kirk, K. (2018) Diverse antimalarials from whole-cell phenotypic screens disrupt malaria parasite ion and volume homeostasis.  Sci. Rep. 8, 8795. doi: 10.1038/s41598-018-26819-1
  • Dennis, A.S.M., Lehane, A.M., Ridgway, M.C., Holleran, J. and Kirk, K. (2018) Cell swelling induced by the antimalarial KAE609 (cipargamin) and other PfATP4-associated antimalarials.  Antimicrob. Agents Chemother.,  62, pii: e00087-18. doi: 10.1128/AAC.00087-18
  • 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
  • Rajendren, E. Hapuarachchi, S.V., Miller, C.M., Fairweather, S.J., Cai, Y., Smith, N.C., Cockburn, I.A., Bröer, S. Kirk, K., van Dooren, G.G. (2017) Novel cationic amino acid transporters play key roles in the survival and transmission of apicomplexan parasites.  Nature Comm.8:14455. doi: 10.1038/ncomms14455
  • Williamson, A.E., Ylioja, P.M., Robertson, M.N., Antonova-Koch, Y., Avery, V., Baell, J., Batchu, H., Batra, S., Burrows,J.N., Bhattacharyya, S., Calderon, F., Charman, S.A., Clark, J., Crespo, B., Dean, M., Debbert, S.L., Delves, M., Dennis, A.S.M., Deroose, F., Duffy, S., Fletcher, S., Giaever, G., Hallyburton, I., Gamo, F-J., Gebbia, M., Guy, R,K., Hungerford, Z., Kirk, K., Lafuente-Monasterio, M.J., Lee, A., Meister, S., Nislow, C., Overington, J.P., Papadatos, G., Patiny, L., Pham, J., Ralph, S., Andrea Ruecker, A., Ryan, E., Southan, C., Srivastava, K., Swain, C., Tarnowski, M.J., Thomson, P., Turner, P., Wallace, I.M., Wells, T.N.C., White, K., White, L., Willis, P., Winzeler, E.A., Wittlin, S. and Todd, M.H. (2016) Open source drug discovery - Highly potent antimalarial compounds derived from the Tres Cantos arylpyrroles.  ACS Central Science4, e06416. doi: 10.7554/eLife.06416
  • Van Voorhis, W.C. … Kirk, K. … Lehane A.M. … [188 authors in total] (2016) Open source drug discovery with the Malaria Box compound collection for neglected diseases and beyond. PLoS Pathog 12: e1005763. doi:10.1371/journal.ppat.1005763
  • Tran, P.N., Tate, C.J., Ridgway, M.C., Saliba, K.J., Kirk, K. and Maier, A.G. (2016) Human dihydrofolate reductase influences the sensitivity of the malaria parasite Plasmodium falciparum to ketotifen - A cautionary tale in screening transgenic parasites.  International Journal for Parasitology: Drugs and Drug Resistance.  6, 179-183
  • Winterberg, M. and Kirk, K. (2016) A high-sensitivity HPLC assay for measuring intracellular Na+ and K+ and its application to Plasmodium falciparum infected erythrocytes. Sci. Rep. 6, 29241; doi: 10.1038/srep29241
  • Cobbold, S.A., Llinas, M. and Kirk, K. (2016) Sequestration and metabolism of host cell arginine by the intraerythrocytic malaria parasite Plasmodium falciparumCellular Microbiol.  18, 820-830
  • Kirk, K. (2015) Ion regulation in the malaria parasite. Annu. Rev. Microbiol. 69, 341–59
  • Spillman, N.J. and Kirk, K. (2015) The malaria parasite cation ATPase PfATP4 and its role in the mechanism of action of a new arsenal of antimalarial drugs. Int.J. Parasitol.: Drugs and Drug Resistance. 5, 149-162
  • 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
  • Jiménez-Díaz, M.B., Ebert, D., Salinas, Y., Pradhan, A., Lehane, A.M., Myrand-Lapierre, M., O’Loughlin, K.G., Shackleford, D.M., de Almeida, M.J.L., Carillo, A., Clark, J., Dennis, A.S.M., Diep, J., Deng, X., Duffy, S., Endsley, A.N., Guiguemde, G.F.A., Gomez-Lorenzo, M.G., Holbrook, G., Horst, J., Kim, C., Liu, J., Lee, M.C.S., Matheny, A., Martínez, M.S., Miller, G., Rodriguez-Alejandre, A., Sanz, L., Sigal, M., Spillman, N.J., Stein, P.D., Wang, Z., Zhu, F.,, Waterson, D., Knapp, S., Shelat, A.A., Fidock, D.A., Gamo, F.J., Charman, S.A., Mirsalis, J.C., Ma, H., Ferrer, S., Kirk, K., Angulo-Barturen, I., Kyle, D.E., DeRisi, J.L., Floyd, D.M., Guy, R.K. (2014) (+)-SJ733: A Clinical Candidate for Malaria that Acts Through ATP4 to Induce Rapid Host-Mediated Clearance of Plasmodium. Proc. Natl Acad. Sci. USA.111, E5455- E5462
  • Vaidya, A.B., Morrisey , J.M., Zhang, Z., Das, S., Daly, T.M., Otto, T.D., Spillman, N.J., Wyvratt, M., Siegl, P., Marfurt, J., Wirjanata, G., Sebayang, B., Price, R.N., Chatterjee, A., Nagle, A., Stasiak, M., Charman, S.A., Angulo-Barturen, I., Ferrer, S., Jiménez-Díaz, M.B., Martínez, M.S., Gamo, F.J., Avery, V.M., Ruecker, A., Delves, M., Kirk, K., Berriman, M., Kortagere, S., Burrows, J., Fan, E. and Bergman, L.W. (2014) Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum.  Nature Comm.  5, 5521
  • Spillman, N.J., Allen, R.J.W., McNamara, C.W., Yeung, B.K.S., Winzeler, E.A., Diagana, T.T. and Kirk, K. (2013) Na+ regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials. Cell Host & Microbe 13, 227-237
  • 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
  • Martin, R.E., Marchetti, R.V., Cowan, A.I., Howitt, S.M., Bröer, S. and Kirk, K. (2009) Chloroquine transport via the malaria parasite’s ‘Chloroquine Resistance Transporter’. Science, 325, 1680-1682
  • Dean, S., Marchetti, R., Kirk, K. and Matthews, K.R. (2009) A surface transporter family conveys the differentiation signal in African trypanosomes. Nature, 459, 213-217
  • Lehane, A.M., Hayward, R., Saliba K.J. and Kirk, K. (2008) A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine-resistant malaria parasites. J. Cell Sci. 121, 1624-1632
  • Martin, R.E. and Kirk, K. (2007) Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Blood 109, 2219-2226
  • Salibaa, K.J., Martina, R.E., Bröer, A., Henry, R.I., McCarthy, C.S., Downie, M.J., Allen, R.J.W., Mullin, K.A., McFadden, G.I., Bröerb, S. and Kirkb, K. (2006) Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite. Nature 443, 582-585 [a,b Equal contributions]
  • Martin, R.E., Henry, R.I., Abbey, J.L., Clements, J.D, and Kirk, K. (2005) The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum. Genome Biol. 6, R26
  • Martin, R.E. and Kirk, K. (2004) The malaria parasite’s chloroquine resistance transporter is a member of the drug/metabolite transporter superfamily. Mol. Biol. Evol. 21, 1938–1949
  • Allen, R.J.W. and Kirk, K. (2004) The membrane potential of the intraerythrocytic malaria parasite, Plasmodium falciparum. J. Biol. Chem., 279, 11264-11272
  • Kirk, K. (2001) Membrane transport in the malaria-infected erythrocyte. Physiol. Rev. 81, 495-537
  • Reed, M.B., Saliba, K.J., Caruana, S.R., Kirk, K. and Cowman, A.F. (2000) Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403, 906-909.

News & events

News

ARC logo
17
Nov
2014
The School has done very well with regards to Discovery projects and DECRA fellowships. Congratulations to all successful applicants.
Dr Phuong Tran at the ANU Research School of Biology. Photo: Stuart Hay, ANU
09
Sep
2014
A new study has revealed a weak spot in the complex life cycle of malaria, which could be exploited to prevent the spread of the deadly disease.
Professor Kiaran Kirk
30
Apr
2014
Professor Kiaran Kirk has been appointed as the Dean of the ANU College of Medicine, Biology and Environment.
Mosquito. Photo: John Tann
14
Feb
2013
Researchers have discovered how a new class of antimalarial drugs kills the malaria parasite, showing that the drugs block a pump at the parasite surface, causing it to fill with salt.

Pages

Highlights

Characterising a new drug target in the malaria parasite

Malaria remains a serious global health threat, with up to half of the world’s population living in malaria endemic regions. Although significant advances in malaria control have been made in the past few decades, resistance to our current antimalarial drug repertoire threatens control efforts.

Kiaran Kirk, BSB, and College of Science Dean

My research group is run jointly with Adele Lehane, who is a DECRA Fellow and who takes the lead role in much of what we do.

Updated:  21 May 2019/Responsible Officer:  Director RSB/Page Contact:  Webmaster RSB