Kirk Group - Membrane transport in parasites

Kirk Group with members of the Lehane and van Dooren Groups Kirk Group with members of the Lehane and van Dooren Groups

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.

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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.

Roles of IgM in immunity to malaria in humans

Event | Thu 13 June 2019

A key mediator of protective immunity to malaria is antibodies that block merozoite invasion of the RBC.

Targeting host cell factors as a novel anti-malarial strategy

Event | Thu 11 April 2019

Malaria causes a significant health burden worldwide. An efficient vaccine has yet to be developed but a handful of treatment options exist.

New tools for malaria eradication: integrated packages for geospatial mapping, population-based sampling and high-sensitivity testing

Event | Thu 28 February 2019

Malaria elimination/ eradication has been a global policy for the past decade and has enabled some tremendous achievements.

Characterising a novel family of amino acid transporters in Toxoplasma gondii.

Event | Thu 9 August 2018

Apicomplexans are a phylum of unicellular eukaryotic parasites that cause a range of diseases in humans, including toxoplasmosis and malaria.

Piezo channels: tension, tethers and transduction

Event | Thu 26 July 2018

Mechanosensitive channels are fundamental molecular components of mechanosensory systems in all organisms.

Professor Kiaran Kirk elected Fellow of the Academy of Health and Medical Sciences

Story | Monday 23 October 2017
The Research School of Biology (RSB) welcomes the election of Professor Kiaran Kirk as a Fellow to the Australian Academy of Health and Medical Sciences.

Characterising a new drug target in the malaria parasite

Story | Tuesday 8 August 2017
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

Story | Tuesday 9 May 2017

I have been extremely fortunate in having had very many highly talented people through the lab, and the successes that the lab has had

Beating malaria: All guns to bear

Story | Wednesday 3 June 2015
Groups of scientists across ANU are teaming up to fight one of the world's most deadly diseases.

'Concepts in Parasitology' course

Story | Thursday 18 December 2014
The future of parasite research in Australia will be in safe hands as 16 young Australian scientists converged for an intensive 2-week workshop with world-leading biologists to study worms, protozoans, ticks, fleas, lice and more.

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