Martin Lab - Membrane transport proteins of the malaria parasite

Martin Lab

The malaria parasite is a single-celled microorganism which invades the red blood cells of its host. Malaria remains a major infectious disease in many parts of the world, causing over 200 million cases and 0.5-1.2 million deaths per year. Moreover, malaria imposes horrendous economic burdens upon afflicted countries. An effective vaccine remains elusive and reliance on chemotherapy is under serious threat with the emergence of parasites that are resistant to most, if not all, of the antimalarial drugs available.

We use a combination of biochemistry, chemistry, molecular biology, and bioinformatic techniques to study:

  • Membrane transport proteins of the malaria parasite, with an emphasis on those involved in drug resistance
  • Mechanisms of drug resistance and drug action in the malaria parasite
  • Design of novel antimalarial drugs
 
 
 

Members

Leader

Rowena Martin

Rowena Martin
Rowena Martin carried out her PhD in the School of Biochemistry and Molecular Biology ANU, taking a multidisciplinary approach...

Honours Student

PhB Student

PhD Student

Research Assistant

Projects

Open to students

Publications

All publications

Google Scholar page

Marchetti RV, Lehane AM, Shafik SH, Winterberg M, Martin RE and Kirk K (2015).  A lactate and formate transporter in the intraerythrocytic malaria parasite, Plasmodium falciparum. Nature Communications, 6: Article 6721.  Open access

Kirk K and Martin RE (2015).  Membrane transport in the malaria parasite, in the Encyclopedia of Malaria (P Kremsner & M Hommel chief eds), Springer, pp 1-11.

Bellanca S, Summers RL, Meyrath M, Dave A, Nash MN, Dittmer M, Sanchez CP, Stein WD, Martin RE1, and Lanzer M1 (2014).  Multiple drugs compete for transport via the P. falciparum chloroquine resistance transporter at distinct but interdependent sites.  Journal of Biological Chemistry, 289: 36336-51.  [1: Joint senior authors]  Open access

Teng R1, Lehane AM1, Winterberg M, Shafik SH, Summers RL, Martin RE, van Schalkwyk DA, Junankar PR, Kirk K (2014).  1H NMR metabolite profiles of different strains of Plasmodium falciparumBioscience Reports, 34: art:e00150.  [1: Joint first authors]  Open access

Summers RL1, Dave A1, Dolstra TJ, Bellanca S, Marchetti RV, Nash MN, Richards SN, Goh V, Schenk RL, Stein WD, Kirk K, Sanchez CP, Lanzer M2, and Martin RE2 (2014).  Diverse mutational pathways converge on saturable chloroquine transport via the malaria parasite’s chloroquine resistance transporter.  Proceedings of the National Academy of Sciences USA, 111: E1759-67.  [1, 2: Equal contributions]  Open access

Deane KJ1, Summers RL1, Lehane AM, Martin RE2, and Barrow RA2 (2014).  Chlorpheniramine analogues reverse chloroquine resistance in Plasmodium falciparum by inhibiting PfCRT.  ACS Medicinal Chemistry Letters, 5: 576-81  [1, 2: Equal contributions]

Hrycyna CA1, Summers RL1, Lehane AM1, Pires MM, Namanja H, Bohn K, Kuriakose J, Ferdig M, Henrich PP, Fidock DA, Kirk K, Chmielewski J2, and Martin RE2 (2013). Quinine dimers are potent inhibitors of the Plasmodium falciparum chloroquine resistance transporter and are active against quinoline-resistant P. falciparum.  ACS Chemical Biology, 9:722-30  [1, 2: Equal contributions]  Open access

Gemma S, Camodeca C, Brindisi M, Brogi S, Kukreja G, Kunjir S, Gabellieri E, Lucantoni L, Habluetzel A, Taramelli D, Basilico N, Gualdani R, Tadini-Buoninsegni F, Bartolommei G, Moncelli MR, Martin RE, Summers RL, Lamponi S, Savini L, Fiorini I, Valoti M, Novellino E, Campiani G, and Butini S (2012).  Mimicking the intramolecular hydrogen Bond: synthesis, biological evaluation, and molecular modeling of benzoxazines and quinazolines as potential antimalarial agents.  Journal of Medicinal Chemistry, 55: 10387-10404.

Gemma S, Camodeca C, Sanna Coccone S, Joshi BP, Bernetti M, Moretti V, Brogi S, Bonache MC, Savini L, Taramelli D, Basilico N, Parapini S, Rottmann M, Brun R, Lamponi S, Caccia S, Guiso G, Summers RL, Martin RE, Saponara S, Gorelli B, Novellino E, Campiani G, and Butini S (2012).  Optimization of 4-aminoquinoline/clotrimazole-based hybrid antimalarials: further structure-activity relationships, in vivo studies, and preliminary toxicity profiling.  Journal of Medicinal Chemistry, 55: 6948-67.

Martin RE, Butterworth A, Gardiner D, Kirk K, McCarthy JS, and Skinner-Adams TS (2012).  Saquinavir inhibits the malaria parasite's chloroquine resistance transporter.  Antimicrobial Agents and Chemotherapy, 56: 2283-9.  Open access

Summers, RL, Nash MN, and Martin RE (2012).  Know your enemy: Understanding the role of PfCRT in drug resistance could lead to new antimalarial tactics.  Cellular and Molecular Life Sciences, 69, 1967-95.

Zishiri VK, Joshi MC, Hunter R, Chibale K, Smith PJ, Summers RL, Martin RE, and Egan TJ (2011).  Quinoline antimalarials containing a dibemethin group are active against chloroquine-resistant Plasmodium falciparum and inhibit chloroquine transport via the P. falciparum chloroquine resistance transporter.  Journal of Medicinal Chemistry, 54, 6956-68.

Zishiri VK, Hunter R, Smith PJ, Taylor D, Summers RL, Kirk K, Martin RE, and Egan TJ (2011).  A series of structurally simple chloroquine chemosensitizing dibemethin derivatives that inhibit chloroquine transport by PfCRT.  European Journal of Medicinal Chemistry, 46: 1729-42.

Cobbold SA, Martin RE and Kirk K (2011).  Methionine transport in the malaria parasite, Plasmodium falciparum.  International Journal of Parasitology, 41: 125-135.    

Summers, RL and Martin RE (2010).  Functional characteristics of the malaria parasite’s ‘chloroquine resistance transporter’: implications for chemotherapy.  Virulence, 1, 304-08.  Open access

Martin RE, Ginsburg H and Kirk K (2009).  Membrane transport proteins of the malaria parasite. Molecular Microbiology, 74: 519-528.

Martin RE, Marchetti RV, Cowan AI, Howitt SM, Bröer S, and Kirk K (2009).  Chloroquine transport via the malaria parasite’s ‘Chloroquine Resistance Transporter’.  Science, 325, 1680-82.  Commentaries: (i) Nelson, N (2009) Faculty of 1000, article 1165434a(ii) Sibley, LD (2009) Faculty of 1000, article 1165434b, and (iii) This week in Science (2009) Science, 325: 1596-7.

Martin RE and Kirk K (2007).  Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparumBlood, 109: 2217-24.

Henry RI, Martin RE, Howitt SM and Kirk K (2007).  Localisation of a candidate anion transporter to the surface of the malaria parasite.  Biochem. Biophys. Res. Comm. 363: 288-291.

Saliba KJ1, Martin RE1, Bröer A, Henry RI, McCarthy CS, Downie MJ, Allen RJW, Mullin KA, McFadden GI, Bröer S2, and Kirk K2 (2006).  Na+-dependent uptake of an essential nutrient by the intracellular malaria parasite.  Nature, 443: 582-85.  [1, 2: Equal contributions]  Commentary: Merzendorfer H. (2007) J Exp Biol, 210: v-vi.

Bray PG1, Martin RE1, Tilley L, Ward SA, Kirk K, and Fidock DA (2005).  Defining the role of PfCRT in P. falciparum chloroquine resistance.  Molecular Microbiology, 56: 323-33.  [1: Joint first authors]

Martin RE, Henry RI, Abbey JL, Clements JD, and Kirk K (2005).  The ‘permeome’ of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum.  Genome Biology, 6: R26.  Open access

Kirk K, Martin RE, Bröer S, Howitt SM and Saliba KJ (2005).  Plasmodium Permeomics: Membrane transport proteins in the malaria parasite. Current Topics in Microbiology and Immunology: Malaria (S. Krishna and D. Sullivan, eds), 295: 325-356.

Martin RE and Kirk K (2004).  The malaria parasite's chloroquine resistance transporter is a member of the drug/metabolite transporter superfamily.  Molecular Biology and Evolution, 21: 1938-49.  Commentaries:  (i) Egan TJ. (2004) Drug Discovery Today, 9: 814-815 and (ii) Hughes A. (2004) Faculty of 1000, article 15240840

Clements JD and Martin RE (2002).  Identification of novel membrane proteins by searching for patterns in hydropathy profiles.  FEBS Journal, 269: 2101-07.

Saliba KJ, Martin RE, Staines HM, and Kirk K (1999).  A novel anion channel in the malaria-infected erythrocyte: opportunities for antimalarial chemotherapy, in Chloride Channels (RZ Kozlowski, ed), Isis Medical Media, pp 137‐48.

Kirk K, Staines HM, Martin RE, and Saliba KJ (1999).  Transport properties of the host cell membrane, in Transport and Trafficking in the Malaria‐Infected Erythrocyte, Wiley, Chichester (Novartis Foundation Symposium 226), pp 55‐73.

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Updated:  04 June 2015/Responsible Officer:  Director RSB/Page Contact:  Webmaster RSB