Dr Rowena Martin – NH&MRC Australian Biomedical Fellow
BSc Hons (ANU), PhD (ANU)

Rowena Martin  is an NH&MRC Biomedical Fellow at the School of Biology, ANU.  She undertook her undergraduate degree at ANU, during which time she worked at CSIRO (Plant Industry;  Forestry and Forest Products) and the NSW Agricultural Research and Veterinary Centre, and was awarded a National Heart Foundation Vacation Scholarship to work on aspects of the endocrinology of pregnancy at the John Hunter Hospital in Newcastle.  She carried out her PhD in the School of Biochemistry and Molecular Biology ANU, taking a multidisciplinary approach to the problem of understanding membrane transport in the malaria parasite.  Her work spanned the fields of cell physiology, biochemistry, bioinformatics, and molecular biology and she was a recipient of the Australian Society of Biochemistry & Molecular Biology ComBio Student Poster Prize for aspects of this research.  In 2005 she took up a postdoc position at the ANU to pursue work she had initiated during her PhD on drug resistance in the malaria parasite, and was awarded the 2007 Early Career Researcher Award of the ARC/NH&MRC Research Network for Parasitology for this research.  In 2008 she was awarded an NH&MRC Australian Biomedical Fellowship, which is to be undertaken at the School of Biology ANU and at the School of Botany, University of Melbourne.

Contact Details

E: Rowena.Martin@anu.edu.au T: (+61 2) 6125 8589 F: (+61 2) 6125 0313

Main Research interests

Membrane transport proteins of the malaria parasite, with an emphasis on those involved in drug resistance and amino acid transport.

Teaching Activities

n/a

Current Research Group

Rosa Marchetti – PhD student Simon Cobbold – PhD student Robert Summers – PhD student Tegan Dolstra  – Honours student Eileen Baker – Research assistant Megan Nash  – Honours student

Former Lab Members

Rachel Slatyer Melanie Bannister-Tyrrell

Research

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, currently accounting for an estimated 5 billion clinical episodes and up to 3 million deaths annually.  An effective vaccine remains elusive and the parasite has developed resistance to most of the antimalarial drugs currently in use.  Chloroquine served as the frontline treatment for malaria over a period of 5 decades and it is estimated that during this time this cheap, safe, and potent antimalarial saved more lives than any other drug in history.  However, the enormous worldwide usage of chloroquine led to the eventual emergence of resistant parasites and the slow but inexorable spread of these strains throughout endemic regions has rendered chloroquine largely ineffectual.  The antimalarials deployed to replace chloroquine have by comparison suffered short life spans. The primary focus of our research group is to characterize the mechanism by which parasites have become resistant to chloroquine.  Resistant parasites accumulate much less chloroquine than do sensitive parasites and this difference is attributed primarily to small changes in a single protein, the “chloroquine resistance transporter” (PfCRT).  However, neither the mechanism by which this protein confers resistance, nor its normal physiological role are understood.  We have succeeded in expressing PfCRT in Xenopus oocytes, achieving a robust and reproducible heterologous system for the study of this protein.  Using this system we have shown that the resistance-conferring form of PfCRT mediates the transport of chloroquine, whereas the wild-type form does not.  We are currently using the PfCRT expression system to explore a number of important aspects of this protein, such as the normal function and physiological role of PfCRT, the effect of different mutations on PfCRT activity, the mechanism by which the compound verapamil reverses resistance, and the interaction of the transporter with different antimalarial drugs. A second key focus of our research is the identification, annotation, and manual curation of membrane transport proteins in the malaria parasite genome. We are also investigating how the parasite obtains nutrients such as amino acids from its host.  This work is being carried out in collaboration with Prof Kiaran Kirk and seeks to characterize parasite’s requirement for, and transport of, amino acids, and to identify the proteins responsible for mediating these transport processes.  A thorough understanding of these mechanisms may provide the basis for novel drug targets and antimalarial strategies.

Publications

2009 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 [PubMed] [Abstract] [Full Text] Martin, R.E., Ginsburg, H. and Kirk, K. (2009) Membrane transport proteins of the malaria parasite. Molec. Microbiol. 74, 519-528 [Wiley] [PubMed] 2007 Henry, R.I., Martin, R.E., Howitt, S.M. and Kirk, K. (2007) Localisation of a candidate anion transporter to the surface of the malaria parasite. Biochem. Biophys. Res. Comm. 363, 288-291. [PubMed] 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, 2217-2224. [Pubmed] 2006 1Saliba, K.J., 1Martin, R.E., Bröer, A., Henry, R.I., McCarthy, C.S., Downie, M.J., Allen, R.J.W., Mullin, K.A., McFadden, G.I., 2Bröer, S.and 2Kirk, K. (2006)  Sodium-dependent uptake of inorganic phosphate by the intracellular malaria parasite.  Nature  443, 582-585. [1,2: Equal contributions] [PubMed] 2005 1Bray, P.G., 1Martin, R.E., Tilley, L., Ward, S.A., Kirk, K. and Fidock, D.A. (2005) Defining the role of PfCRT in P. falciparum chloroquine resistance. Molec. Micro., 56, 323-333 [1: Joint first authors] [PubMed] Kirk, K., Martin, R.E., Bröer, S., Howitt, S.M. and Saliba, K.J. (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. [PubMed] 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 Biology, 6, R26. 2004 Martin, R.E. 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: 1938-1949. [PubMed] 2002 Clements, J.D. and Martin, R.E. (2002) Identification of novel membrane proteins by searching for patterns in hydropathy profiles. European Journal of Biochemistry, 269: 2101-07. [PubMed] 1999 Kirk, K., Staines, H.M., Martin, R.E. and Saliba, K.J. (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. Saliba, K.J., Martin, R.E., Staines, H.M. and Kirk, K. (1999) A novel anion channel in the malaria-infected erythrocyte: opportunities for antimalarial chemotherapy, in Chloride Channels (R.Z. Kozlowski, ed.). Isis Medical Media, pp 137-148.