Fighting back against malaria

Rowena Martin

The Australian National University, Canberra/The University of Melbourne

Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)
Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)

In the 1950s it seemed as if medical science was winning the fight against malaria with the help of the ‘wonder drug’ chloroquine. Over the past half century the drug has saved hundreds of millions of lives.

But now the parasite that causes malaria has fought back. Chloroquine-resistant malaria has become common in developing countries. Rowena Martin is working to understand what happened, and to develop new ways of treating malaria.

In a series of discoveries, Rowena and her colleagues at the Australian National University (ANU) have revealed some of the biochemical tricks the malaria parasite uses. Now she is honing ways that chloroquine-based drugs can be altered to give them a new lease of life.

Rowena’s achievements have won her a $20,000 L’Oréal Australia For Women in Science Fellowship which she will use to study the complex biochemistry that gives rise to resistance.

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At secondary school Rowena had broad interests ranging from science to architecture. But during her undergraduate degree at university she was given several opportunities to work in research labs – and she was hooked. “I really love the problem solving, lateral thinking, and creativity involved in scientific research. And the excitement when you make the big discovery in the small hours of the morning. It’s a great feeling.”

It wasn’t until working on her Honours project that she learned that the ancient scourge of malaria was on the march again. This year it will infect about 300 million people and kill about a million of them.

But that’s just one part of the problem, according to Rowena. “Malaria places an immense economic burden on a country. It isn’t just associated with poverty, it is a cause of poverty,” she says.

“The parasite’s ability to develop resistance to drugs appears to be inexhaustible, so we constantly need to look for novel compounds and new ways to use the existing ones.”

Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)
Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)

The parasite enters our bodies when we’re bitten by an infected mosquito. It eventually invades and plunders our red blood cells, consuming the haemoglobin contained within. The digestion of haemoglobin, which takes place in the parasite’s stomach compartment, releases the iron-containing, non-protein component, haem. Free haem is toxic to the parasite, which responds by converting it to a harmless crystal. Chloroquine works by blocking the formation of these crystals, and the parasite is poisoned by the haem it has released.

Ten years ago researchers discovered that just a few small changes in one protein, PfCRT, were enough to give the parasite resistance to chloroquine. But they didn’t know what the changes did. That’s been the focus of Rowena’s contribution.

First, she developed a system to study PfCRT in frog eggs – allowing her to examine it in isolation and in detail. That led to a critical discovery. “We found how the protein acts in the drug-resistant parasite. It moves chloroquine out of the parasite’s stomach compartment so that the drug can’t accumulate at its site of action.”

That research was published in the journal Science in 2009. Now Rowena is working to refine the details of the process, and to understand what the role of this protein is in normal parasites.

“The L’Oréal Fellowship is a great honour. The money will help me develop my career as an independent researcher and build my research team. We will be using new tools such as metabolomics to investigate the normal function of the PfCRT protein and how to inhibit it.”

Qualifications

2005 – PhD (Biochemistry, cell physiology, molecular biology, and bioinformatics), TheAustralian National University (ANU)

1997 – Bachelor of Science with Honours (Biochemistry and cell physiology), ANU

Career highlights, awards, fellowships, grants

2010 – Australian Museum Eureka Prize Finalist for Early Career Research

2009-2012 – National Health and Medical Research Council Australian Biomedical Fellowship

2008-present – Principal investigator, Research School of Biology, ANU and the School of Botany, University of Melbourne

2008-2010 – National Health and Medical Research Council project grant: Characterization of the chloroquine resistance transporter of the malaria parasite

2007 – ASP & Australian Research Council/National Health and Medical Research Council Parasitology Network Early Career Researcher Award

2005 – Australian Research Council Research Associate, School of Biochemistry and Molecular Biology, ANU

2001 – Australian Society of Biochemistry and Molecular Biology ComBio Student Poster Prize

1998 – Australian Postgraduate Award

1996 – Research assistant, CSIRO Division of Forestry and Forestry Products, Canberra

1996 – Maternal Health Research Scholarship

1995 – Research assistant, New South Wales Agricultural Research and Veterinary Centre, Orange

1995 – National Heart Foundation Vacation Scholarship

1994 – Research Assistant, CSIRO Division of Plant Industry, Canberra

Research highlights

  • More than ten presentations at Australian and international conferences and institutions including three invited conference and seminar presentations
  • Thirteen publications including six first-author journal articles, three reviews and two book chapters
  • A first-author paper in Science and a co-first-author paper in Nature
  • Actively involved in editorial and peer review for a variety of journals and grants
  • Currently supervising several PhD and Honours students

Top five publications

Martin RE (corresponding author), Marchetti RV, Cowan AI, Howitt SM, Broer S, and Kirk K. (2009) Chloroquine transport via the malaria parasite’s ‘Chloroquine resistance transporter’. Science, 325, 1680-82. (IF = 29.747; 7 cites)

Saliba KJ (co-first author), Martin RE (co-first author), Broer A, Henry RI, McCarthy CS, Downie MJ, Allen RJW, Mullin KA, McFadden GI, Broer S, and Kirk K. (2006) Na+-dependent uptake of an essential nutrient by the intracellular malaria parasite. Nature, 443: 582-85. (IF = 34.48; 23 cites)

Martin RE and Kirk K. (2007) Transport of the essential nutrient isoleucine in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Blood, 109: 2217-24. (IF = 10.555; 19 cites)

Martin RE and Kirk K. (2004) The malaria parasite’s chloroquine resistance transporter is a member of the drug/metabolite transporter superfamily. Mol. Biol. Evol., 21: 1938-49. (IF = 9.872; 66 cites)

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 Biol., 6: R26. (IF = 6.626; 52 cites)

Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)
Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)
Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)
Rowena Martin, The Australian National University, Canberra/The University of Melbourne (credit: L’Oréal Australia/sdpmedia.com.au)