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Early Career Research
WINNER - Mechanisms of Drug Resistance in the Malaria Parasite
Malaria parasites running on ‘empty'
For over 50 years, chloroquine was been a ‘wonder drug' in the fight against malaria: cheap, safe and highly effective. That was, until recently.
In the late 1990s, scientists observed that the drug was losing potency and it has now been rendered almost useless by the spread of chloroquine-resistant parasites.
Dr Rowena Martin, NH&MRC Australian Biomedical Fellow and Principal Investigator at the Research School of Biology at the Australian National University, has revealed how the parasites have managed to get the upper hand, and what can be done to redress the situation.
For her work uncovering the mechanisms of drug resistance in malaria parasites, Dr Martin has been awarded the inaugural Macquarie University Eureka Prize for Early Career Research.
Malaria infects between 200 and 500 million people every year, killing anywhere from one to three million, mostly children younger than five years of age living in the poorest nations on earth.
Dr Rowena Martin has offered a way forward in malaria treatment through her excellent research and breadth of technical skills, rare in such a young scientist just 35 years of age.
Chloroquine kills malaria parasites by interfering with the digestion of their human host's red blood cells. The drug accumulates in a digestive compartment of the parasite until it reaches toxic concentrations.
In chloroquine-resistant parasites, the drug is unable to accumulate in this compartment and so never reaches the level of concentration required to kill the parasite. It has been known for 10 years that this is due to mutations in a protein called the chloroquine resistance transporter. Dr Martin has shown how the mutant protein protects the parasite from the drug's toxic effects.
While generally thought that the mutant protein was able to transport the drug across membranes, Dr Martin was able to propose a model of how this was done and then develop a series of experiments to demonstrate it.
To do this, she needed to study the protein out of its natural surroundings, and she did it using frogs' eggs. These are simple cells that have been widely used to study membrane transporters in a range of different organisms, however, previous attempts to use the eggs with the mutant protein had failed. Dr Martin believed that this was because when expressed in the eggs, the protein remained inside the cell where it was inaccessible to study.
She managed to genetically modify the mutant protein so that it appeared in high levels on the surface of the frog eggs where she could carry out a detailed analysis.
Dr Martin was the first to demonstrate that the mutant protein, unlike the ‘normal' protein, can actually carry chloroquine across a biological membrane. This means that the parasites with the mutant protein can keep doing their deadly work while the drug is being emptied out of their digestive compartments, where it can do them harm.
Using the same system, Dr Martin has gone on to show that another compound, verapamil, blocks the mutant protein from transporting chloroquine from the digestive compartment, allowing the drug to reach the toxic levels it does in non-resistant parasites.
Her work has opened up two possible paths to future malaria treatment: the development of compounds, such as verapamil, that can be used in combination with chloroquine to render the parasite once again susceptible to the drug; or the development of new drugs that act like chloroquine but bypass the resistance mechanism.
Dr Martin's work has been described as ‘exceptional', ‘truly ground-breaking', and ‘a technical tour de force'.
The $10,000 Eureka Prize for Early Career Research is awarded for outstanding scientific research conducted by an individual or groups of early career researchers who are 35 or younger. It is sponsored by Macquarie University.
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Sponsor
The Macquarie University Eureka Prize for Early Career Research is sponsored by Macquarie University.
Description
The Macquarie University Eureka Prize for Early Career Research is awarded for outstanding scientific research conducted by an individual (or groups) of early career researcher(s) who are 35 years old or younger.
prize
$10,000
Purpose
Macquarie University is home to some of the world's most pre-eminent researchers who attract significant research funding to the University. Our concentrations of research excellence span a wide range of disciplines including Cognitive Science, Lasers and Photonics, Biomolecular Frontiers and Wireless Communications just to name a few.
Macquarie University values, recognises and rewards the significant contribution that young researchers make to their field and to science in Australia.
Judging Criteria
Entries should specifically address how their work meets the following judging criteria:
1. Originality: Describe how your research is original.
2. Scientific Rigour: Describe the scientific rigour of your research, including evidence that the research has undergone peer-review.
3. Potential Impacts: Describe the potential impacts and benefits of your research.
Conditions of entry
The prize is open to individuals or groups.
Individuals entering this prize must be 35 years or younger at the time of close of entries. For a group entry, all members of the group must be 35 years or younger at the time of close of entries.
Individuals may be nominated for their significant role (lead researcher or key researcher) in a group research project, where not all group members are 35 years of age or younger.
Research entered for this prize must have been undertaken:
• in Australia by an Australian citizen(s) or Australian resident(s). Where the entry is by a research group, all members of the group must meet this criterion;
• undertaken no more than 5 years before the closing date for entries.
Entrants may either enter themselves or be nominated by others. If nominating an entrant, please ensure that they have the opportunity to provide input to the documentation provided in support of their nomination.
You must submit an online entry form including all supporting documentation by midnight AEST Friday 7 May 2010 to be eligible for this prize.
Entries with insufficient sets of supporting documentation will not be considered.
Submitted material will not be returned.
Any entries received after midnight AEST Friday 7 May 2010 will not be considered.
Hard-copy applications will not be considered.
The research entered/nominated for this prize may not be entered/nominated for another Australian Museum Eureka Prize.
The deliberations of the judging panel remain confidential. All recommendations and decisions taken are binding and final and no correspondence will be entered into on such matters.
Information provided by the entrant(s) in relation to the Australian Museum Eureka Prizes (including photos), may be used by the Australian Museum for promotional/publicity purposes. This may include, and is not restricted to, the information being used on websites, social media, printed material, advertisements, press releases etc.
Personal information provided in connection with the Australian Museum Eureka Prizes will be used only by the Australian Museum and only in connection with the Australian Museum Eureka Prizes.
How to enter
1. You must prepare and attach the following supporting documents to your online entry form. (Please clearly label your attachments as per below.)a) Research Summary: a brief description of the activity/research entered, including objectives and results to date (two page maximum)
b) Judging Criteria: a brief description of how the entrant's activity/research addresses each of the judging criteria (two page maximum)
c) Published Article: You may, if you wish, include a copy of one published article about the research in an internationally respected journal(s), book(s) or equivalent electronic publications;
d) Assessor Reports: a maximum of four (4) written reports addressing each of the judging criteria from assessors who are familiar with the entrant's work (two page maximum per report). NOTE: Judges rely on assessor's reports to provide additional perspective and informed opinion on entries. Therefore, assessors should not be personally or directly involved in the activity entered in this prize.
Supporting documentation can be uploaded in Microsoft Word (.doc), Adobe Acrobat (.pdf), Microsoft Excel (.xls) or JPeg (.jpg). Collectively, attachments can be no larger than 5MB.
2. Submit an online entry form with your attached supporting documents by midnight AEST Friday 7 May 2010.
If you require further information or help, please call the Australian Museum Eureka Prizes Unit on +61 2 9320 6483 or email eureka@austmus.gov.au
