Center for Infectious Disease Research Pioneers Method for $11.5M Malaria Research Grant
Breakthrough approach overcomes challenges and aims to outsmart drug-resistant parasite
September 20, 2017 (Seattle, Wash.) ― The Center for Infectious Disease Research (CID Research) is part of a new collaboration, a $11.5 million Program Project (P01) grant, to use its breakthrough research method to investigate the genes responsible for drug resistance and virulence in the malaria parasite. The goal is to outsmart drug-resistant malaria and ultimately eliminate the devastating disease.
Ashley Vaughan, Ph.D., Principal Scientist and Stefan Kappe, Ph.D., Professor, at CID Research, are partnering with Michael Ferdig, Ph.D., at the University of Notre Dame and researchers at the Texas Biomedical Research Institute (TBRI) as part of the National Institutes of Health (NIH) funded collaboration.
Above: Ashley Vaughan, Ph.D., Principal Scientist, worked with Stefan Kappe, Ph.D., Professor, to develop a way for malaria parasites to mature in a “chimeric” mouse with a liver consisting of more than 90 percent human cells.
The collaboration brings together experts in distinct fields – systems biology, genomics and global health – to apply modern methods in an attempt to prevent the ongoing crisis of drug-resistant malaria, similar to the drug failure seen in the late 1950s and early 1960s with chloroquine. Malaria, a disease that is preventable and curable, is capable of quickly adapting to resist drug therapies; the widespread use of artemisinin has already led to resistance in Southeast Asia. The spread of artemisinin-resistant malaria to other endemic areas would have a globally devastating impact.
To prevent a global health crisis, this collaboration is set up to take an innovative approach to understand – and hopefully outsmart – drug resistance in the Plasmodium falciparum malaria parasite, using experimental genetic crosses. By crossing one parasite known for drug resistance with one known for drug sensitivity, the researchers can study the genetic offspring and identify the genes associated with drug resistance. This information will help the malaria research community devise better methods to combat the parasite.
Previously, the ability to generate experimental crosses to broadly study the development of drug resistance in P. falciparum – the most lethal of malaria parasites – was hampered by challenges of prohibitive costs, technical difficulty, and ethical dilemmas related to chimpanzee research, which was banned by the NIH in recent years.
CID Research pioneered new methods to overcome many of these challenges, notably developing a way for malaria parasites to develop in a mouse with a liver consisting of more than 90 percent human cells. This “chimeric” mouse replaces a human or chimp as host. This reliable method, combined with systems genetics expertise from the University of Notre Dame and TBRI, now makes it possible to rapidly generate large numbers of parasite progeny for study.
“Our innovative research with human liver-chimeric mice has enabled us to perform genetic crosses with the malaria parasite,” says Vaughan, who optimized this technique in the lab led by Kappe. “This breakthrough will allow us, for the first time, to use systems genetics to gain an understanding of the evolution of drug resistance in this deadly parasite. This will help us combat and control drug resistance."
The research program promises the development of a pipeline for genetic crosses that can revolutionize the response to drug-resistant malaria, putting a new and powerful tool in the hands of researchers around the world working to combat one of the world’s most deadly diseases.
The project is titled “Harnessing The Power of Experimental Genetic Crosses and Systems Genetics to Probe Drug Resistance in Malaria.” In 2015, Vaughan, Kappe and Ferdig, along with Tim Anderson, Ph.D. and Ian Cheeseman, Ph. D., at TBRI, published a paper in Nature Methods that established the proof of concept upon which this new grant award is based.
ABOUT THE CENTER FOR INFECTIOUS DISEASE RESEARCH
The Center for Infectious Disease Research is the largest independent, non-profit organization in the U.S. focused solely on infectious disease research. Our research is the foundation for new drugs, vaccines and diagnostics that benefit those who need our help most: the fourteen million who will otherwise die each year from infectious diseases, including malaria, HIV/AIDS and tuberculosis. Founded in 1976, CID Research partners with key collaborators around the globe and strives to make discoveries that will save lives. For more information, visit www.cidresearch.org.
Notre Dame scientists work to solve gene resistance to malaria drug, WSBT-TV October 2017
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