Malaria: Probing a deadly parasite
7/2/2009
Malaria is the fourth most common cause of all deaths of children under the age of five. Because of the rapid spread of drug resistance to current treatments, new anti-malarial agents are badly needed. Two Discovery Institute investigators have combined their expertise to help find them.
Audrey Odom, MD, PhD, is an infectious disease specialist at St. Louis Children’s Hospital and an instructor of pediatrics at Washington University. As the 2009 Discovery Institute New Faculty Scholar, Odom, who joined the Washington University faculty one year ago, has received partial funding to help establish her laboratory. Her research focuses on enzymes and signaling pathways in the malaria parasite, Plasmodium falciparum, which is the pathogen responsible for most deaths from malaria.
Monita Wilson, PhD, came to Washington University in 1992 as a post-doctoral fellow. She has since become a research assistant professor of medicine, and has published widely in the area of inositol biochemistry. This year,
Wilson received a grant from the Children’s Discovery Institute to apply her expertise to preventing neural tube defects—a common form of birth defect that includes spina bifida.
While Drs. Wilson and Odom pursue very different children’s health issues in their individual research projects, they have joined forces in an investigation that illustrates the Children’s Discovery Institute’s commitment to collaboration.
The tie (or in this case, the molecule) that binds these two investigators is inositol. Inositol is a compound found in the tissues of plants and animals. It plays important roles in molecular pathways that are vital to life.
Dr. Odom is interested in inositol metabolism in the malaria parasite. “Since inositol is essential to so many life-sustaining cellular events in most organisms, understanding its basic forms and roles in the parasite may point to drug targets,” said Odom. “While much is known about inositol in humans and some other organisms, very little is known about how inositol participates in various pathways in the malaria parasite.”
The ultimate goal is to learn if there are inositol dependent pathways to key life-supporting processes in this parasite that are biochemically distinct from human pathways. Finding such distinct molecular pathways will give drug researchers something at which to aim small molecules. The idea is to find a chemical that can shut down the parasite’s unique pathway by inhibiting one or more molecular players within it—thus killing the parasite without affecting the human host.
Recently, thanks to funding from the Children’s Discovery Institute, Dr. Wilson’s expertise in inositol biochemistry and her ability to separate, identify, and quantify inositol-related compounds have been brought to bear on Dr. Odom’s effort to understand signaling pathways in the malaria parasite that may become targets for new anti-malarial agents.
Within her laboratory, Dr. Odom is developing new systems to evaluate essential genes in the malaria parasite, and new approaches for high through-put screening of large libraries of small molecule compounds that may be effective against the parasite.
“Dr. Wilson and I are just beginning to explore inositol metabolism in the malaria parasite,” said Odom. “But, we already know that there are some differences between humans and certain other organisms in the way inositol is synthesized and used, so there is reason to expect that similar distinctions between humans and Plasmodium falciparum may exist.”
Controlling the spread of malaria remains one of the world’s most important issues in children’s health. According to UNICEF, malaria accounts for almost 1 death in 10 worldwide of children under the age of five—and nearly 1 death in 5 in sub-Saharan Africa. New antimalarial agents are urgently needed to replace those to which the parasites have become resistant. Despite certification of malaria eradication in the United States in 1970, 11 outbreaks of probable, locally acquired mosquito transmitted malaria have been reported to the Centers for Disease Control since 1992. Seven cases that occurred in Palm Beach County in Florida in 2003 are a reminder that malaria transmission can resume in the United States.