NIH awards $1.9M grant to Scripps Research scientist for malaria study

Research aims to explore untapped opportunities to combat malaria parasite in liver

A scientist from The Scripps Research Institute has won a four-year, $1.9 million grant from the National Institutes of Health to better understand the parasite that causes malaria, laying the groundwork to develop better drugs to combat the widespread and deadly disease.

"Many antimalarial drugs alleviate symptoms, but do not necessarily result in a complete cure because some malaria parasites are able to persist asymptomatically in the liver for months or years," said Scripps Research Professor Elizabeth Winzeler, who is principal investigator for the new grant. "We hope to find new targets that are critical to the liver stages as well as the blood stages with the long-term aim of designing better drugs."

A Complicated Lifecycle

Malaria is a nasty and often fatal disease, affecting about 250 million people every year in Africa, Asia, and the Americas, according to the World Health Organization (WHO). Each year, more than 1 million people die of malaria, mostly children under the age of five. While significant strides had been made in curtailing the disease, for the last two decades malaria, has again been on the rise due to the emergence of drug-resistant parasites.

The parasite Plasmodium, which causes malaria, has a complicated lifecycle in two hosts-mosquitoes and humans (or other vertebrate). When a malaria-infected mosquito feeds on a person, the parasite enters the human body. Within 30 minutes, the parasite has infected liver cells, where it remains anywhere from eight days to several months without causing noticeable symptoms.

When this period is over, however, the parasite (now in a different form) leaves the liver and enters red blood cells, where it grows and multiplies. When the infected red blood cells eventually burst, the parasite and Plasmodium toxins are released into the bloodstream, and the person feels sick. Symptoms include fever, chills, headache, and other flulike symptoms; in severe cases, patients can experience convulsions, coma, and liver and kidney failure, which can be fatal.

If a mosquito bites the infected person at this point, the parasite will enter the mosquito, where it will continue the cycle by maturing into a form that can infect the next human host.

Untapped Opportunities

Because most antimalarial drugs have targeted the malaria parasite in its blood stages, Winzeler believes there are untapped opportunities to combat the disease in the liver stages of the parasite's lifecycle. That's where the new grant comes in.

The new grant from the NIH National Institute of Allergy and Infectious Diseases will fund research in the Winzeler lab investigating pathways essential to parasite development in both blood and liver stages. Specifically, the lab will look at the development of parasite's resistance to antimalarial compounds in culture. The team will then endeavor to identify and characterize the genetic mutations enabling the drug resistance, providing new information on potential drug targets.

"The work may lead to a better understanding of how to treat tissue-stage malaria, provide new antibiotic resistance genes, and provide information about how eukaryotic pathogens become resistant to drugs," Winzeler said.