Virginia Tech Scientist Seek Genetic Solution To Malaria

October 30, 1998

BLACKSBURG, Va., Oct. 30, 1998 -- Malaria, a parasitic disease transmitted by mosquitoes to humans and animals, has made such a dramatic re-emergence in many areas of the world that the last five years has seen the growth of global interest in finding novel strategies to control the disease. Somewhere in the workings of the genes of mosquitoes may be a key to disrupting the insect's complex relationship with the parasites, a key that could break the cycle of transmission.

Shirley Luckhart, an assistant professor of biochemistry at Virginia Tech, is searching for that key. She's studying the two-week period when the malaria parasite develops inside a mosquito.

Only about 70 of the hundreds of mosquito species are capable of transmitting malaria. The disease-causing parasites must negotiate a torturous life cycle that alternates between the mosquito and an animal host. Parasites are ingested by a susceptible mosquito as it sucks blood from an infected host.

The parasite must then mature and reproduce during a two-week period in the mosquito, creating a new generation of parasites which are injected into another host when the mosquito feeds again.

Luckhart said that resistant parasites have emerged for each of the eight drugs that are commercially available to treat malaria. The species of mosquitoes that carry malaria are also becoming resistant to a number of control methods.

Countries witnessing a rising incidence of the disease are often experiencing dissolving social structures, which leads to increasingly ineffective control measures.

"The approach we're taking, if it's successful, is to develop transgenic mosquitoes that are incapable of transmitting the parasite," she said. "We're really at the beginning of a three-step process. First we need to identify candidate genes that affect the life cycle of the parasite. Then we need to develop strategies to manipulate the gene and to introduce the modified gene into a population of mosquitoes."

Luckhart is looking at biological and biochemical events occurring in the mosquito and in the parasite during the two-week incubation period.

"What we want to do is identify points in that process where the mosquito's immune system keeps the parasite's development in check," Luckhart said. "We've discovered recently that the immune response of mosquitoes involves the production of nitric oxide; humans also produce nitric oxide in response to malaria infection."

The toxic nitric oxide kills some of the parasites in the mosquito, but by the time it is produced the parasite has multiplied sufficiently to ensure that some individuals will survive.

"There's a limit to the amount of nitric oxide that can be produced," Luckhart said. "It's an incredibly toxic substance. Uncontrolled, it's a suicide response because it's so toxic that it would kill the mosquito.

"We may be able to enhance the production of mosquito nitric oxide, or we may be able to change it's timing," she said. "If we can trigger the release of nitric oxide sooner in the process, we may be able to eliminate the parasite before it has established itself."

The gene for the enzyme responsible for nitric oxide production in mosquitoes is very similar to the same gene in humans. Luckhart is looking at what drives nitric oxide production, such as the signaling that turns on the gene in mosquitoes.

"We've completed characterizing the gene," Luckhart said. "We're just starting to characterize it's regulatory aspects. There's a great deal of work yet to come."

There is also the possibility that by understanding the biochemical processes occurring in the mosquito, scientists may be able manipulate other responses to the parasite or they may be able to interfere with other pathogens, like viruses, that mosquitoes transmit.

Luckhart developed the project at the Walter Reed Army Institute of Research during a three-year fellowship before she came to Virginia Tech in July. She will continue to collaborate with the Army, which has a variety of research programs concerning mosquitoes because of the potential for soldiers to find themselves in areas where malaria is prevalent.

Her work is also supported by grants from the National Institutesof Health and from the World Health Organization. Luckhart earned her bachelor's degree from the University of Florida, her master's from Auburn University, and her doctorate from Rutgers University.

With her program, Virginia Tech adds a new dimension to the transgenic capabilities of the university's biotechnology effort. Other Virginia Tech researchers have gained international attention for pioneering work in developing transgenic plants and animals for the production of pharmaceuticals.
Contact: Stewart MacInnis
(540) 231-5863

Shirley Luckhart
phone: +1 540-231-5729
address: Biochemistry, 124 Engel Hall, Blacksburg, VA 24061

Virginia Tech

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to