Virginia Tech wins $2.7 million grant to protect people from malaria

06/27/05

Blacksburg, Va. Virginia Tech researchers in the College of Agriculture and Life Sciences and the College of Science will join researchers at the Mayo Clinic and the International Center for Insect Physiology and Ecology in Kenya, in a $2.7 million research project to help developing nations reduce the danger of malaria. The project is funded by a grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health initiative.

Jeffrey R. Bloomquist, professor of toxicology and pharmacology in the department of entomology at Virginia Tech, is principal investigator of the three-year project. Collaborating Virginia Tech researchers are Paul R. Carlier, associate professor of chemistry, Sally L. Paulson, associate professor of entomology, and Eric Wong, professor of animal and poultry sciences. Other researchers include Yuan-Ping Pang, professor of pharmacology at the Mayo Clinic, and John Githure, head of the Human Health Division of the International Center for Insect Physiology and Ecology.

The project aims to develop an insecticide to use on nets suspended over beds where people sleep. The insecticide needs to have two specific characteristics. It will be targeted specifically to the mosquito species that transmits malaria, Anopheles gambiae, and will not be toxic to humans or other animals.

"There are regions of the world where millions of people are made ill and many die, especially young children, because of malaria," Bloomquist said. "A proven way to control malaria in communities is insecticide-treated nets over the beds where people are sleeping. The problem is that the nets are effective for only a limited time and must be re-treated with the insecticide. However the insecticides used to re-treat the nets are too potent to be handled safely by untrained people."

The goal for this project, entitled "Molecular Design of Selective Anticholinesterases for Mosquito Control," is to make sure the insecticide is safe, Bloomquist said.

Virginia Tech researchers will use "in situ click chemistry," an approach to drug design that uses the biological target as a scaffold upon which to assemble its own inhibitor. Carlier, who was part of the team that established this technique, will be responsible for the design and synthesis of novel inhibitors.

"We believe that 'click chemistry' when applied to Anopheles gambiae will provide tremendous advances in potency, species selectivity, and resistance prevention," Carlier said. By using molecular information from the insect itself to prepare an effective chemical, this approach promises to bring an unprecedented level of efficacy and safety to insecticide design.

The work requires a global collaboration of experts in different fields. Paulson will be in charge of the mosquito rearing and whole insect bioassays, while Wong will be responsible for cloning the genes and expressing enzymes for bioassays. The computational determination of protein structures in Anopheles gambiae and how they interact with inhibitors at the atomic level will guide the insecticide design. This work will be conducted by Pang on dedicated terascale supercomputers at the Mayo Clinic.

The work at Virginia Tech will be connected with the ICIPE at Kenya where Githure will supervise the field trials with candidate insecticides. When the project is successful, rights to the technology will be made available to the developing world.

"Our primary issue is making sure it is safe," Bloomquist said.

Source: Eurekalert & others

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