Virginia Tech has been selected for a grant offer from the Foundation for the National Institutes of Health (FNIH) of $2.7 million to support work to reduce the danger of malaria.
The project is among 43 groundbreaking research projects to improve health in developing countries, supported by $436 million from the Grand Challenges in Global Health initiative.
The Grand Challenges initiative was launched by the Bill & Melinda Gates Foundation in 2003, in partnership with the National Institutes of Health, with a $200 million grant to the FNIH and is a major international effort to achieve scientific breakthroughs against diseases that kill millions of people each year in the world’s poorest countries. It is funded with a $450 million commitment from the Gates Foundation, $27.1 from the Wellcome Trust, and $4.5 million from the Canadian Institutes of Health Research (CIHR). The initiative is managed by global health experts at the Foundation for NIH, the Gates Foundation, the Wellcome Trust, and CIHR.
Jeffrey R. Bloomquist, professor of toxicology and pharmacology, in the department of entomology in Virginia Tech’s College of Agriculture and Life Sciences, is principal investigator of the three-year project. Collaborating researchers are Paul R. Carlier, associate professor of chemistry in the College of Science, Sally L. Paulson, associate professor of entomology in the College of Agriculture and Life Sciences, and Eric Wong, professor of animal and poultry sciences in the College of Agriculture and Life Sciences, at Virginia Tech, and 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. A proven way to control malaria in communities is insecticide-treated nets over the beds where people are sleeping,” Bloomquist said. “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.
The Virginia Tech researchers will use an approach called “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.
The Foundation for the National Institutes of Health was established by the United States Congress to support the mission of the National Institutes of Health – improving health through scientific discovery. The Foundation identifies and develops opportunities for innovative public-private partnerships involving industry, academia, and the philanthropic community. A non-profit, 501(c)(3) corporation, the Foundation raises private-sector funds for a broad portfolio of unique programs that complement and enhance NIH priorities and activities.