By Phil Williams
University of
Georgia
Included in the 35 are five genes that encode insulin-like peptides that probably have pivotal roles in the life cycle of the Anopheles gambiae mosquitoes. Being able to interfere with the action of these genes on a large scale could keep the mosquitoes from passing on parasites that cause malaria.
"It's important to know as much as possible about how these insects transmit malaria," said Mark Brown, an internationally known mosquito biologist at UGA. "These genes offer new information on the regulatory processes that make the transmission of disease possible."
The research was published in the journal "Science" and was funded by the National Institutes of Health.
Research team
Other researchers involved are Joe Crim and Stephen Garczynski of the UGA department of cellular biology; Michael Riehle, an entomologist, like Brown, from the UGA College of Agricultural and Environmental Sciences; and Catherine Hill of the University of Notre Dame.Malaria is one of the planet's deadliest diseases. It is one of the leading causes of sickness and death in the developing world. According to World Health Organization statistics from the late 1990s, 300 million to 500 million clinical cases of malaria each year result in 1.5 million to 2.7 million deaths.
Children aged 1 to 4 are the most vulnerable. Malaria is responsible for as many as half of the deaths of African children under age 5. It kills more than 1 million children -- 2,800 per day -- each year in Africa alone. In regions of intense transmission, 40 percent of toddlers may die of acute malaria.
Peptides govern reproduction
Anopheles, the African malaria mosquito, develops fast in water. Its reproduction cycle begins with successive blood meals from humans. Regulatory peptides acting as neurochemicals and hormones govern these processes, so describing and understanding these peptides are crucial steps toward control."At this point the exact function of these genes is speculative," said Crim, a peptide-reception biologist. "None of these regulatory peptides was previously known for Anopheles. But their importance is clear."
The new study is part of an announcement made this week of a functional completion of the genome for Anopheles gambiae. The achievement, by a number of labs, could have an enormous impact on future control of the Plasmodium parasites with which these mosquitoes infect humans with malaria.
Bioinformatics
The UGA team used bioinformatics -- the study of gene databases on computers -- to determine peptide-encoding genes in the Anopheles genome.Of particular importance was the revealing of five insulin-like peptides. The scientists followed intriguing hints that Plasmodium appears to use insulin from either the female mosquito or the vertebrate blood meal for its own development, metabolism and reproduction.
The importance of that connection could be crucial to understanding how the parasites are passed to humans and create disease.
"Since most peptide types exist as single-copy genes, each is a target for genetic interference," Brown said, "both to unravel regulatory functions and in the long-term to engineer Anopheles where it is less hospitable for Plasmodium."
More genes?
Crim said the computer program looked for genetic sequences and found candidates for regulatory genes. There may well be more than the 35 the team found. But these are the most obvious and first targets for intervention.The completion of the A. gambiae genome is crucial to scientists. But more in-depth knowledge is needed before they can find a way to make the mosquitoes less likely to deliver the parasites that cause malaria.
To this end, the UGA scientists have begun cloning and expressing the genetic sequences. They will soon be able to determine their precise regulatory function in the mosquitoes, along with the receptors that allow the parasites to infect humans.
