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UC IRVINE RESEARCHERS ALTER CHROMOSOMES OF DISEASE-CARRYING MOSQUITOES
Discovery Opens Doors to Controlling Malaria and Other Diseases by Changing Insectsà Genes
Irvine, Calif. ó UC Irvine researchers have found a way to introduce foreign DNA into mosquito chromosomes, a technique with the potential to transform future generations of the insects so they can no longer carry deadly diseases such as malaria.
A unique, mobile chunk of genetic material called a "transposon" can be used as a vehicle to plug new fragments of genes into a mosquitoÃs DNA, so they become part of an insectÃs genetic blueprint, UCI transformation biologist Anthony A. James, postgraduate researchers Craig Coates and Nijole Jasinskiene and colleagues report in the March 31, 1998 issue of Proceedings of the National Academy of Sciences.
This is the first time anyone has found a way to routinely introduce stable, inheritable foreign DNA into mosquitoes, James said. He and his colleagues hope the method will lead to the introduction of an altered genetic code into certain mosquito populationsócombating diseases such as malaria and dengue fever.
"It would be a sort of gene therapy for mosquitoes," James said.
Each year, 300 million to 500 million people worldwide become ill with malaria and several million die. Between 200 and 300 children are estimated to die from malaria each hour.
Malaria is caused by a parasite that is carried by mosquitoes and introduced into human beings when the mosquito feeds on the blood of a human host. Public health officials say the disease is now resurging worldwide because mosquitoes are growing resistant to insecticides and the malaria parasite is gaining resistance to many drugs used to prevent the disease. This resurgence is prevalent in nations where many people are too poor to afford the more effective drugs.
James began working on this area of research in 1986, focusing on genes from mosquitoesà salivary glands, where specific interactions occur between a parasite and the mosquito. By the early 1990s, he had identified areas of genes that, if altered, might be used to help block transmission of disease. But how to get a synthetic, parasite-resistance gene fragment into a mosquito so it could be passed on to further generations?
James and colleagues fruitlessly worked on ideas. For seven years, promising leads turned into dead-ends. Then James came up with the idea of using a transposon as a vehicle to introduce gene fragments into a mosquitoÃs DNA.
A transposon is a genetic taxi cab: a short chunk of DNA that has the ability to jump out of a DNA chain and move itselfóand any other genetic material it happens to be carryingóinto another part of a DNA chain.
Still, it took a fortuitous discovery for James to prove he could use transposons to introduce new DNA into a mosquito.
On a break during an entomology conference in Italy, James asked colleague Frank H. Collins of the University of Notre Dame about his latest research projects. Collins told him about a strain of mosquitoes that passed along a trait to offspring that turned their eyes white, instead of the normal dark reddish-brown. Immediately, James got an idea: Why not use the eye color trait as a marker in his research?
A team of scientists including James, Jasinskiene and Coates, as well as representatives of Notre Dame and the Centers for Disease Control and Prevention, set to work with dozens of tiny embryos of white-eyed mosquitoes. They injected them with a transposon called "Hermes," which carried a new bit of DNA that controlled eye color. Hermes originally came out of the genetic code of a housefly.
A second team of UCI researchers injected another group of white-eyed mosquito embryos with a different transposon called "mariner," which also had the eye color gene fragment plugged into it. Mariner originally came out of the genetic code of a fruit fly.
Both teams saw that offspring of the white-eyed mutant mosquitoes ended up with reddish-brown eyes, indicating the new eye color genetic fragment was successfully passed along to offspring. The bit of DNA was passed along for at least 10 generations, proving that both Hermes and mariner acted as effective DNA delivery systems.
This technology takes a first step toward generating strains of mosquitoes that cannot transmit various diseases. Scientists must next develop synthetic, disease-resistance genetic bits they can plug into transposons and then introduce into mosquitoes. They also will study how the altered genome would behave in mosquito populations.
"Much work still has to be done, especially in evaluating the effects of releasing genetically altered mosquitoes," James said.
For James, the findings validate many years of research when the answers he sought were frustratingly elusive.
"We just found some way to keep working," he said. "Year in, year out, we werenÃt seeing things. But we just continued to design experiments based on the best science."
The studies were funded by the National Institutes of Health, the John D. and Catherine T. MacArthur Foundation and the United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases.
James started his career as a student at UCI in 1969, and went on to get his doctorate in developmental and cell biology from UCI in 1979. He was on the faculty at Harvard University until 1989, when he returned to UCI to teach and perform research in the molecular biology and biochemistry department.
For more information about Anthony Jamesà research, go to his faculty home page. Images of mosquitoesmay also be downloaded. Slides are available upon request.
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