October 2, 2002. Copyright 2002. Graphic News. All rights reserved.
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Picture captions:
GN14325 -- Picture shows the Anopheles gambiae mosquito, the primary malaria-causing vector in humans. A. gambiae transmits the malaria-causing parasite Plasmodium falciparum to humans, where the parasite completes several stages of its life cycle. MUST CREDIT: Jim Gathany, U.S. Centers for Disease Control 
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GN14326 -- Picture shows children at risk in sub-Saharan Africa. More than 90% of the worldÕs annual cases of malaria illnesses (500 million) and deaths (2.7 million) occur in sub-Saharan Africa. MUST CREDIT: M. Coluzzi, Universitˆ la Sapienza, Roma, Italy
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Genome discoveries could lead to new anti-malarial treatments

LONDON, October 2, Graphic News: New ÒdeodorantÓ mosquito repellants, insecticides, and mosquito vaccines are some of the malaria-fighting tools that it may be possible to develop using information from the newly-sequenced mosquito genome. 

Scientists hope the genetic blueprints of the Anopheles gambiae mosquito and of Plasmodia -- the parasite the causes malaria -- will lead to breakthroughs to treat the disease that afflicts over 500 million people and cause nearly three million deaths each year. The gene sequence of A. gambiae, the primary mosquito species that transmits the malaria parasite to humans, appears in the October 4 edition of the journal Science.

ÒMalaria in Africa is on the rise, as malaria parasites have developed resistance to anti-malarial drugs, and mosquitoes have developed resistance to insecticides. Knowing the mosquito genome may help researchers identify genes involved in the insectÕs ability to host the parasite, or to locate a human to infect,Ó said Don Kennedy, Editor-in-Chief of Science.

ÒNew malaria control techniques are desperately needed in Africa, and the Anopheles genome has an important part to play in fighting this disease,Ó said lead author Robert A. Holt of Celera Genomics, Inc. 

To sequence the A. gambiae genome Holt and colleagues used the ÒshotgunÓ method, which involves randomly sequencing segments of DNA from all over the genome and then connecting the segments by matching their overlaps. The assembled gene map contains 278 million nucleotides, the basic units of DNA. Using software programs to identify likely genes in the sequence, HoltÕs team made a Òfirst approximationÓ of the genesÕ general functions.

After the female mosquito feeds on blood, certain proteins and lipids from her meal travel to her ovaries, helping the eggs to develop in two to three days. After she has laid the eggs, the cycle of host-finding, blood feeding, digestion, and egg development begins once again. 

Holt and his colleagues did a special study of the genes that were activated or deactivated when the female mosquito feeds on blood. They compared bits of gene-coding DNA (called expressed sequence tags, or ESTs) from blood-fed and non-blood-fed mosquitoes, and found that blood feeding activated a number of genes involved in cellular and nuclear signalling, digestive processes, lipid synthesis and transport, and egg production. Blood feeding also deactivated a variety of genes, including some involved in certain aspects of muscle contraction, vision, and metabolism.

ÒThose are the pathways that are likely to be useful in finding points of intervention for developing new insecticides or transmission-blocking vaccines,Ó Holt said.

ÒI think the most important thing the genome will facilitate in the immediate future is understanding the molecular basis of resistance to insecticides, and finding new insecticide targets,Ó he said. 

Possible Òtransmission-blocking vaccinesÓ might target specific interactions between the malaria parasite -- Plasmodium falciparum -- and the mosquito, as the parasite progresses through its complex life cycle inside the insect. Holt speculated that one way this might work is by giving a vaccine to humans that results in the production and circulation in the blood of antibodies to specific mosquito proteins. The antibodies would then be transmitted to the mosquito when the insect feeds on human blood.

Some researchers have suggested that genetically modified mosquitoes might be an effective way to combat malaria. Under this scenario, GM mosquitoes, resistant to the malaria parasite, would be released into natural populations to slow or eliminate malariaÕs transmission to humans. Such genetic modification has already been accomplished in Anopheles. But more information is needed about mosquito population ecology before scientists can evaluate how well a GM mosquito strategy might work.

Another intriguing possiblity involves the production of a Ògenetic deodorant.Ó which might subvert the mosquitoesÕ ability to find human blood, which they need to produce viable eggs. Scientists generally agree that mosquitoes must be able to recognize human-specific odours. HoltÕs team described possible A. gambiae odorant receptors. A mosquito repellant that worked by blocking such receptors may prevent the spread of malaria, simply by making it harder for mosquitoes to Òsniff outÓ their prey.
/ENDS

Source: Science