The scourge of malaria is a grim threat hanging over much of the developing world. Faced with the disease's intimidating statistics, Shirley Luckhart, from the University of California, Davis, USA, and her collaborators have a goal: to produce mosquitoes that are immune to transmitting the deadly parasite. According to Luckhart, when mosquitoes dine on an infected human, in addition to filling up on malaria-spiced blood, the insect consumes a cocktail of human hormones. Having already found that a dose of human insulin reduces the insects' lifespan and having successfully designed malaria-proof mosquitoes by activating the same cellular processes that are triggered by insulin, Luckhart and student Anna Drexler decided to look at the effect that another close relative of the insulin hormone – insulin-like growth factor 1 (IGF1) – would have on the insect and its ability to transmit the lethal infection (p. 208).
First, Drexler – with colleagues Eric Hauck and Elizabeth Glennon – tested the effects of human IGF1 on mosquito cells in a test tube to find out whether the insect cells carried the essential cellular machinery that is necessary for the cells to respond to the human hormone, and she was relieved to find that the insect cells did respond. However, isolated cells are much less complex than an intact mosquito, so Drexler next had to test how the insects reacted to IGF1-spiked blood meals, and the first thing that she investigated was whether the hormone could survive intact in the insect's gut.
Adding radioactive IGF1 to a blood meal, Mark Brown and Andrew Nuss, from the University of Georgia, USA, analysed how much of the intact hormone remained undigested in the mosquito's gut and were pleased to find that it was still intact 24 h later. They then checked for radioactivity in other parts of the mosquito's body, and found that the hormone had also been transported to the thorax and head. Finally, Drexler tested to see whether the same cellular machinery that had been activated in the test tube cells was triggered in the intact mosquitoes, and sure enough, she saw similar signalling cascade proteins being activated.
Having confirmed that the mosquitoes could respond to the human hormone, Drexler moved on to test the physiological effect that IGF1 had on the insects by feeding the hormone to them in blood meals at concentrations found naturally in healthy humans. Monitoring the mosquitoes' survival rates, Drexler was amazed to see that the insects that had been fed the lowest IGF1 concentrations lived 23% longer than those that had been fed a hormone-free blood meal. So, instead of shortening the insect's life expectancy, as insulin had done, IGF1 was extending it. And when she investigated the effect that the hormone had on the number of cysts – which produce the next infectious parasite life stage 10 days after consuming an infected meal – on the insect's gut, Drexler found that the number of cysts was drastically reduced. Normal levels of human IGF1 could actually reduce the infectiousness of an insect bite.
However, Luckhart explains that human IGF1 levels drop dramatically during malaria infection, so Drexler tested the effect that these lower IGF1 levels in a blood meal from an infected human had on the number of infectious cysts, and this time the number increased. ‘This trend suggests that as the severity of a malaria infection increases, parasite transmission also increases, and this could have important epidemiological consequences in the human population’, Luckhart says, although she and Drexler are optimistic they can alter the effect that IGF1 has on parasite infectivity to produce a mosquito that is even more malaria proof.
