The mechanisms underlying the production of natural mosquito repellents by human beings

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Some human beings are bitten more than others by mosquitoes. From an evolutionary perspective this is fundamentally important since those that get bitten less often are less likely to die from lethal mosquito-borne diseases like malaria. Thus there is likely to be a selective advantage for being less attractive to malaria mosquitoes. Whether or not this is due to natural selection in humans, or because mosquitoes are simply avoiding unsuitable hosts is unknown, but our previous studies show that human differential attractiveness to mosquitoes is due to the natural production of key repellent chemicals given off by individuals who rarely get bitten. Essentially this could be thought of as the first line of defence related to the immune system. In a recent pilot study we showed that for Europeans how attractive you are to mosquitoes is controlled by your genes. We intend to extend this line of research and carry out a similar study amongst an indigenous African population that has traditionally been under intense selective pressure from malaria. Here we would anticipate finding genes for new repellent molecules that are under selection. The natural repellent chemicals that we have identified from our study of Europeans are effective repellents when applied to the skin, but what remains unknown is how the body produces these chemicals and which genes control this process. Preliminary studies show that some of the repellents can be produced by skin cells and there are likely candidate genes as potential targets. In this study we aim to compare identical and non-identical twins using chemical ecology and molecular genetic techniques to identify how the chemicals are produced and which genes are involved in production and regulation. This will give an understanding of how the body provides an important component of natural resistance to mosquitoes and provide a new potential treatment which stimulates production of these repellent chemicals in susceptible human beings. This could allow us to develop a more persistent application and eventually an oral treatment in the form of a pill which enhances the production of natural repellents to protect against mosquito bites, minimising the need for repeated skin-applied volatile repellents. This research has the potential to find new mosquito repellents that could be produced systemically, and elucidate one of the least understood innate immunity mechanisms: how we use chemical warfare to hide from vectors.