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The malaria parasite can evade our immune system by altering the way it looks during the infection. One way it does this is by frequently changing the version of a protein, PfEMP1, it leaves on the surface of red blood cells it infects. Figuring out the molecular mechanism behind this process, called antigenic variation, could offer clues on how to design effective vaccines or drugs. Sixty different members of a gene family called var each code for a different version of PfEMP1, but only one of these genes is turned on at a time. Alan Cowman of the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia, and his colleagues are investigating how the parasite manages to keep all but one gene silent. On page 1004, they report that an active ‘promoter’ — a regulatory stretch of DNA adjacent to the genes — is sufficient to inactivate all but one of the var genes. Cowman spoke to Nature about the implications of his results.

How can this finding be applied to the development of more effective malaria drugs or vaccines?

It increases our understanding of the basic biology of the parasite. Also, understanding how the parasite controls the expression of the var gene family provides the possibility of developing compounds that inhibit the process or alternatively allow the simultaneous expression of all of the PfEMP1 proteins. While these would be useful experimental tools, they would also allow us to ask the question: would these compounds be useful drugs if they do not kill the parasite but make it more open to immune attack?

How has the malaria parasite managed to get so good at evading immune responses?

There is enormous selective pressure placed on it by the host immune system. It has come up with a number of mechanisms to evade immune responses at different stages of its life cycle. It also has numbers on its side. There can be up to 1012 parasites in a single infection and this provides enormous potential for variation.

Can we develop an effective malaria vaccine?

Humans can develop good immunity to malaria, which suggests that it is possible, but it requires an understanding of the mechanisms and the parasite molecules involved. I think with a continued and increasing investment in both basic and translational research over a long period of time and with effort and perseverance, it should be possible.

What's the next step in this research?

We want to identify the proteins directly involved in silencing and activating the var gene family and therefore the molecular framework that controls antigenic variation.