Identified: DNA that controls the malaria parasite’s disguise mechanism

Professor Alan Cowman, Dr Brendan Crabb and their research teams at WEHI have identified how the most lethal malaria parasite, Plasmodium falciparum, is able to disguise itself from the human immune system.

This discovery builds on the work published in the 9 April 2005 issue of the journal Cell, in which Professor Cowman and Dr Crabb reported that to avoid detection and destruction, the parasite controls expression of 60 key virulence genes, effectively disguising itself from the human host’s immune system. The new discovery identifies the DNA sequence that is needed to switch these genes on and off.

With this greater understanding of the parasite’s disguise-switching mechanism, scientists will now attempt to identify the activating proteins that enable the parasite’s 60 disguises to be switched.

Further along the way, research will concentrate on the design of a drug candidate molecule that will, in effect, freeze the parasite’s capability to change its disguise.

With the parasite thereby converted into a stable and unchanging target, the immune system of the human host should be able to raise an effective immune response against the recognised invader. This should lead to a steep reduction in the severity of the debilitating symptoms that usually accompany malarial infection.

Other members of the discovery team are Till Voss, Julie Healer, Allison Marty, Jennifer Thompson and Michael Duffy.