Decoding malaria’s ‘post code’ provides a potential target for drugs

[ The University of Melbourne Voice Vol. 3, No. 1  14 April - 12 May 2008 ]

By Nerissa Hannink

Research at the University of Melbourne has revealed the code used by the malaria parasite to move essential proteins around inside its structure.

The research could allow the design of a drug which would confuse this communication process and kill the parasite, as well as providing insight into the parasite’s evolution.

A paper on the research – co-authored by researchers in the Walter & Eliza Hall Institute and the University’s Department of Botany – has been published in Proceedings of the National Academy of Sciences.

Professor Geoff McFadden (Botany), who led the University’s research team, says that to make energy for its survival, malaria needs specific proteins delivered to certain sites inside it.

“The malaria parasite makes its energy in a cell compartment called the plastid, a structure similar to a plant chloroplast but not used in photosynthesis,” he says.

“We focused on the plastid as a parasite target because it is relatively simple and isn’t present in humans.”

He says protein delivery to sites in the plastid is achieved by the proteins having a certain ‘post code’ – a peptide known as a protein targeting sequence – which directs it to its destination.

”To decipher the code we mutated the amino acids which make up the targeting peptide to check which parts were essential for plastid transport and which were not.”

“We discovered that the malaria parasite has a developed a clever trick – to have a very general plastid targeting code, which may have enabled it to evolve faster.”

Just a positive charge in a certain place and an affinity for water is all the protein needed to find its way to its destination.

If the transit peptide had these essential characteristics – no matter what order its amino acids were in, or even which ones were included – the protein could enter the plastid.

“We now have the potential to use the relative lack of sophistication in this system as a way to confound it. If we can disable the mechanism that reads the post code, we could probably stop the entry process and kill the parasite,” he says.