AN essential switch in the life cycle of the malaria parasite has been uncovered by Imperial researchers.

The biological sciences team behind the Cell paper. L to R, Oliver Billker, Rita Tewari, Sandrine Deschamps and Gerald Wenig

To infect mosquitoes that transmit maleria, parasites depend on a type of molecule found in plants, named calcium-dependent protein kinase 4 (CDPK4).

Based on studies of the malaria parasite of rodents, Plasmodium Berghei, the finding, described as basic science, may give drug researchers a specific and safe target against which to screen potential anti-malarial drug compounds.

"This work identifies the first signalling molecule that we know is essential for the transmission of the parasite," said Dr Oliver Billker, Imperial research fellow and lead author.

"It is an essential molecule. If the malaria parasite doesn't have this gene function, transmission of the parasite to mosquitoes is completely disrupted. It is also only specific to development of the male gametes."

The human malaria parasite has two hosts, humans and mosquitoes. Just after the mosquito has taken a blood meal from a human, malaria parasites in the mosquito bloodstream differentiate into male and female sexual forms, named micro- and macro-gametes respectively.

In 1997, Imperial researchers discovered that the mosquito molecule xanthurenic acid is responsible for inducing development of the malaria parasite at this stage. Since then, further work has shown that xanthurenic acid specifically causes a rise in calcium levels within the parasite.

"This is an example of how we exploit genome data now," says Dr Billker. "We combine them with new methods of functional analysis which tell us what genes are active at specific stages of the parasite's life cycle - they provide great insights into the molecular components involved in signalling and regulation of the parasite.

"CDPK4 is unusual because apart from the malaria parasite and some other single-celled organisms, it is only seen in plants. This makes it appealing as a target for drug developers, who would not run such a big risk of developing a drug with strong side effects, because CDPK4-like molecules do not exist in humans."

The findings have been reported in Cell by Imperial researchers, Leiden University Medical Center, Netherlands, and the Max-Planck Institute of Infection Biology, Germany.

• Dr Oliver Billker was recently awarded a Lister Institute Research Prize for 2004, worth £150,000 over three years.