Prioritisation of Targets

The symptoms of malaria are entirely due to the proliferation of Plasmodium parasites within the erythrocytes of infected individuals. The treatment of this is currently accomplished through the use of drugs such as Chloroquine. Whilst the erythrocytic phase of the life cycle is an obvious opportunity, a 

A key step in the identification of these key kinase targets has recently been achieved through the application of functional genomics in the mouse malarial vector system, namely P. berghei. 

The non-availability of reverse genetic tools and the inability to generate sufficient materials for proteomic analysis has rather limited the progress towards the genetic and biochemical validation of these targets. More recently however it has become possible to undertake worthwhile proteomic studies on this organism,29 and to undertake quantitative proteomic approaches (SILAC),39 plus the improvement in sensitivity in mass spectrometers will have a significant impact on research capacity to undertake these studies. 

A remarkable genetic study of the function of all of the members of the Plasmodium kinome has recently been completed by Tewari, Billker and coworkers.15 Whilst such a study, if carried out in a human Plasmodium species (e.g. P. falciparum or P. vivax) would be limited by being applicable to the erythrocytic phase of the life cycle, Tewari and co-workers used the rodent species, P. berghei, which permitted an analysis of the effects of each kinase knock-out in both asexual and sexual stages of the life cycle. As noted 

There is strong evidence for the involvement of host (i.e. Human) cell kinases in the facilitation of the life cycle of the parasite. This is not surprising the parasite has evolved and adapted to its complicated life cycle and has presumably made use of the most efficient mechanism to drive its own proliferation, evade the host immune system, and preserve and protect those cells it has elected to grow within. Two recent studies have underscored this notion, and presented a number of host candidate kinases. The first study makes use of a collection of human kinome-related siRNAs to test their potential for reducing the proliferation of malaria parasites in human hepatocytes.41 Five host cell kinases were identified as being required for 

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