Applying chemical genetic tools to the study of phospho-signalling pathways in malaria parasites

• Malaria protein kinases are a promising drug target.
• Challenges lie in defining the nature of key phospho-signalling in malaria.
• Phosphoproteomics now revealing phospho-signalling networks
• Chemical genetics can be employed to further understand malaria phospho-signalling.

Until very recently there has been very little information about the phospho-signalling pathways in apicomplexan parasites including the most virulent species of human malaria parasite, Plasmodium falciparum. With the advancement of mass spectrometry-based phosphoproteomics and the development of chemical genetic approaches to target specific parasite protein kinases, the complexity of the essential role played by phosphorylation in maintaining the viability of apicomplexan parasites is now being revealed. This review will describe these recent advances and will discuss how these approaches can be used to validate parasite protein kinases as drug targets and to determine the on- and off-target action of protein kinase inhibitors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.