Discovering the functions of essential exported malaria proteins

The functions of at least half of the proteins encoded in the genome of Plasmodium falciparum malaria parasites remain unknown. Understanding protein function is important because many are critical for pathogenesis and/ or could become future drug targets. Proteins exported by the malaria parasite into its host red blood cell are particularly intriguing as they aid parasite survival and immune avoidance. Disrupting expression of a protein in malaria parasites and then studying the resultant phenotypic changes have traditionally been used to understand function. However, about 25% of genes for exported proteins cannot be disrupted and are considered to be essential. This makes the study of these proteins and their functions difficult and so to overcome this we have been developing genetic knockdown systems where a switch is inserted into the gene of interest so it can be rapidly be turned down at will and the resultant phenotypes examined. The aim of this project is to genetically knockdown essential genes for novel exported proteins in malaria parasites and determine their function using a suite of molecular and cellular biological assays.