These studies led to the dissection of the intracellular motor components, which comprise only limited regulators of actin dynamics. Less well understood is parasite egress out of its host cell, an active, motility-dependent process that is mediated by parasite-encoded proteases. Generation of a set of loss-of-function mutants established the concept of live, genetically attenuated parasites as an experimental whole organisms vaccine. Identification of vital functions during the intra-hepatic parasite expansion phase is an important stepping stone towards the systematic identification of parasite and host factors that mediate intracellular replication, nutrient acquisition, and maturation of the malarial parasite.
In the future, we aim at translating the findings in the model rodent malaria system to the human parasite. Importantly, we wish to greatly expand our collection of liver-stage arrested parasites by deletion of additional genes and stage-specific expression of engineered inhibitors. Our long-term goal is to generate tailor-made mutants and tools to block the Plasmodium life cycle at will. We believe that these approaches will enhance our understanding of Plasmodium cell biology and contribute to the rational design of novel intervention strategies.