Investigating the essential function of the apical polar ring in human malaria parasites

Malaria is a life-threatening disease that claims over half a million lives worldwide annually. It primarily affects young children and pregnant women. Plasmodium falciparum causes the most severe cases of malaria, which increase cardiac risks and further amplify public health concerns. The major clinical symptoms of malaria occur due to the extensive replication of parasites within red blood cells (RBCs). The emergence of resistance to antimalarials has further escalated the urgent need to identify new therapeutic targets essential for parasite replication within RBCs. Plasmodium spp., belonging to the phylum Apicomplexa, possesses a unique structure known as the apical complex. The apical complex is critical for host cell invasion and interaction. A central feature of this complex is the enigmatic apical polar ring (APR). The APR is postulated to define the parasite’s apical polarity, maintain the cytoskeletal network, and act as a nucleation center for subpellicular microtubules, shaping the parasite. However, the components and molecular function of the APR remain poorly understood in P. falciparum. Preliminary data show that PfAPR1 is a core component of the APR, located at the apex of the inner membrane complex (IMC) and associated with subpellicular microtubules (SPMTs). Importantly, PfAPR1 is essential for the parasite’s blood stage development, particularly during the invasion of erythrocytes. To determine the precise function of PfAPR1, inducible knockout parasites and advanced imaging techniques will be used to characterize how it orchestrates the function of the APR and impacts the cytoskeletal network, ultimately driving erythrocyte invasion. Additionally, this project will determine the interactome of PfAPR1 through immunoprecipitation and proximity-labeling approaches. The discovery of novel components will lay the foundation for future studies on the mechanism of APR function. Overall, this project aims to provide a comprehensive understanding of the APR and its components, potentially leading to the development of novel therapeutic targets. These interventions could combat both malaria and its associated cardiovascular complications, significantly improving public health.

Basic Science

Jan 2025 — Dec 2026

$170,896

United States