Identification and characterization of insulator elements and proteins in Plasmodium falciparum

Abstract

Malaria, a life-threatening disease is becoming a major concern on a global scale due to the resistance to the available drug treatment and the lack of an effective vaccine. Plasmodium falciparum, the deadliest Plasmodium species responsible for severe malaria, exhibits antigenic variation through mutually exclusive expression and timely switching of var genes which is responsible for the enhanced pathological complexity during the infection and longevity of the infection. The exact regulatory mechanism of antigenic variation is still unclear, although research to date suggests the potential roles of characteristic positioning of var genes on chromosomes, their subnuclear organization, epigenetic modifications, and non-coding RNAs in the expression of var genes in a mutually exclusive manner. In this study, we are identifying the putative insulator-like proteins in Plasmodium falciparum and investigating the prospect of insulators serving as the possible regulators involved in the mutually exclusive expression of var genes. Through the in-silico approach and wet lab experiments, we have identified the putative insulator-like proteins and validating their role through qPCR followed by overexpression of the proteins of interest. Overall, we are also aiming to identify the putative chromatin architectural proteins in Plasmodium falciparum. Collectively, this study identifies the putative insulator-like proteins in Plasmodium falciparum and provides future directions to characterize their role in var gene expression and 3D genome organization.