Philanthropy For Basic Science: Malaria & Other Parasitic Diseases

DNA Replication and Var Gene Expression in Plasmodium falciparum

DR. DEITSCH is looking at the process of antigenic variation, which allows P. falciparum to escape the immune response of the host. Key to this process is a large family of var genes, which encode erythrocyte membrane proteins (PfEMP1). During infection, small sub-populations of parasites arise that express different var genes and thus different versions of PfEMP1. When a strong immune response is generated against the dominant variant antigen in the population, parasites expressing an altered version can survive and re-ignite the infection. Previous research showed that S-phase of the cell cycle is important in regulating var gene expression. To allow study of this, Dr. Felomona Li, a member of Dr. Deitsch's lab, developed a technique to halt parasite replication at the start of S-phase. She also perfected a version of the recently developed technique of DNA-FISH (DNA fluorescent in situ hybridization), which can localize individual genes within the nucleus of single parasites. Dr. Deitsch's team used a variant of this technique to visualize non-coding or "sterile" RNAs associated with var genes. They found that in late stage parasites undergoing DNA replication, the "sterile" transcripts cluster in structures in the nucleus, which they called "varR bodies." They hypothesize that these may be important for programming the gene expression profile of the cell.