Setting boundaries: Cohesin and mutually exclusive expression of virulence genes in the human malaria parasite – PlasmoVarOrg

Mutually exclusive expression of the var gene family is critical for infection and immune evasion by the deadliest human malaria parasite, Plasmodium falciparum. All but one var gene are silenced in heterochromatic clusters at the nuclear periphery, and activation is associated with spatial separation from this repressive cluster. Until now, the factors facilitating genome organization in P. falciparum were unknown; however, we recently found cohesin complex components enriched in var gene chromatin by mass spectrometry. Genome-wide analysis of a cohesin subunit revealed two peaks flanking a single var gene locus, suggesting a role in DNA looping or chromatin domain formation at the active var gene. The proposed project will use fluorescence microscopy, genome-wide approaches, and proteomics to provide an in-depth functional characterization of cohesin and explore how it functions in the organization and transcription of the var gene family, which impacts the virulence of the parasite.