Role of chromatin modifiers in the transcription dynamics of virulence factors of the human malaria parasite Plasmodium falciparum

Malaria parasites strictly control gene expression in each phase of their complex life cycle, depending on the host environment. The control of expression is mostly at the transcriptional level, although post-translational mechanisms are also encountered (e.g. P-bodies). Transcriptional control is exerted by dynamic chromatin modification and the deliberate inhibition of chromatin modifiers may seriously interfere with or kill parasites. In this project, the researchers will focus on the role and importance of chromatin modifiers on variant gene transcription in blood stage Plasmodium falciparum parasites, which cause the most dangerous form of human malaria. These parasites are also still endemic in the Brazilian Amazon. In a previous study, the researchers have created transgenic parasite lines which permit functional characterization (via ribozymes) of chromatin modifiers. Introducing also a hemagglutinine tag, they have generated mutants in chromatin modifier genes of histone deactylases (SIR2A), histone demthylases (Jumonji-like demethylase 1, 2 and lysine histone demethylase 1, LSD-1). The researchers have also modified a DNA Cytosine methyltransferase, a acetyl histone transferase (SET2) and an AcetylCoA synthetase, which probably delivers acetyl rests for Acetyl histone transferases. They also modified three putative transcription factors of the ApiAP2 family which may be involved in variant gene transcription. Variant (var) genes encode adhesins which then may lead to severe malaria outcomes. The expected results will contribute to the understanding of the coordinating network that underlies gene transcription in blood stage malaria parasites, possibly revealing novel attack points for drugs.

Project details

Basic Science
Enabling Technologies & Assays
Genetics and Genomics

May 2018 — Mar 2021

Brazil