Last Updated: 09/12/2024
Mechanism of DNA helicase regulating the expression of pathogenic factors in Plasmodium falciparum
Objectives
The overall goal of this study is to reveal the mechanism of DNA helicases in transcriptional regulation of var genes, shed light on understanding how P. falciparum escapes human immune system, and then provide new targets for the development of malaria vaccines and antimalarials.
Plasmodium falciparum is the most deadly parasite of human malaria. P. falciparum var gene family encodes ~60 surface antigens that contribute to the major pathogenesis in severe malaria. Through a mutually exclusive expression of var genes, P. falciparum could escape the host antibody response and parasite killing as an immune evasion mechanism. The latest study revealed that var genes expression was significantly decreased upon knock-out of DNA helicases (PfWRN or PfRecQ1). Additionally, researchers have established parasites where DNA helicase was knocked out or tagged in. In order to explore the mechanism of WRN and RecQ1 in regulation of var genes expression, researcher plan to : 1) identify the binding sites of two DNA helicases on chromatin ; 2) reveal the role of DNA helicase in the regulation of the var genes’ spatial location in nucleus; 3) analyze how active transcription marker or silencing marker plays together with DNA helicases to regulate var gene expression 4) identify proteins which associate with DNA helicases in transcriptional regulation of var genes; 5) characterize functional roles of key partner proteins in controlling var genes expression.
Jan 2018 — Dec 2021
$78,932
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