Last Updated: 11/12/2025
Study on the epigenetic regulation mechanism of mutual expression of Plasmodium falciparum surface antigen var gene family
Objectives
This project aims to further explore the epigenetic mechanism in controlling mutually exclusive expression of var genes by:
- identifying transcription factors which associate with var anti-sense lncRNA in transcriptional regulation of var genes;
- characterizing novel lncRNAs and transcription regulators that control silencing of var genes in association with PfSET2vs; and
- uncovering key regulators and their functional roles in controlling mutually exclusive expression of the var gene family in a broad manner.
Plasmodium falciparum, the most deadly parasite of human malaria, has a variant surface antigen gene family consisting of multiple var genes that contribute to a major pathogenesis event in severe malaria. Through a clonal expression profile of var genes controlled by epigenetic regulations, P. falciparum could avoid the host antibody response and spleen-dependent parasite killing as an immune evasion mechanism. Recently, it was demonstrated that a histone lysine methyltransferase PfSET2vs regulates silencing of the entire var gene family. In addition, recently a previously unknown role of var-derived antisense long noncoding RNAs (lncRNAs) was discovered in transcription of var genes. However, the molecular mechanism of mutually exclusive expression of the var gene family still remains unknown nowadays. This study will shed light on understanding how P. falciparum escapes human immune system via epigenetic mechanisms regulating mutually exclusive expression of var genes, and provide new targets in the development of malaria vaccines and antimalarials.
Jan 2016 — Dec 2019
$93,613
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