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Targeting epigenetic regulation of malaria blood‐stage infections
Author(s) -
Duraisingh Manoj
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.270.2
Subject(s) - epigenetics , histone , biology , plasmodium falciparum , malaria , transcriptional regulation , transcription factor , regulation of gene expression , gene , microbiology and biotechnology , immunology , genetics
Epigenetic mechanisms control a variety of critical processes through the life‐cycle of the malaria parasite P. falciparum . In the blood‐stage of infection, this includes antigenic variation of proteins on the surface of parasite‐infected red blood cells that enable sequestration within the host microvasculature and organs, as well as the expression of genes required for transition to the transmissible sexual stage of the parasite. Key histone‐modifying enzymes have been identified as regulators of distinct transcriptional programs underlying these processes. We have focused our research on the histone deacetylases (HDACs) of P. falciparum , that enzymatically remove the acetyl group from histones to regulate transcription of specific gene sets. P. falciparum expresses one class I HDAC, two class II HDACs and two class III HDACs. We have been studying the functions of these HDACs in blood‐stage infections, to establish how they regulate different transcriptional programs and cellular processes in a ‘division of labor’. We are exploring how we can chemically target the essential functions of the P. falciparum HDACs to disrupt and halt proliferation and transmission of this deadly parasite. Support or Funding Information Burroughs Wellcome Fund