Malaria HATs in Transcription Regulation

  • Cui, Liwang (PI)
  • CUI, LIWANG (PI)

Project: Research project

Project Details

Description

The increasing burden of malaria, in part, due to drug resistance in the parasite Plasmodium falciparum,
demands new therapies. Recent research in the field of transcription has demonstrated the functional
importance of chromatin in regulating gene expression in eukaryotes. Enzymes that modulate chromatin
structures have a profound effect on controlling gene expression. Among these enzymes, histone
acetyltransferases (HATs), which transfer the acetyl group from acetyl-CoA to the lysine residues in the N-
terminal tails of histones, are the best studied. The antiparasitic effects of drugs that disturb histone
acetylation and recent studies from our group on the chromatin remodeling factors in P.falciparum
demonstrated that dynamic histone acetylation is an important epigenetic mechanism of transcription
regulation and plays a prominent role in development of the malaria parasite. Thus, we propose to 1)
characterize two families of transcription-related HAT proteins, 2) determine their functional roles in global
transcription regulation, and 3) identify the subunits of multiprotein HAT complexes in P. falciparum. HAT
proteins will be characterized using molecular and biochemical approaches, and their functions in parasite
development and transcription regulation will be determined by targeted gene disruption and genome-wide
expression analysis. This proposed research aims to reveal the epigenetic mechanisms in transcription
regulation that controls the parasite development and virulence. The fundamental importance of histone
acetylation in gene regulation and the great potential of HAT and histone deacetylase as drug targets
underline the significance of research in this area, which may lead to novel antimalarial drugs.
Malaria is still a major public health problem in many countries. Its recent resurgence in prevalence is
partially due to drug resistance. This study aims to characterize the functions of a group of enzymes that
regulate parasite gene expression, which may lead to the design of novel antimalarial drugs.
StatusFinished
Effective start/end date1/1/0712/31/12

Funding

  • National Institute of Allergy and Infectious Diseases: $398,077.00
  • National Institute of Allergy and Infectious Diseases: $408,129.00
  • National Institute of Allergy and Infectious Diseases: $143,075.00

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