Human malaria parasite, Plasmodium falciparum, has a complex life cycle, which involves the developemnt of various morphologically distinct stages in both mosquito vector and human host. Development and differentiation of the parasite coincides with expression of different pattern of gene expression. To understand how the parasite regulates its gene expression, we have cloned the P. falciparum gene encoding histone deacetylase (PfHDAC), a key transcription modulator involved in the modification of histone proteins and their interaction within chromatin. PfHDAC shows about 50% homology with mammalian histone deacetylases. And, like most of the mammalian enzymes, this protein is expressed mainly in the nucleus of mature parasites. Recently the drugs targeting mammalian histone deacetylases were shown to exhibit the inhibitory activity against apicomplexa protozoan including Plasmodium spp. With the widespread of drug resistance in malaria parasites, identification of this protein in P. falciparum is critical for the future development of novel therapeutics against malaria parasites. We're currently expressing this enzyme for further biochemical characterization and drug screening. Because of the specific expression of this gene during parasite life cycle, we are targeting this gene for disruption in order to make an attenauted a parasite. The gene disruption is being achieved by homologous recombination with PfHDAC gene to create a null mutant. The mutant parasites will be characterized biochemically, morphologically, and for infectivity.
