The mechanism for Plasmodium falciparum to grow and sequester in the mature human erythrocyte, a quiescent cell lacking all organelles and machinery to synthesize proteins, has remained largely unknown. We have observed the differential expression of two small GTP-binding protein, Arf1 and Rab1, in P. falciparum. PfArf1 transcript was detected predominantly in the asexual erythrocytic stage of merozoites, while the transcript of a P. falciparum Rab1 gene was detected mainly in the sexual stages. The differential expression of PfArf and PfRab1 suggests that specific protein transport machinery may be evolved to accommodate the stage-specific expression of various proteins essential to the parasite development, and the transcription control of these genes may be tightly linked to differentiation. To understand how the parasite regulates its gene expression, we went ahead and cloned the P. falciparum gene encoding histone deacetylase (PfHD), a transcription modulator involved in the modification of histone proteins and their interaction within chromatin. PfHD 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. Both PfArf1 and PfHD expressed in similar stages of parasites as suggested by the EM studies further implicates the closely association of transcriptional control and protein trafficking machinery. 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.
