Student Number : 9503239E - PhD thesis - Faculty of Science / Malaria is one of the most debilitating pathogenic infections known to man, responsible for approximately three million deaths annually, primarily children in sub-Saharan Africa. The parasite has evaded multiple attempts at eradication, predominantly through the complexity of its life cycle, the ability to elude host immune response, and gametocyte formation to ensure dissemination. The recent completion of the genome sequence has opened up a multitude of avenues for exploration and identification of novel drug and vaccine targets, as well as providing a glimpse into the complex mechanisms that have contributed to the success of this pathogen. The mechanisms of gene regulation, especially those governing gametocytogenesis, have, however, not yet been elucidated. In this research, differential display has been used to identify some of the genes that are differentially expressed between the asexual parasite and gametocyte stages of P. falciparum. Numerous genes involved in diverse aspects of metabolism, protein synthesis and immune evasion were identified. A combination of BLASTN and BLASTX similarity searches was used to categorize and increase the confidence with which a transcript could be identified. Expression data for confidently identified genes were confirmed using reverse slot blot and available microarray data. PfMyb2, a novel transcription factor which may regulate genes involved in gametocytogenesis, was characterized. The DNA binding domains of the protein were cloned and expressed as a histidine fusion protein. Mobility shift assays were used to assess the in vitro binding capability of the recombinant 6xHis-PfMyb2, which bound to oligonucleotides containing the consensus Myb regulatory element. Two of the oligonucleotides represent sequences located within promoters of P. falciparum genes (Pfcrk1 and Pfmap1) known to play a role in regulating the cell cycle, a function ascribed to many members of the vertebrate Myb family. The identification of PfMyb2 as a bona fide transcription factor is a first step into gaining some insight into the many regulatory processes that occur during the life cycle of this complex organism. A better understanding of the molecular mechanisms that govern its survival is essential for the ultimate eradication of this deadly parasite.