| Malaria is an ancient disease that remains a major public health problem, killing an estimated 1-2 million people annually (Murrary et al., 2012). The disease is caused by the cyclic asexual replication of the Plasmodium parasite within the erythrocytes of an infected host. Transmission, however, is solely dependent on the commitment of a small subset of the asexual parasites to undergo terminal sexual differentiation and form gametocytes instead. Despite the essentiality of gametocytes to disease transmission, relatively little is known about the mechanisms that lead to P. falciparum gametocyte formation. To gain insight into these mechanisms, we conducted a piggyBac transposon-mediated insertional mutagenesis and screened for parasites that no longer form mature gametocytes. We were able to identify 16 genes that are putatively essential for gametocytogenesis, none of which had previously been implicated. We were able to hierarchically order these genes and found that a subset act during commitment and the initial differentiation into a gametocyte from an asexual parasite and another subset acts during the early stages of maturation. For my dissertation, I focused on two genes which did not have a previously assigned function. One of these genes appears to be a marker for sexually committed cells. The other appears to be essential for maintenance of the erythrocyte membrane rigidity and stability during gametocyte maturation. |
