Neal Yuan, 2010, Molecular Biology

Despite its widespread impact, Plasmodium falciparum, the causative agent of the most virulent form of malaria, is a parasite whose biology is one of the least understood among infectious agents. The parasite exhibits a highly adapted lifestyle that involves a 48-hour intraerythrocytic development cycle in humans during which the parasite undergoes significant morphological transformations. Such a complex developmental process necessitates a sophisticated network of genetic regulation that has yet to be fully understood.  Even so, the promoters and transcription factors necessary for transcriptional regulation have for the most part remained elusive.

Previous research has identified for the first time a putative family of P. falciparum transcription factors, the Apicomplexan AP2s (ApiAP2s). My project has employed a multifaceted approach to help further elucidate their role in gene regulation. In order to clarify the in vivo activity of ApiAP2s, I am studying the stage specific importance of ApiAP2 proteins by gene knockdown as well as a suspected ApiAP2 DNA-binding motif using luciferase expression assays.  These experiments will build on in vitro and computational work with the goal of elucidating in vivo some of the first minimal transcriptional networks in P. falciparum.  As an additional project, I have used protein binding microarrays to characterize the in vitro DNA-binding preferences of a previously uncharacterized ApiAP2, uniquely found in the malaria parasite Plasmodium vivax.  Studying the regulatory targets of this ApiAP2 may help reveal genes that are specific to this parasites pathogenicity.  Together, these experiments will help further articulate the importance of ApiAP2 transcription factors, while also opening many new avenues for further inquiry.