Characterizing Plasmodium proteins at the host-pathogen vacuolar interface during parasite development in the liver

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For membrane-bound intracellular parasites, the vacuole enclosing the pathogen is the portal of communication with the host cell. This membrane, therefore, functions in nutrient acquisition, protection against host defenses and in many cases must expand during infection to accommodate the developing parasite. We believe through the study of two Plasmodium proteins, UIS4 and the previously undescribed Lex3, which are present on the Plasmodium parasitophorous vacuole (PV) and its extended membrane network (TVN) in liver stage infections, we can better understand how this compartment carries out these functions. We choose these proteins because of their differential expression patterns: UIS4 is expressed early after infection and exclusively in liver cell infection, whereas Lex3 is expressed later in liver cell infection and also during blood infection. Therefore with these proteins we can compare membrane dynamics and the host cell influences of these dynamics at all mammalian infection stages. Intially we will precisely visualize and characterize the Lex3- and UIS4-positive structures in infected cells. Then, we will assess the contribution of host cytoskeletal elements and membrane transport pathways to the dynamics of the PV and TVN. Finally, we will search for host factors important for Plasmodium intracellular growth in part through identifying host protein interaction partners of UIS4 and Lex3. With these studies we will better characterize the Plasmodium-containing vacuole and improve our understanding of the factors necessary for Plasmodium intracellular development.