Thursday, November 21, 2024
11/21/2024
PROJECT SUMMARY The complex life cycle processes of encystation and excystation in Entamoeba represent potential targets for therapeutic intervention but have not been studied directly in the human pathogen Entamoeba histolytica because of an inability to produce cysts in a laboratory setting. Instead, scientists have been forced to rely on studies with the distantly related reptile pathogen Entamoeba invadens. Our lab has established a method for reproducible encystation of E. histolytica in laboratory culture and in this project we propose to develop reproducible, high efficiency excystation as well. E. histolytica causes amoebic dysentery in ~100 million people each year worldwide, although as many as 1 billion people may be infected each year as only ~10% of infections result in symptomatic disease. The inability to study encystation and excystation in the laboratory has greatly hindered investigation of the life cycle and infection process. The long-term goal of our research program is to determine how E. histolytica senses and adapts to different environments it encounters during infection. Encystation and excystation are the two key adaptations, allowing Entamoeba to continue the disease process through dissemination of infectious cysts. Having established a reproducible system for encystation of E. histolytica in culture, we are now able to do the same for excystation, thus allowing us to study these critical processes in the lab to pursue an understanding of how E. histolytica senses and responds to environmental cues that signal conversion from motile trophozoite to infectious cyst and back. As part of our long-term goal, the overall objective of this proposal is to develop a reproducible method for high efficiency excystation of E. histolytica in vitro cysts. To this end, we will use two approaches: (1) increase excystation efficiency with standard in vitro cysts; and (2) produce in vitro cysts that exhibit high efficiency excystation. We will apply these two approaches iteratively, such that we will identify the optimal combination of conditions for both encystation and excystation that leads to reproducible, high efficiency excystation. This research will have a significant impact by laying an important foundation for future studies on excystation of the human pathogen such that we can identify and characterize the roles of key genes required for this essential disease process.
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