Serine palmitoyltransferase and Giardial encystation
Giardia lamblia is a flagellated protozoan parasite responsible for chronic diarrheal disease in humans and animals. Giardia has minimal lipid synthesis machinery and the majority of its lipids are obtained from the small intestine of humans where the trophozoites colonize. Recent results from our laboratory indicate that sphingolipids (SLs) are also important for Giardia and they regulate encystation and cyst production. Only five SL genes are present in this parasite and they are differentially regulated during encystation. In my studies, I found that giardial serine palmitoyltransferase (gSPT) activity is upregulated in encysting cells, suggesting it might play an important role during encystation. Giardial SPT is encoded by two copies of genes (gspt-1 and gspt-2-) and both are transcribed and expressed differentially during encystation. While the transcripts of both genes are high in trophozoites, their levels are reduced in early encystation and increases again in late encystating stages of Giardia, suggesting the importance of these genes in regulating. The focus of the current research is to determine the mechanism by which gSPT regulates encystation by Giardia. My hypothesis is that gSPT activity is upregulated in Giardia cyst and knocking down of its gene expression will affect the formation of cyst. To accomplish my goal, I proposed two Specific Aims: Specific Aim-1 will include measuring the SPT activity throughout the life cycle of this parasite, while Specific Aim-2 will determine whether the knocking down of this enzyme interferes with encystation and cyst production. The results that had been generated from the current study should shed some light on the possible role of SPT in regulating the growth and differentiation of Giardia. I propose that gSPT should be considered as novel target for developing anti-giardia therapies in the future.
Delgado, Monica, "Serine palmitoyltransferase and Giardial encystation" (2015). ETD Collection for University of Texas, El Paso. AAI10000780.