Giardia is a major cause of waterborne intestinal disease and is also of basic biological interest as one of the earliest known eukaryotic organisms, with both prokaryotic and eukaryotic properties. Fran Gillin group’s orientation is unusual because they focus broadly on this organism and are not tied to specific techniques (Ann. Rev. Microbiol. 50: 679-705,1996). They ask cutting edge questions and design creative approaches to achieve incisive answers.
Fran Gillin’s lab has completed the giardial life cycle in vitro for the first time, by inducing the flagellated “trophozoite” form that colonizes the small intestine to differentiate into cysts that survive in cold water. They discovered a novel regulated secretory pathway for the transport of cyst wall proteins during encystation. Cysts infect a new host by responding to signals from the host that lead to a rapid and dramatic differentiation. Excystation entails establishing cellular polarity, cell division, attachment, increases in metabolism, and antigenic switching.
Giardia is also a valuable model for study of the prokaryotic-eukaryotic divergence and we are actively involved in biological aspects of a giardial genome project (PNAS 95:229-234, 1998; Molecular and Biochemical Parasitology, in press).
Current questions of Giardia project include:
- How are giardial genes regulated during differentiation?
- What are the cell signaling pathways in differentiation and pathogenesis?
- How are components of the cyst wall transported and how is this fibrous structure assembled?
- What are the structure and function of the unusual cysteine-rich variant surface protein of Giardia?
- What can Giardial genes and pathways tell us about the evolution of the eukaryotic cell?
- How does Giardia make people sick?