Giardia lamblia is the most common disease-causing parasite in the United States responsible for an estimated 3 million cases a year. Besides causing problems in day-care centers, travelers, backpackers, and homosexuals it not uncommonly contaminates water supplies and has been responsible for massive epidemics. The organism lives in the small intestines and causes diarrhea, abdominal pain, nausea and vomiting. Symptoms are commonly intermittent and long lasting. An environmentally resistant cyst form is passed in the feces and because large numbers of cysts are excreted and only a few can initiate infection, infections are common. During the past year a system for stably placing DNA into Giardia was developed. This allows the expression of any protein in the organism. For instance, a foreign protein, or more of a protein normally present, or a protein defective in some way that would interfere with normal function could be made. We are presently using this system to study 3 major questions. One question is how Giardia control antigenic variation. We have been able to express a particular surface antigen in Giardia and see if this effects infectivity. We are currently using this system to understand how certain protein antigens are made and others not made. In other studies, a foreign model protein with known and characterized secretion and processing in more developed cells was introduced into Giardia. We are comparing how Giardia handles this protein compared to mammalian cells. In order to survive and infect others, Giardia forms a cyst wall. Two constituents of the cyst wall were previously defined in this laboratory. Both proteins are not normally made or found in the growing form of the parasite but are induced or made when the growing form of the parasite (trophozoite) is cultured under the right conditions. We are presently studying how Giardia controls the production of cyst wall proteins and found that the controlling elements lie immediately upstream to the cyst wall protein gene. Exactly which small DNA pieces are important is currently being studied.
