Giardia lamblia is the most common disease-causing parasite in the United States responsible for an estimated 3 million cases a year. Previously a system for placing DNA into Giardia was improved (stable transfection) so that enough any protein could be expressed to make it easily detectable in the parasite. This allows the expression of any protein in the organism and experiments to understand how proteins are made, transported and secreted in this very unique organism. Giardia has the ability to change its surface relatively frequently, a process called antigenic variation. To understand how the surface antigens or VSPs are made and transported to the surface is important because inability of the parasite to have VSPs or ways to block its biological activity are ways to prevent infection or disease. To determine the outer most portion of the VSP small molecular markers that could be detected by antibodies in live organisms were added to various sites in the molecule. Using the transfection system mentioned above, we showed that the outside of the molecule is made up of at least 2 regions, both in the first portion of the protein about 90 amino acids apart. This marks the region of the molecule that varies the most and is recognized by the host. The same transfection system was used to explore the molecular mechanisms involved in antigenic variation. Understanding how antigenic occurs can lead to ways to prevent the process and control infections. Earlier studies from this and other laboratories showed that the control of the production of proteins that are made by the parasite most of the time( transcription of house keeping genes), resides in the sequence of DNA just upstream of the gene. Similar types of studies involving VSPs showed that the control of production of these proteins differs from that of other proteins in Giardia. The upstream region of these proteins were unable to support production of these proteins in a manner that mimicked antigenic variation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000350-19
Application #
6508495
Study Section
(LPD)
Project Start
Project End
Budget Start
Budget End
Support Year
19
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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