This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Giardia lamblia is a water-borne, intestinal pathogen that triggers a form of diarrhea called giardiasis. This early diverging eukaryote infects over 250 million people worldwide and causes a wide range of symptoms from asymptomatic to chronic infection to intestinal malabsorption and weight loss. The life cycle of Giardia switches between the cyst stage when the parasite is first ingested in its water-resistant and dormant form and the trophozoite stage when the cysts are passed to the stomach and released to the small intestine where it attaches, divides and finally completes its life cycle when it is excreted in the feces as infective cysts. After Giardia has inhabited the small intestine, it constantly has to migrate and re-attach to the intestinal epithelium so that the parasite is not swept away since cells in the intestine are continuously being produced and replaced. The flagellum helps in the movement of the parasite while the ventral disk, one of the cytoskeletal components helps the pathogen attach to the epithelium. There is a strong connection between the cytoskeleton and Giardia virulence, since it is the cytoskeleton that helps the parasite move and prevents it from being swept away. Previous research studies have identified the association of cytoskeletal proteins called alpha giardins to the Giardia cytoskeleton. The alpha giardin family consists of 21 members that may play a pivotal role in excystation where the parasite converts from the cyst to the trophozoite form. Currently, we have been able to express, purify and crystallize the first member from the alpha giardin family, alpha-11 giardin. Our structural work on alpha-11 giardin has revealed two new structures, the apo structure of alpha-11 giardin to 1.1 and the calcium-bound structure of alpha-11 giardin to 2.93 , which has revealed a new type of calcium binding site not previously reported before. We wish to continue our structural studies on the alpha giardin family of proteins, which include

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001209-28
Application #
7598248
Study Section
Special Emphasis Panel (ZRG1-BPC-E (40))
Project Start
2007-03-01
Project End
2008-02-29
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
28
Fiscal Year
2007
Total Cost
$199
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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