Diarrheal diseases kill one of every ten children by his or her fifth birthday in poor countries such as Bangladesh. Entamoeba histolytica is one of the etiologic agents. It is a human parasite that has a remarkable ability to invade and lyse host tissues. Invasive infection with E. histolytica leads to dysentery, amebic colitis, and amebic liver abscess. The imminent completion of the Entamoeba genome project provides an unprecendented opportunity to apply the approaches of genetics to the problem of amebiasis.
Three specific aims are proposed: (1) Characterize the host:parasite interface by identifying molecules recruited to this site by the E. histolytica GalNAc lectin using a yeast two-hybrid system, (2) Use a proteomics approach in conjunction with the E. histolytica genome sequencing database to further characterize novel proteins that interact with the GalNAc lectin, and (3) Investigate the biological significance of E. histolytica proteins recruited by the GalNAc lectin to the host:parasite interface by creating """"""""knockout"""""""" mutants of these proteins using interference RNA (RNAi), antisense RNA technology, and/or expression of dominant negative mutants. Successful completion of these studies will yield a fundamental understanding of amebic proteins that interact with the E. histolytica GalNAc lectin and their role in pathogenicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI050804-02
Application #
6603149
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Coyne, Philip Edward
Project Start
2002-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$122,243
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Loving, Crystal L; Kennett, Mary; Lee, Gloria M et al. (2007) Murine aerosol challenge model of anthrax. Infect Immun 75:2689-98