infection worldwide and is the most prevalent parasite found in the US population. Increased transmission of I THrWichoimnonwaosmenvagicnharliosnicaisllythe eintifoelcotgeidc wagitehnt thoisf tphaeramsitoest acnodmmtohne recneont-virianlcreasexuailnly thetranpspmeaitrtaendce of drug resistant strains warrant a better understanding of the biology of this understudied organism. The !proposed study aims to provide knowledge on the biogenesis and biochemistry of an unusual organelle, the hydrogenosome, that is present in T. vaginalis, but absent in its human host. This organelle is the target of the only drug licensed for therapy for trichomonasis, metronidazole. Our previous research on hydrogenosomes has led to a series of observations that indicate common properties are shared by hydrogenosomes and mitochondria, the equivalent organelle in host cells. However, distinct differences, Iwhich might be exploited for drug design, have also been discovered. In addition to its medical importance, knowledge of the protein composition of the hydrogenosome and phylogenetic analyses of lits components should help clarify how novel cellular structures and functions were acquired in early eukaryotes and assist in understanding how energy-generating organeUes evolved in the first eukaryotic cells 2-3 billion years ago. To this end, our overall goals are to understand properties of biogenesis and Ievolution of this organelle and establish its relationship to mitochondria.
Our specific aims are: (1) To elucidate the functions of hydrogenosomal membrane proteins and examine their possible roles in organelle biogenesis;(2) To identify hydrogenosomal presequence peptidases, using biochemical and bioinformatics approaches, and compare these with mitochondrial counterparts and (3) To begin to define the proteome of T. vaginalis hydrogenosomes. These studies will increase our understanding of the biogenesis, evolution and metabolic properties of organelles in eukaryotic cells, in addition to providing important new information on a novel organelle in this parasite.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI027857-24
Application #
8242808
Study Section
Special Emphasis Panel (NSS)
Program Officer
Joy, Deirdre A
Project Start
1989-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
24
Fiscal Year
2012
Total Cost
$500,443
Indirect Cost
$175,480
Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Wexler-Cohen, Yael; Stevens, Grant C; Barnoy, Eran et al. (2014) A dynamin-related protein contributes to Trichomonas vaginalis hydrogenosomal fission. FASEB J 28:1113-21
Leitsch, David; Janssen, Brian D; Kolarich, Daniel et al. (2014) Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance. Mol Microbiol 91:198-208
Twu, Olivia; Johnson, Patricia J (2014) Parasite extracellular vesicles: mediators of intercellular communication. PLoS Pathog 10:e1004289