Abstract

As a model for functional-biological genome analyses, Giardia provides unique perspectives on the origins of eukaryotic cells. This proposal belongs to an Interactive Research Project Grant (IRPG), which will synergize strongly with an R01 """"""""Giardia: A Model for Ancient Eukaryote Genome Analysis"""""""" (Mitchell Sogin PI, projected start date Feb. 1. 1998), whose overall goal is to obtain accurate sequence and mapping information for at least 95 percent of this small, but evolutionarily crucial genome. Our tests of inferred function of a carefully selected sample will greatly extend and validate the sequence information. The major goal unifying these biological analyses is to obtain insights into the genetic innovations that led to compartmentalization of important functions in eukaryotic cells with the following Specific Aims: The view that Giardia is """"""""pre-mitochondrial"""""""" has been challenged by our finding of three mitochondrial-like genes whose expression, location and activities we will analyze in Specific Aim 1.
In Specific Aim 2, we will gain insights into the evolution of eukaryotic endomembrane systems by analyses of three giardial protein disulfide isomerases that have both pro- and eukaryotic properties. Since the organization of genetic material is increasingly complex in eukaryotes, in Specific Aim 3, we will analyze a model region of very high transcript density to elucidate strategies that Giardia can use to efficiently exploit its limited genome size.
In Specific Aim 4, we request the capability to analyze novel genes chosen for their power to extend our understanding of the complexity of eukaryotic cellular compartments or of giardial pathogenesis. This project will provide novel insights into the evolution of basic eukaryotic cellular mechanisms, as well as specific information on an important environmentally transmitted infectious agent. It has the unique potential to reveal biological innovations reflective of the prokaryotic/eukaryotic divergence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
7R01AI042490-03
Application #
2887671
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Rubin, Fran A
Project Start
1997-09-01
Project End
2001-06-30
Budget Start
1999-09-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Oregon Health and Science University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239

  Publications

Gravett, Michael G; Jin, Ling; Pavlova, Sylvia I et al. (2012) Lactobacillus and Pediococcus species richness and relative abundance in the vagina of rhesus monkeys (Macaca mulatta). J Med Primatol 41:183-90
Adams Waldorf, K M; Rubens, C E; Gravett, M G (2011) Use of nonhuman primate models to investigate mechanisms of infection-associated preterm birth. BJOG 118:136-44
Grigsby, Peta L; Novy, Miles J; Adams Waldorf, Kristina M et al. (2010) Choriodecidual inflammation: a harbinger of the preterm labor syndrome. Reprod Sci 17:85-94
Bryant-Greenwood, G D; Yamamoto, S Y; Sadowsky, D W et al. (2009) Relaxin stimulates interleukin-6 and interleukin-8 secretion from the extraplacental chorionic cytotrophoblast. Placenta 30:599-606
Novy, Miles J; Duffy, Lynn; Axthelm, Michael K et al. (2009) Ureaplasma parvum or Mycoplasma hominis as sole pathogens cause chorioamnionitis, preterm delivery, and fetal pneumonia in rhesus macaques. Reprod Sci 16:56-70
Adams Waldorf, Kristina M; Persing, David; Novy, Miles J et al. (2008) Pretreatment with toll-like receptor 4 antagonist inhibits lipopolysaccharide-induced preterm uterine contractility, cytokines, and prostaglandins in rhesus monkeys. Reprod Sci 15:121-7
Gravett, Michael G; Adams, Kristina M; Sadowsky, Drew W et al. (2007) Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model. Am J Obstet Gynecol 197:518.e1-8
Sadowsky, Drew W; Adams, Kristina M; Gravett, Michael G et al. (2006) Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol 195:1578-89
Giannoulias, D; Haluska, G J; Gravett, M G et al. (2005) Localization of prostaglandin H synthase, prostaglandin dehydrogenase, corticotropin releasing hormone and glucocorticoid receptor in rhesus monkey fetal membranes with labor and in the presence of infection. Placenta 26:289-97
Gravett, Michael G; Novy, Miles J; Rosenfeld, Ron G et al. (2004) Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA 292:462-9

Showing the most recent 10 out of 15 publications