The overall goal of this project is to determine the molecular basis of Campylobacter-induced abortion using various functional genomic approaches.
The specific objectives are: <Ol> <LI> To perform comparative genomics to identify the genetic markers specific for abortion.<LI> To examine the transcriptome polymorphisms between abortifacient and non-abortifacient C. jejuni strains and determine the global gene expression profiles of C. jejuni during abortion. <LI> To identify abortion-specific proteins and antigens by using proteomics and immunoproteomics.<LI> To define the functions of selected genes in causing abortion using gene-specific mutagenesis in conjunction with the guinea pig model of ovine abortion.</ol>
This study is a collaborative effort by multiple investigators with expertise in veterinary microbiology, biostatics, and veterinary pathology. Fundamental research will be conducted using computational and experimental approaches. Postdoctoral researchers and graduate students will be trained with advanced knowledge in functional genomics. New information on how Campylobacter causes abortion in sheep will be gained from the research activities.
NON-TECHNICAL SUMMARY: Abortion of pregnant ewes is a significant disease problem and results in considerable economic loss to sheep producers. Campylobacter is one of the most frequent infectious causes of sheep abortion worldwide. Our recent work indicates that a highly virulent Campylobacter jejuni clone (named SA for sheep abortion) has emerged as the predominant cause of ovine abortion outbreaks in the U.S. How this newly emerged clone causes sheep abortion is unknown. To facilitate the control of this important disease, we have recently determined the complete genomic sequence of clone SA, providing a unique opportunity for us to study Campylobacter-associate abortion at the molecular and genomic levels. In this project, we will perform large-scale functional analysis of genomic sequences of clone SA using various approaches including in silico comparative genomics, comparative genomic hybridization, global transcriptome analysis (in vitro and in vivo), proteomics/immunoproteomics, gene-specific mutagenesis, and animal studies. Upon completion, we will be able to understand why this clone is highly virulent to pregnant ewes and how it causes abortion. The findings will potentially identify novel candidates for the development of diagnostic tools and protective vaccines against Campylobacter. The outcomes will directly benefit U.S. sheep production and also positively impact food safety because Campylobacter jejuni is also a major foodborne human pathogen.
APPROACH: Various genomic approaches will be utilized in this study. These include in silico comparative genomics, microarray-based comparative genomic hybridization, microarray-based global transcriptome analysis (in vitro and in vivo), proteomics/immunoproteomics, gene-specific mutagenesis, and animal model systems.