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Principal Investigator: Dr. Yung-Fu Chang
Contact Information: E-mail: yc42@cornell.edu - Phone: 607-253-3675
Sponsor: NIH-NIAID
Grant Number: N01 AI30054
Title: C. Difficile: Genomics/Transcriptome Study
Annual Direct Cost: $312,010
Project Period: 12/01/06-11/30/09
DESCRIPTION (provided by applicant): Clostridium difficile is one of the leading causes of antibiotic-associated diarrheas in the United States and worldwide. DNA microarrays are powerful tools that allow easy genomic comparisons between different strains of the same or similar species, allowing us to compare genomic sequence of unsequenced strains with sequenced reference strains. They can also be used for transcriptional profiling, monitoring gene expression of every gene in the genome, by determining levels of transcripts. Microarrays will enhance our understanding of evolution and pathogenesis by comparing genome C. difficile strains and facilitate our understanding virulence gene expression of pathogens during infection. In this project, we propose to perform a comparative genomics study of strains isolated from different areas, hosts, and time periods and develop a microarray based on the virulence factor, mobile genetic elements, antibiotic resistance and common genes of C. difficile as our probes for diagnosis. We also propose to investigate the in vivo genes/proteins by comparing the global transcriptional and translational pattern of in vivo (pig colon loop model) and in vitro (37 and 42 C) grown C. difficile using transcriptomic and proteomic approach. The underlying rationale of global analysis of gene expression profiles at varied growth conditions in relation to pathogenicity will not only enhance the understanding of pathogenicity but also help to develop a strategy for controlling the C. difficile infection.
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