Project Number: 1907-21000-027-00
Project Type: Appropriated

Start Date: Feb 26, 2007
End Date: Feb 25, 2012

Objective:
Identify promoters and ECF sigma factors that control expression of known and suspected virulence factors. Characterize the subset of the transcriptome related to growth in defined medium, the induction of virulence factors, and response to iron bioavailability. Elucidate mechanisms leading to iron-dependent expression of operons encoding virulence factors and regulators.

Approach:
Research will employ an interdisciplinary approach involving computational biology and laboratory methods for high-throughput functional genomics and genetics. Expression studies including the use of microarrays and high-throughput reporter screens will be used to characterize the components and behavior of virulence-related pathways, especially those related to iron homeostasis. Mutants in key regulatory proteins and gene reporter systems will be used to elucidate regulatory interactions. Computational methods will be used to identify regulatory motifs, detect statistically significant correlations in gene expression, and model selected pathways. We aggressively integrate laboratory and computational approaches to genome-scale problems in order to design and implement the most effective experiments and analytical methods.