Project Grant 2153410

This three-year Project Grant from the National Science Foundation's Division of Molecular and Cellular Biosciences totals $1,512,792 to fund research at Louisiana State University examining the gene regulatory networks affected by purine catabolites in bacterial pathogens. The research aims to identify additional transcription factors in Burkholderia thailandensis responsive to urate and xanthine, which accumulate in host tissues during infection due to production of reactive oxygen species. Using immunoprecipitation and mass spectrometry, the project will detect protein interactions with purine ligands. In vitro and in vivo experiments will characterize DNA and ligand binding of identified transcription factors and analyze gene expression patterns and phenotypes in deletion strains. The ability of the MFTR regulatory protein to rewire these networks will also be examined. By exploring multiple proteins responsive to the same signals, the researchers intend to develop a more integrated understanding of how purine catabolites shape pathogen gene expression. This work supports the goals of the National Science Foundation's Biological Sciences program (CFDA 47.074) to advance fundamental knowledge in biology and strengthen the national research enterprise.