University of California, San Francisco,
Dept. of Microbiology and Immunology

Research Interests
My fundamental interest is the central biological problem of how cells regulate gene expression. My long-term goals are to decipher the circuitry of gene regulation, first in the model organism, Escherichia coli ( E. coli ), and then in other medically and environmentally relevant organisms. I have been involved in two projects whilst at UCSF.

(1) The heat shock response in E. coli results in the accumulation of unfolded proteins in both the extracytoplasm and cytoplasm. The extracytoplasmic stress response induces the transcription factor, sigma E, whilst the cytoplasmic response involves sigma 32. To further understand these responses, we have used DNA microarrays to identify target genes regulated by these sigma factors, and a combination of promoter start site mapping and DNA sequence analysis to identify target promoter elements.

(2) In a collaboration with Hao Li we present a new algorithm that extracts the binding sites for many different regulatory proteins from the regulatory regions of the E. coli genome. The algorithm used the fact that many DNA binding proteins in bacteria bind to motifs containing two short segments that are more highly conserved than the region separating them. We analyzed the locations of the predicted sites and biological functions of predicted regulons and suggested putative regulators and regulatory functions. This algorithm is applicable to many of the newly sequenced bacterial genomes.