- B.S., Stanford University, 1975
- Ph.D., University of Wisconsin, 1987
- Postdoc., Massachusetts Institute of Technology, 1987-1992
Protein interaction/Microbial Genomics and Annotation
Multisubunit proteins are involved in every aspect of life. We use
biochemical, biophysical, genomic, and molecular genetic approaches to
identify and study protein interactions. We are studying two families
of proteins to understand how the specificity of assembly is used to
distinguish proteins with similar tertiary structures. Leucine zippers
are short alpha-helical coiled-coils that hold together the dimers in
many eukaryotic transcription factors. LysR-Type Transcriptional
Regulators (LTTRs), which form homotetramers, are one of the most
common types of bacterial transcription factors. Understanding how
leucine zippers and LTTRs form specific homo- and heterooligomers will
help us understand the principles of protein architecture and
evolution, and may allow us to develop new tools to modulate gene
We are also using a genetic approach to screen whole genomes for new oligomeric proteins and protein domains. We have identified hundreds of oligomerization domains from E. coli, the yeast Saccharomyces cerevisiae, and two important bacterial pathogens, Mycobacterium tuberculosis and Pseudomonas aeruginosa. We are using these domains to develop new approaches to functional genomics and the discovery of new antibiotics based on blocking the assembly of specific protein complexes.
Our genome-wide studies of protein interactions and E. coli proteomics have led us to appreciate the importance of continuous updating of genome annotation, We are using "new media" to build systems for the scientific community to participate in updating the annotation of every gene from any organism (but with special focus on E. coli).
EcoliWiki an be thought of as "Wikipedia for E. coli", while the Gene Ontology Normal Usage Tracking System (GONUTS) is a wiki to allow scientists to use and understand the Gene Ontology system for functional annotation.