DNA and proteins work together to bring the genome to life, cooperating to carry out essential processes such as transcription, replication, recombination, and DNA repair. Ultimately, these processes are regulated by modulating just two properties of DNA-dependent enzymes: the level of their activity, and where they act. My laboratory is interested in investigating the second part of this equation: how and where proteins interact with the genome on a global scale in vivo, and how these interactions affect the biology of living cells. In particular, we ask:

(1) What rules do DNA-associated proteins use to bind their genomic targets in vivo?

(2) How are protein-genome interactions regulated so they occur at the proper time, and in the proper tissues?

(3) What are the functional consequences of protein-genome interactions, especially with regard to specifying transcriptional programs?

We aim to answer these questions using the yeast S. cerevisiae, the most experimentally tractable eukaryote, and the nematode C. elegans, one of the simplest metazoans. We rely heavily on the complete genome sequences of both organisms, their rich history of genetic studies, and the latest genomic and molecular techniques. One of the most important tools used in the laboratory is the DNA microarray, a simple but powerful new research tool that can be used to track the level of every RNA message in a cell, and at the same time create high-resolution, genome-wide maps of protein-DNA interactions.