Deciphering the Genomic Rosetta Stone

Abstract:
Learning to sequence the genomic material of living organisms can be likened to the use of telescopes to uncover the history of the universe. As of today, the NIH Databases report roughly 10^17 nucleotides of genomic information. But how well do we really understand the meaning of those nucleotides? Even in arguably one of biology’s best understood organisms, the humble bacterium E. coli, for more than 60% of its genes we have no idea if or how they are regulated. The situation is even more grim with other celebrated model organisms, never mind something exotic such as a deep sea angler fish or an orca. In this talk, I will describe a strategy to overcome this regulatory ignorance. Specifically, I will show how using a combination of tools from modern molecular biology, we can go from complete regulatory ignorance of some promoter of interest to a knowledge of both binding sites and the identity of the transcription factors that bind them. But then what? The second part of my talk will focus on how using the tools of statistical physics we can predict the input-output properties of these newly discovered regulatory architectures. In the spirit of little steps for little feet, I will show a thorough quantitative dissection of two of the most abundant regulatory motifs in E. coli, the simple repression architecture and the simple activation architecture, illustrating how to construct a theory-experiment dialogue in the study of gene regulation.