Finding needles in genomic haystacks
Van Leeuwenhoek Lecture on BioScience.
Rob Phillips is a Fred and Nancy Morris Professor of Biophysics and Biology at Caltech, Pasadena. Prior to the great fun of a life in science, he spent 7 years of travel, self-study and work as an electrician. He did his B.S. at the University of Minnesota, his PhD at Washington University (1989). His research interests are the physical biology of the cell, models of transcription and active matter, physical genomes and biophysical approaches to evolution. He is the author of several books, among which The Physical Biology of the Cell (2012). He is engaged in the publication of a couple of new books, one about the statistical mechanics of cell signaling, another one about the quantitative view of gene expression.
The ability to read the DNA sequences of different organisms has transformed biology in much the same way that the telescope transformed astronomy. And yet, much of the sequence found in these genomes is as enigmatic as the Rosetta stone was to early Egyptologists. Even in what is arguably biology's best understood organism, for well over half the genes we have no idea how they are regulated. I will describe unexpected ways developed in a Princeton University PhD thesis of using the physics of information transfer first developed at Bell Labs for thinking about telephone communications to try to decipher the meaning of the enigmatic regulatory features of genomes. Specifically, I will show how we have been able to explore genes for which we know nothing about how they are regulated by using a combination of mutagenesis, deep sequencing and the physics of information, with the result that we have now falsifiable hypotheses about how these genes work. With hypotheses about how these regulatory architectures work in hand, I will then show how the tools of statistical physics can be used to make polarizing predictions about regulatory function and the corresponding physiological and evolutionary adaptations they permit.