Perusing the summary of these two books will give you an indication of our general interests.

A Genetic Switch

This third edition of A Genetic Switch (2004, Cold Spring Harbor Laboratory Press) comprises a re-print of the first four chapters of the original plus a new chapter that describes recent significant advances. The book describes in basic terms the growth of the bacterial virus lambda. Three chapters describe the processes of gene regulation in lambda and show how they provide a paradigm for gene regulation in development in higher organisms. A fourth chapter outlines the experimental bases of the major conclusions. The new fifth chapter describes, among other things, how, at crystallographic resolution, simple binding interactions between proteins binding to DNA underlies gene activation and, as well, the cooperative binding of regulatory proteins to widely separated DNA sites. The figures from this book are available on the Web site www.genesandsignals.org, and three lectures based on this book and delivered at The Rockefeller University in February, 2005, are available on video on our Web site.

Genes and Signals

What distinguishes a man from a mouse is not so much different proteins, but rather the appearance (or disappearance) of common proteins at different times and positions in the developing (and fully formed) organisms. And very often these and other organisms use similar signals, sent from one cell to another, to determine those patterns. In response to such signals, specific genes are transcribed or repressed, proteins degraded or stabilized, RNA transcripts spliced one way or another, and so on. These are examples of ’regulatory’ decisions.

Genes and Signals (Ptashne, M and Gann, A, 2002, Cold Spring Harbor Laboratory Press) ) argues that a rather simple mechanism - recruitment, also called cooperative binding - lies at the heart of many regulatory decisions. The mechanism — to which alternatives can be found, at least in bacteria — was widely exploited by evolution for at least two reasons. First, the mechanism ready lends itself to producing new and additional ’meanings’ to signals; and second, because it allows step-wise improvements and ’add ons’ to each regulatory process. There is a price, however: the regulatory world, governed by ’Mass Action,’ is prone to error, and complexity of a certain sort is required to make it work reliably. The Web site www.genesandsignals.org makes available all the figures from the book, as well as four lectures based on the book delivered by Ptashne at The Rockefeller University in January 2002.