in the post genome-closure era

Future: Protein kinases and cyberbiology
As the human and mouse genome projects begin to see closure, we anticipate a new era in biology in which the majority of the ~70,000 mammalian genes are known, either as physical segments fully cloned, mapped, and sequenced or as family members known by partial molecular characterization. Nobel laureate Arno Penzias has pointed out that in many areas of science, information has accumulated at such a rapid rate that the real challenge becomes the management and integration of information rather than data collection itself. One of the most startling findings of genetics is the conservation of signaling pathways during evolution. The onus of biologists in the era of a closing frontier of genome science thus becomes the problem of working out the logic of conserved cellular signaling pathways. Such an intellectual approach to biology was first sketched 50 years ago by Norbert Wiener (photo at top left of this page) in his pioneering 1948 treatise "Cybernetics, or Control and Communication in the Animal and the Machine". Wiener proposed a mathematical treatment of life processes as control circuitry in which cellular elements (gene products) interact in a logical network featuring stimulatory and inhibitory (feedback) circuitry. In these conserved pathways, gene products often exert their stimulatory or inhibitory effect on neighboring gene products in the pathway through physical interactions involving complementarity of protein surfaces between "interactors", such as the tight interaction between the SH2 domains of signaling effectors with specific phosphotyrosines on other signaling effectors, such as the receptor tyrosine kinases (RTKs).

Twentifirst century biology in the paradigm of physics: cellular signaling "cyberbiology"
We envision a new era in biology post-genome closure that departing substantially in methodology and approach from the present fishing expedition era to the point where post-closure biology will more resemble physics in the 1930s: mathematical modeling to provide biologists an opportunity to return to the wet bench only to measure rate constants defining the logic of cellular signaling. We hope to anticipate this new "cyberbiology" meshing Wiener's cybernetics with genetic tools by concentrating our focus on the dissection of those evolutionarily-conserved cellular signaling pathways which integrate paracrine communication between cells in a tissue with reprogramming events in the cell nucleus.
We are keenly interested in the regenerative processes in adult skeletal muscle, which offer an inroad to muscle replacement after inborn (dystrophin) or acquired damage.

"IT IS KNOWN THAT NATURE WORKS CONSTANTLY WITH THE SAME MATERIALS. SHE IS INGENIOUS TO VARY ONLY THE FORMS."
--E. Geoffroy Saint-Hilaire, 1807

• Norbert Perrimon who suggested to me more than a decade ago when I was at the Center for Blood Research in Boston, that cross-genera thinking would be necessary to work out signal transduction pathways, because their logic tends to be conserved during evolution.
• Craig Giroux who reminded me about Norbert Wiener when I came to him last December looking for ideas for a lecture in MBG 740 ("Cellular Signaling") about the logic (not the molecules) of cellular signaling
• John Gerhart, who led me to the 1896 edition of E. B. Wilson's "The Cell in Development and Heredity" while I was studying for my oral Ph.D. qualifying exam at UC-Berkeley
• Markku Kurkinen who gave the 190-year-old quotation from Saint-Hilaire.
• Eric Davidson and Rob Maxson, who provided me with the faith 20 years that mathematical modeling of biological phenomena might help to focus wet-bench inquiry (a passion that lay dormant for awhile)