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Physiol. Genomics (April 14, 2009). doi:10.1152/physiolgenomics.90411.2008
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Submitted on January 9, 2009
Revised on March 3, 2009
Accepted on April 9, 2009

Lung Evolution as a Cipher for Physiology

John S. Torday1* and Virender K Rehan2

1 Harbor-UCLA Medical Center
2 Harbor UCLA Medical Center

* To whom correspondence should be addressed. E-mail: jtorday{at}labiomed.org.

In the post-genomic era, we need an algorithm to readily translate genes into physiologic principles. The failure to advance biomedicine is due to the false hope raised in the wake of the Human Genome Project by the promise of Systems Biology as a ready means of reconstructing physiology from genes. Like the atom in Physics, the cell, not the gene, is the smallest completely functional unit of biology. Trying to reassemble Gene Regulatory Networks without accounting for this fundamental feature of evolution will result in a genomic atlas, but not an algorithm for functional genomics. For example, the evolution of the lung can be 'deconvoluted' by applying cell-cell communication mechanisms to all aspects of lung biology- development, homeostasis, and regeneration/repair. Gene Regulatory Networks common to these processes predict ontogeny, phylogeny and the consequences of failed signaling. This algorithm elucidates characteristics of vertebrate physiology as a cascade of emergent and contingent cellular adaptational responses. By reducing complex physiologic traits to Gene Regulatory Networks, and arranging them hierarchically in a Self-Organizing Map, like the Periodic Table of Elements in Physics, the first principles of Physiology will emerge.







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