Integrative physiology and functional genomics of epithelial function in a genetic model organism.

Classically, biologists try to understand their complex systems by simplifying them to a level where the problem is tractable, typically moving from whole animal and organ-level biology to the immensely powerful "cellular" and "molecular" approaches. However, the limitations of this reductionist approach are becoming apparent, leading to calls for a new, "integrative" physiology. Rather than use the term as a rallying cry for classical organismal physiology, we have defined it as the study of how gene products integrate into the function of whole tissues and intact organisms. From this viewpoint, the convergence between integrative physiology and functional genomics becomes clear; both seek to understand gene function in an organismal context, and both draw heavily on transgenics and genetics in genetic models to achieve their goal. This convergence between historically divergent fields provides powerful leverage to those physiologists who can phrase their research questions in a particular way. In particular, the use of appropriate genetic model organisms provides a wealth of technologies (of which microarrays and knock-outs are but two) that allow a new precision in physiological analysis. We illustrate this approach with an epithelial model system, the Malpighian (renal) tubule of Drosophila melanogaster. With the use of the beautiful genetic tools and extensive genomic resources characteristic of this genetic model, it has been possible to gain unique insights into the structure, function, and control of epithelia.