Integrative physiology, functional genomics and the phenotype gap: a guide for comparative physiologists.

Classical, curiosity-led comparative physiology finds itself at a crossroads. Major funding for classical physiology is becoming harder to find, as grant agencies focus on more molecular approaches or on science with more immediate strategic value to their respective countries. In turn, this shift in funding places Zoology and Animal Science departments under enormous stress: student numbers are buoyant, but how can research funding be maintained at high levels? Our research group has argued for the redefinition of integrative physiology as the investigation of gene function in an organotypic context in the intact animal. Implicit in this definition is the use of transgenics and reverse genetics to manipulate gene function in a cell-specific manner; this in turn implies the use of a genetically tractable 'model organism'. The significance of this definition is that it aligns integrative physiology with functional genomics. Again, functional genomics draws heavily on reverse genetics to elucidate the function of novel genes. The phenotype gap (the mismatch between what a genetic model organism's genome encodes and the reasons that it has historically been studied) emphasises the need to attract and empower functional biologists: can all 13,500 genes in Drosophila really be explained in terms of developmental biology? So, by embracing the integrative physiology manifesto, comparative physiologists can not only accelerate their own research, but their functional skills can make them indispensable in the post-genomic endeavour.