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Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom
Dow, Julian A. T, and Shireen A. Davies. Integrative Physiology and Functional Genomics of Epithelial Function in a Genetic Model Organism. Physiol Rev 83: 687–729, 2003; 10.1152/physrev.00035.2002.—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.
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G. M. Coast, R. J. Nachman, and D. A. Schooley An antidiuretic peptide (Tenmo-ADFb) with kinin-like diuretic activity on Malpighian tubules of the house cricket, Acheta domesticus (L.) J. Exp. Biol., November 15, 2007; 210(22): 3979 - 3989. [Abstract] [Full Text] [PDF]
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U. Rose, C. Derst, M. Wanischeck, C. Marinc, and C. Walther Properties and possible function of a hyperpolarisation-activated chloride current in Drosophila J. Exp. Biol., July 15, 2007; 210(14): 2489 - 2500. [Abstract] [Full Text] [PDF]
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J. A. T. Dow Integrative physiology, functional genomics and the phenotype gap: a guide for comparative physiologists J. Exp. Biol., May 1, 2007; 210(9): 1632 - 1640. [Abstract] [Full Text] [PDF]
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T. D. Southall, S. Terhzaz, P. Cabrero, V. R. Chintapalli, J. M. Evans, J. A. T. Dow, and S.-A. Davies Novel subcellular locations and functions for secretory pathway Ca2+/Mn2+-ATPases Physiol Genomics, September 14, 2006; 26(1): 35 - 45. [Abstract] [Full Text] [PDF]
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J. M. Evans, A. K. Allan, S. A. Davies, and J. A. T. Dow Sulphonylurea sensitivity and enriched expression implicate inward rectifier K+ channels in Drosophila melanogaster renal function J. Exp. Biol., October 1, 2005; 208(19): 3771 - 3783. [Abstract] [Full Text] [PDF]
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A. K. Allan, J. Du, S. A. Davies, and J. A. T. Dow Genome-wide survey of V-ATPase genes in Drosophila reveals a conserved renal phenotype for lethal alleles Physiol Genomics, July 14, 2005; 22(2): 128 - 138. [Abstract] [Full Text] [PDF]
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K. E. Broderick, V. Singh, S. Zhuang, A. Kambo, J. C. Chen, V. S. Sharma, R. B. Pilz, and G. R. Boss Nitric Oxide Scavenging by the Cobalamin Precursor Cobinamide J. Biol. Chem., March 11, 2005; 280(10): 8678 - 8685. [Abstract] [Full Text] [PDF]
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J. C. Radford, S. Terhzaz, P. Cabrero, S.-A. Davies, and J. A. T. Dow Functional characterisation of the Anopheles leucokinins and their cognate G-protein coupled receptor J. Exp. Biol., December 15, 2004; 207(26): 4573 - 4586. [Abstract] [Full Text] [PDF]
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V. P. Pollock, J. McGettigan, P. Cabrero, I. M. Maudlin, J. A. T. Dow, and S.-A. Davies Conservation of capa peptide-induced nitric oxide signalling in Diptera J. Exp. Biol., November 1, 2004; 207(23): 4135 - 4145. [Abstract] [Full Text] [PDF]
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K. S. Swanson, M. J. Mazur, K. Vashisht, L. A. Rund, J. E. Beever, C. M. Counter, and L. B. Schook Genomics and Clinical Medicine: Rationale for Creating and Effectively Evaluating Animal Models Experimental Biology and Medicine, October 1, 2004; 229(9): 866 - 875. [Abstract] [Full Text] [PDF]
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M. R. MacPherson, S. M. Lohmann, and S.-A. Davies Analysis of Drosophila cGMP-dependent Protein Kinases and Assessment of Their in Vivo Roles by Targeted Expression in a Renal Transporting Epithelium J. Biol. Chem., September 17, 2004; 279(38): 40026 - 40034. [Abstract] [Full Text] [PDF]
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M. G. Wheatly and Y. Gao Molecular biology of ion motive proteins in comparative models J. Exp. Biol., September 1, 2004; 207(19): 3253 - 3263. [Abstract] [Full Text] [PDF]
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P. Cabrero, V. P. Pollock, S. A. Davies, and J. A. T. Dow A conserved domain of alkaline phosphatase expression in the Malpighian tubules of dipteran insects J. Exp. Biol., September 1, 2004; 207(19): 3299 - 3305. [Abstract] [Full Text] [PDF]
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M. R. MacPherson, K. E. Broderick, S. Graham, J. P. Day, M. D. Houslay, J. A. T. Dow, and S. A. Davies The dg2 (for) gene confers a renal phenotype in Drosophila by modulation of cGMP-specific phosphodiesterase J. Exp. Biol., July 15, 2004; 207(16): 2769 - 2776. [Abstract] [Full Text] [PDF]
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K. E. Broderick, L. Kean, J. A. T. Dow, N. J. Pyne, and S. A. Davies Ectopic Expression of Bovine Type 5 Phosphodiesterase Confers a Renal Phenotype in Drosophila J. Biol. Chem., February 27, 2004; 279(9): 8159 - 8168. [Abstract] [Full Text] [PDF]
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K. W. Beyenbach Transport mechanisms of diuresis in Malpighian tubules of insects J. Exp. Biol., November 1, 2003; 206(21): 3845 - 3856. [Abstract] [Full Text] [PDF]
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K. E. Broderick, M. R. MacPherson, M. Regulski, T. Tully, J. A. T. Dow, and S. A. Davies Interactions between epithelial nitric oxide signaling and phosphodiesterase activity in Drosophila Am J Physiol Cell Physiol, November 1, 2003; 285(5): C1207 - C1218. [Abstract] [Full Text] [PDF]
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