Integrative physiology and molecular genetics of Cell Signalling and membrane transport in Drosophila
Traditional science tends to be analytical: that is, problems are broken down into simpler parts until they become soluble. This leads to an emphasis on the powerful cellular and molecular techniques that dominate modern biology. However, this approach has limitations; if we want to integrate our detailed knowledge of individual molecules to the intact organisms, we need to take the opposite approach. Our group believes that the new, integrative, physiology demands transgenesis, and in turn genetic models. Presently, we are using the Drosophila melanogaster Malpighian (renal) tubule as an epithelial model for this new biology.
We are concentrating on transport genes that energise fluid secretion, and on the signalling genes that control epithelial function. Our understanding of renal function in Drosophila has been revolutionised by post-genomic technologies like microarrays and proteomics, and projects in our group address the function of gene families like the V-ATPases, Na+, K+ ATPases, transcription factors, channels and organic solute transporters. We are also applying the insights obtained in Drosophila to related Dipteran insects, such as the mosquitoes and tsetse flies, that are major vectors of human and animal disease.
We have shown new and important roles for the tubule in detoxification and immune response, and intriguingly have shown that the homologues of several human genes that are mutated in human renal disease are highly enriched in Drosophila tubule. This implies that the human and fly kidneys, despite 400 M years of divergent evolution, are in fact functionally rather similar.