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Copper homeostasis gene discovery in Drosophila melanogaster

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Abstract

Recent studies have shown a high level of conservation between Drosophila melanogaster and mammalian copper homeostasis mechanisms. These studies have also demonstrated the efficiency with which this species can be used to characterize novel genes, at both the cellular and whole organism level. As a versatile and inexpensive model organism, Drosophila is also particularly useful for gene discovery applications and thus has the potential to be extremely useful in identifying novel copper homeostasis genes and putative disease genes. In order to assess the suitability of Drosophila for this purpose, three screening approaches have been investigated. These include an analysis of the global transcriptional response to copper in both adult flies and an embryonic cell line using DNA microarray analysis. Two mutagenesis-based screens were also utilized. Several candidate copper homeostasis genes have been identified through this work. In addition, the results of each screen were carefully analyzed to identify any factors influencing efficiency and sensitivity. These are discussed here with the aim of maximizing the efficiency of future screens and the most suitable approaches are outlined. Building on this information, there is great potential for the further use of Drosophila for copper homeostasis gene discovery.

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Acknowledgments

The authors would like to thank Donald Ingram for generous support with paraquat microarrays and Ben Ong for support with copper microarrays. We are also grateful to John Roote for supplying the deficiency mutants used in mapping the Syx5 region and to John Damiano, Louise Williams, Phoebe Heard, and Sally Coutts who assisted with the various screens. We thank Dr. Richard Burke for helpful discussions. Part of this work was supported by the Intramural Research Program of the NIH, National Institute on Aging (SZ) and grants from the International Copper Association (JC and PB), the Australian Research Council (JC), and the Australian Institute of Nuclear Science and Engineering (JC).

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Authors and Affiliations

  1. Department of Genetics, The University of Melbourne, Parkville, VIC, 3010, Australia

    Melanie Norgate, Adam Southon, Phil Batterham & James Camakaris

  2. Centre for Environmental Stress and Adaptation Research, The University of Melbourne, Parkville, VIC , 3010, Australia

    Phil Batterham

  3. Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, 6200 Seaforth Street, Baltimore, MD, 21224, USA

    Sige Zou

  4. Bioinformatics Unit, Research Resources Branch, National Institute on Aging, 6200 Seaforth Street, Baltimore, MD, 21224, USA

    Ming Zhan & Yu Sun

Authors
  1. Melanie Norgate
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  2. Adam Southon
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  3. Sige Zou
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  4. Ming Zhan
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  5. Yu Sun
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  6. Phil Batterham
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  7. James Camakaris
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Correspondence to James Camakaris.

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Norgate, M., Southon, A., Zou, S. et al. Copper homeostasis gene discovery in Drosophila melanogaster . Biometals 20, 683–697 (2007). https://doi.org/10.1007/s10534-006-9075-2

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