Genetics - Theses
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ItemA genetic investigation of copper deficiency using Drosophila melanogaster(University of Melbourne, 2008)The phenotypic consequences of copper deficiency are serious and include cardiopathy and neurological dysfunction. These are complex traits that belie simple responsive biomarkers. At present, there are no robust biomarkers for copper deficiency within the human population. This has implications for setting the Recommended Daily Intake (RDI) that will protect most of the population from the consequences of copper deficiency, which various measures place between 0.9mg of copper per day and 3.0mg/day for adult males. The best information available on the copper content of Western diets places a significant proportion of the population below all current RDIs. This incongruity suggests that marginal copper deficiency may be more prevalent than is currently appreciated. Due to the lack of informative biomarkers and the complexity of outcomes in Man, it is appropriate to interrogate the genetics of copper deficiency in order to identify its phenotypic consequences in more tractable model systems, such as Drosophila melanogaster. The aim-set of this investigation is to (1) experimentally generate copper deficiency in Drosophila melanogaster, (2) identify and characterise the phenotypic outcomes of this copper deficiency and (3) identify novel genetic components that respond to copper deficiency. This investigation has identified that the genetic manipulation of DmATP7 elicits a functional copper deficiency. The phenotypic consequences of this are a disruption to development and an adult hypopigmentation of the cuticle. This altered pigmentation has been defined as a valuable indicator of copper status within the fly, and has formed the basis of a forward genetic screen. Malvolio has been identified as an important and functional copper transporter in Drosophila. The significance of this transporter to copper homeostasis, immunity and neuronal function in both insects and humans is considered. This thesis hopes to advance the paradigm of copper homeostasis in Drosophila with the aim of developing a robust definition of copper deficiency within the complex milieu of zinc and iron homeostasis.