Dr Richard Burke

• Molecular genetics of Drosophila melanogaster
• Heavy metal homeostasis
• Invertebrate developmental biology
• Animal models of human neurodegenerative diseases

1. Quantitative trait loci in heavy metal metabolism

To date, research on the metabolism of essential metals such as copper and zinc has relied on single-gene studies with candidate transport or chaperone proteins. However evidence suggests that global regulation of metals in animals relies on many interacting genes and may be a multifactorial trait. Here we will make use of an exciting new resource in Drosophila genetics, a collection of homozygous, fully genome-sequenced fly strains that are available to assay for any desired trait. We will test these fly strains for copper and zinc dietary tolerance then carry out association analyses to search for novel metal metabolism genes.

2. Genetic screen for novel zinc homeostasis genes

While two major classes of zinc transport genes have been known for several years now, relatively little is known of additional genetic factors, such as chaperone genes, that regulate cellular levels of the essential metal zinc. Here we will exploit zinc toxicity and zinc deficiency phenotypes in Drosophila, generated by the targeted genetic manipulation of zinc uptake and efflux genes, to conduct a genome-wide genetic screen for novel zinc homeostasis genes involved in the uptake, sensing, distribution or efflux of zinc.

3. The cell biology of copper transport

The function of copper transporters such as Ctr1 and ATP7 is well characterized but less is known about how these proteins are regulated at the post-transcriptional level and how the essential-yet-toxic biometal copper is distributed throughout the cell to specific organelles and compartments. We have identified a number of trafficking proteins that appear to have key roles in regulating cellular copper homeostasis and here we will investigate the function of these proteins in vivo by targeted genetic manipulation, protein cellular localization and genetic interaction studies in Drosophila.

• Lye JC, Hwang JE, Paterson D, de Jonge MD, Howard DL, Burke R.
  Detection of genetically altered copper levels in Drosophila tissues by synchrotron x-ray fluorescence microscopy. PLoS One. 2011;6(10):e26867. Epub 2011 Oct 28.
• Southon A, Greenough M, Hung YH, Norgate M, Burke R, Camakaris J.
  The ADP-ribosylation factor 1 (Arf1) is involved in regulating copper uptake. Int J Biochem Cell Biol. 2011 Jan;43(1):146-53
• Norgate M, Southon A, Greenough M, Cater M, Farlow A, Batterham P, Bush AI, Subramaniam VN, Burke R, Camakaris J.
  Syntaxin 5 is required for copper homeostasis in Drosophila and mammals. PLoS One. 2010 Dec 20;5(12):e14303
• Binks T, Lye JC, Camakaris J, Burke R
  Tissue-specific interplay between copper uptake and efflux in Drosophila. J Biol Inorg Chem 2010 May;15(4):621-8.
• Southon A, Palstra N, Veldhuis N, Gaeth A, Robin C, Burke R, Camakaris J
  Conservation of copper-transporting P(IB)-type ATPase function. Biometals. 2010 Aug;23(4):681-94.
• Sanokawa-Akakura R, Cao W, Allan K, Patel K, Ganesh A, Heiman G, Burke R, Kemp FW, Bogden JD, Camakaris J, Birge RB, Konsolaki M
  Control of Alzheimer's amyloid beta toxicity by the high molecular weight immunophilin FKBP52 and copper homeostasis in Drosophila. PLoS One. 2010 Jan 13;5(1):e8626
• Burke R, Commons E, Camakaris J
  Expression and Localisation of the Essential Copper Transporter DmATP7 in Drosophila Neuronal and Intestinal Tissues. Int J Biochem Cell Biol. 2008. 40(9):1850-1860
• Southon A, Farlow A, Norgate M, Burke R, Camakaris J
  Malvolio is a copper transporter in Drosophila melanogaster. J Exp Biol. 2008. Mar; 211(5):709- 16.
• Norgate M, Lee E, Southon A, Farlow A, Batterham P, Camakaris J, Burke R.
  Essential Roles in Development and Pigmentation for the Drosophila Copper Transporter DmATP7. Mol Biol Cell. 2006 Jan;17(1):475-84.;
• Southon A*, Burke R*, Norgate M, Batterham P, Camakaris J.
  Copper Homeostasis in Drosophila melanogaster S2 cells Biochem J. 2004 Oct 15;383(Pt 2):303-9. *Authors contributed equally to this publication
• Burke R, Nellen D, Bellotto M, Hafen E, Senti KA, Dickson BJ, Basler K.
  Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Cell. 1999 Dec 23;99(7):803-15.
• Burke R, Basler K.
  Hedgehog signaling in Drosophila eye and limb development - conserved machinery, divergent roles? Current Opinion in Neurobiology (1997) 7(1):55-61.
• Burke R, Basler K.
  Dpp receptors are autonomously required for cell proliferation in the entire developing Drosophila wing. Development (1996) 122(7):2261-9.
• Burke R, Basler K.
  Hedgehog-dependent patterning in the Drosophila eye can occur in the absence of Dpp signaling. Developmental Biology (1996 ) 179(2):360-8.
• Nellen D, Burke R, Struhl G, Basler K.
  Direct and long-range action of a Dpp morphogen gradient. Cell (1996) 85(3):357-68.