Professor Co–Editor in Chief, GENOME
Research areas: Cytogenetics, Molecular Biology and Biochemistry
There are three main areas of interest in Dr. Hilliker’s lab: the molecular and genetic analysis of Drosophilaheterochromatin; transvection in Drosophila; and the molecular genetic analysis of oxygen defense mechanisms in Drosophila including the development of appropriate and related models of human genetic diseases in Drosophila.
Heterochromatin: constitutive heterochromatin is a ubiquitous feature of higher eukaryotic organisms. It remains condensed throughout the cell cycle, consists largely of highly-repeated sequences, and has a low gene density compared to euchromatin. Constitutive heterochromatin is difficult to sequence and many of the genes within these regions of Drosophila were not sequenced by the Drosophila genome project. Dr. Hilliker was the first to demonstrate the existence of otherwise ordinary genes in Drosophila heterochromatin and contributed to the mapping of the repeated sequences that constitute the bulk of heterochromatin in Drosophila. His laboratory is continuing to refine the genetic and molecular map of the heterochromatic regions of the Drosophila genome and to investigate further the dependency of heterochromatic genes for their location in heterochromatin for normal expression.
Transvection: transvection is a phenomenon wherein gene expression is affected by the interaction of alleles in trans and often results in partial complementation between mutant alleles. Transvection has been shown to occur at over a dozen loci in Drosophila. The unique properties that make up each transvection effect at these loci depend upon numerous factors including the somatic pairing of Drosophila interphase chromosomes, nuclear architecture, the allelic state of genes like zeste, enhancer/promoter interacting in trans, and others. Our research on transvection is focused on what this genetic phenomenon reveals about nuclear architecture and the somatic pairing of Drosophila interphase chromosomes.
Molecular Genetic Analysis of Oxygen Defense: reactive oxygen species (ROS), which have been implicated in biological aging, are produced as by-products of normal oxidative metabolism and need to be inactivated by a cell before they cause damage to DNA, proteins, and other molecules and are associated with biological aging. We have studied the mechanisms involved in the defence against ROS. We are currently focusing our efforts on six genes: quiver (qvr), a putative nueropeptide; whithered (whd), which encodes carnitine palmitoyltransferase I (CPT1), Cu Zn superoxide dismutase (SOD1); manganese superoxide dismutase; aconitase; and the Drosophila frataxin homologue. In addition to looking at the biological effects of the absence of gene activity we are also looking at the effects of tissue-specific expression in otherwise null backgrounds and the biological effects of tissue-specific overexpression in wild type backgrounds. In addition we are investigating the effects of oxidants and putative antioxidants on Drosophila lifespan and their effects on Drosophila models of human neurodegenerative genetic syndromes. Finally, we are developing Drosophila models of human genetic diseases related directly or indirectly to oxygen defense.
Leung, J.C.K., R. W. Taylor-Kamall, A.J. Hilliker and P. Reazi. Agar-polydimethysiloxane devise for quantitative investigation of oviposition behaviour of adult Drosophila melanogaster. Biomicrofluidics 9 (in press, available online). 2015.
Belozerov, V.E., S. Tarkovic, H. McNeill, A.J. Hilliker and J.C. McDermott. In vivo interaction proteomics reveal a novel p38 mitogen-activated protein kinase/Rack1 pathway regulating proteostasis in Drosophila muscle. Mol Cell Biol. 34: 474-484. 2014.
Bahadorani, S., S. Mukai, J. Rabie, J.S. Beckman, J.P. Phillips and A.J. Hilliker. Expression of zinc-deficient human SOD1 in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction. Neurobiology of Aging 34: 2322-30. 2013.
Hilliker, A.J. and R.W. Taylor-Kamall. Heterochromatin and genome size in Drosophila. Genome 56: 473-474. 2013.
Coulthard, A.B., C. Alm, I. Cealiac, D.A. Sinclair, B.M. Honda, R. Rossi, P. Dimitri and A.J. Hilliker. Essential loci in centromeric heterochromatin of Drosophila melanogaster. I: the right arm of chromosome 2. Genetics 185: 479-495. 2010.
Bahadorani, S., P. Bahadorani, E. Marcon, D.W. Walker and A.J. Hilliker. A Drosophila model of Menkes disease reveals a role for DmATP7 in copper absorption and neurodevelopment. Disease Models and Mechanisms 3: 84-91. 2010.