The Victor Chang Cardiac Research Institute is an independent, not-for-profit research facility, based in Darlinghurst, New South Wales, Australia. The Institute was founded in memory of pioneering cardiac surgeon Dr. Victor Chang and his passionate belief in the power of discovery.Established on 15 February 1994, approximately three years after Dr. Chang's death, and opened by then Prime Minister Paul Keating, the Institute has become a world-class research and research training facility. Wikipedia.
News Article | March 22, 2017
Laboratory Design (LD): How did you get into your field? David Keenan (DK): In an un-conventional way. I studied Zoology at University in the U.K., after which I joined a wine company that sent me to Edinburgh. After a couple of years, I realized I wanted to get back into science and found myself at the Medical Research Council’s Human Genetics Unit in Edinburgh working in a lab looking into the genetic disorders of muscle disease. The lab was successful and my boss was recruited to Sydney. He invited me to join him, so I left the U.K. to move to Australia, where I took on the role of setting up the lab and aquarium at the Victor Chang Cardiac Research Institute in Sydney. I thoroughly enjoyed this and it led to my next job, at the Garvan Institute. Over time I became responsible for planning and delivering larger and larger research buildings. My last project was the Victorian Comprehensive Cancer Center, a large $1 billion Public Private Partnership mixed health and research facility in Melbourne. I’ve now found my way to HDR. LD: What’s the most surprising thing you’ve learned in your career? DK: How close many door frames are to the height of a ULT-80 freezer, or how wide a double door is for a pallet movement/large piece of equipment. It is important to consider the items moving through any given door and, in particular, the full travel path for some large items to ensure usefulness and flexibility of the space. LD: What’s a common mistake made by those working on designing/constructing a laboratory? DK: The movement of materials and people through a lab is often not considered fully or in all situations. I’ve seen ramps in places where heavy loads are moved, or a single elevator at one end of a building that might often be on exclusive use. Then there are the issues of moving biological materials through non-lab environments to get from point A to B: Do you wear gloves or not, gowns or not; double-bag or not; are you traversing where people might eat/drink; and so on. These are all issues to be carefully considered in planning out how the spaces will be used. LD: What do you consider the highlight of your career? DK: It’s a tough pick but the Kinghorn Cancer Centre is a beautiful facility that is planned to be both functionally simple and, in my opinion, ‘elegant.’ The Victorian Comprehensive Cancer Centre is a close second for the sheer scale and challenge—everything about it was big! LD: If you could give just one piece of advice to others in your field, what would it be? LD: Can you describe a funny or exciting moment in your career? DK: A very exciting AND scary moment in my career had to be when we unveiled the Richard Long (U.K. Turner Prize-winning artist) artwork in the Kinghorn Cancer Centre. The artwork is a chalk mix on painted concrete that is eight stories high: spectacular in both scale and impact. There was a heart-stopping moment when a leak appeared during a freak torrential storm immediately after occupancy. Water tracked to just above the piece and began to run down the middle of the artwork … thankfully we repaired the leak immediately and the art wasn’t damaged but it was a scary time! LD: Is there anything else you’d like to share with the readers of Laboratory Design? DK: Don’t take yourself too seriously.
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2011.2.2.1-2 | Award Amount: 17.04M | Year: 2012
NEURINOX aims at elucidating the role of NADPH oxidases (NOX) in neuroinflammation and its progression to neurodegenerative diseases (ND), as well as evaluating the potential of novel ND therapeutics approaches targeting NOX activity. NOX generate reactive oxygen species (ROS) and have emerged as regulators of neuroinflammation. Their role is complex: ROS generated by NOX lead to tissue damage in microglia-mediated neuroinflammation, as seen in amyotrophic lateral sclerosis (ALS), while absence of ROS generation enhances the severity of autoimmune-mediated neuroinflammation, as seen for e.g. in multiple sclerosis (MS). The objective of the 5 years NEURINOX project is to understand how NOX controls neuroinflammation, identify novel molecular pathways and oxidative biomarkers involved in NOX-dependent neuroinflammation, and develop specific therapies based on NOX modulation. The scientific approach will be to: (i) identify NOX-dependent molecular mechanisms using dedicated ND animal models (ii) develop therapeutic small molecules either inhibiting or activating NOX and test their effects in animal models (iii) test the validity of identified molecular pathways in clinical studies in ALS and MS patients. NEURINOX will contribute to better understand brain dysfunction, and more particularly the link between neuroinflammation and ND and to identify new therapeutic targets for ND. A successful demonstration of the benefits of NOX modulating drugs in ALS and MS animal models, and in ALS early clinical trials will validate a novel high potential therapeutics target for ALS and also many types of ND. NEURINOX has hence a strong potential for more efficient ND healthcare for patients and thus for reducing ND healthcare costs. This multi-disciplinary consortium includes leading scientists in NOX research, ROS biology, drug development SMEs, experts in the neuroinflammatory aspects of ND, genomics and proteomics, and clinicians able to translate the basic science to the patient.
Martinac B.,Victor Chang Cardiac Research Institute |
Martinac B.,University of New South Wales
Biochimica et Biophysica Acta - Biomembranes | Year: 2014
As biological force-sensing systems mechanosensitive (MS) ion channels present the best example of coupling molecular dynamics of membrane proteins to the mechanics of the surrounding cell membrane. In animal cells MS channels have over the past two decades been very much in focus of mechanotransduction research. In recent years this helped to raise awareness of basic and medical researchers about the role that abnormal MS channels may play in the pathophysiology of diseases, such as cardiac hypertrophy, atrial fibrillation, muscular dystrophy or polycystic kidney disease. To date a large number of MS channels from organisms of diverse phylogenetic origins have been identified at the molecular level; however, the structure of only few of them has been determined. Although their function has extensively been studied in a great variety of cells and tissues by different experimental approaches it is, with exception of bacterial MS channels, very little known about how these channels sense mechanical force and which cellular components may contribute to their function. By focusing on MS channels found in animal cells this article discusses the ways in which the connections between cytoskeleton and ion channels may contribute to mechanosensory transduction in these cells. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. This article is part of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and membrane channels, receptors and transporters. Guest Editor: Jean Claude Hervé. © 2013 Elsevier B.V.
Del Monte G.,Victor Chang Cardiac Research Institute |
Harvey R.P.,Victor Chang Cardiac Research Institute |
Harvey R.P.,University of New South Wales
Cell | Year: 2012
Despite the profound impact of coronary artery disease on human health, the origins of the coronary blood vessels are poorly understood. Wu et al. use imaging and genetic techniques to show that the endocardium contributes to the coronary vessels and that the coronary arteries and veins have multilineage origins. © 2012 Elsevier Inc.
Yeda Research, Development Co. and Victor Chang Cardiac Research Institute | Date: 2016-05-05
A method of potentiating cardiac regeneration with neuregulin treatment in a subject in need thereof. The method comprising administering to the subject a therapeutic effective amount of an agent which upregulates activity or expression of ErbB-2, thereby potentiating cardiac regeneration with neuregulin treatment.
Kikuchi K.,Victor Chang Cardiac Research Institute |
Poss K.D.,Howard Hughes Medical Institute
Annual Review of Cell and Developmental Biology | Year: 2012
The heart holds the monumental yet monotonous task of maintaining circulation. Although cardiac function is critical to other organs and to life itself, mammals are not equipped with significant natural capacity to replace heart muscle that has been lost by injury. This deficiency plays a role in leaving millions worldwide vulnerable to heart failure each year. By contrast, certain other vertebrate species such as zebrafish are strikingly good at heart regeneration. A cellular and molecular understanding of endogenous regenerative mechanisms and advances in methodology to transplant cells together project a future in which cardiac muscle regeneration can be therapeutically stimulated in injured human hearts. This review focuses on what has been discovered recently about cardiac regenerative capacity and how natural mechanisms of heart regeneration in model systems are stimulated and maintained. Copyright © 2012 by Annual Reviews. All rights reserved.
Cropley J.E.,Victor Chang Cardiac Research Institute
Proceedings. Biological sciences / The Royal Society | Year: 2012
Natural selection acts on variation that is typically assumed to be genetic in origin. But epigenetic mechanisms, which are interposed between the genome and its environment, can create diversity independently of genetic variation. Epigenetic states can respond to environmental cues, and can be heritable, thus providing a means by which environmentally responsive phenotypes might be selectable independent of genotype. Here, we have tested the possibility that environment and selection can act together to increase the penetrance of an epigenetically determined phenotype. We used isogenic A(vy) mice, in which the epigenetic state of the A(vy) allele is sensitive to dietary methyl donors. By combining methyl donor supplementation with selection for a silent A(vy) allele, we progressively increased the prevalence of the associated phenotype in the population over five generations. After withdrawal of the dietary supplement, the shift persisted for one generation but was lost in subsequent generations. Our data provide the first demonstration that selection for a purely epigenetic trait can result in cumulative germline effects in mammals. These results present an alternative to the paradigm that natural selection acts only on genetic variation, and suggest that epigenetic changes could underlie rapid adaptation of species in response to natural environmental fluctuations.
Vandenberg J.I.,Victor Chang Cardiac Research Institute
Physiological reviews | Year: 2012
The human ether-a-go-go related gene (hERG) encodes the pore-forming subunit of the rapid component of the delayed rectifier K(+) channel, Kv11.1, which are expressed in the heart, various brain regions, smooth muscle cells, endocrine cells, and a wide range of tumor cell lines. However, it is the role that Kv11.1 channels play in the heart that has been best characterized, for two main reasons. First, it is the gene product involved in chromosome 7-associated long QT syndrome (LQTS), an inherited disorder associated with a markedly increased risk of ventricular arrhythmias and sudden cardiac death. Second, blockade of Kv11.1, by a wide range of prescription medications, causes drug-induced QT prolongation with an increase in risk of sudden cardiac arrest. In the first part of this review, the properties of Kv11.1 channels, including biogenesis, trafficking, gating, and pharmacology are discussed, while the second part focuses on the pathophysiology of Kv11.1 channels.
Hynson R.M.G.,Victor Chang Cardiac Research Institute
Nature Structural and Molecular Biology | Year: 2016
Large protein complexes assemble spontaneously, yet their subunits do not prematurely form unwanted aggregates. This paradox is epitomized in the bacterial flagellar motor, a sophisticated rotary motor and sensory switch consisting of hundreds of subunits. Here we demonstrate that Escherichia coli FliG, one of the earliest-assembling flagellar motor proteins, forms ordered ring structures via domain-swap polymerization, which in other proteins has been associated with uncontrolled and deleterious protein aggregation. Solution structural data, in combination with in vivo biochemical cross-linking experiments and evolutionary covariance analysis, revealed that FliG exists predominantly as a monomer in solution but only as domain-swapped polymers in assembled flagellar motors. We propose a general structural and thermodynamic model for self-assembly, in which a structural template controls assembly and shapes polymer formation into rings. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
Fatkin D.,Victor Chang Cardiac Research Institute
Cold Spring Harbor perspectives in medicine | Year: 2014
Cardiomyopathies are a heterogeneous group of heart muscle diseases associated with heart failure, arrhythmias, and death. Genetic variation has a critical role in the pathogenesis of cardiomyopathies, and numerous single-gene mutations have been associated with distinctive cardiomyopathy phenotypes. Contemporaneously with these discoveries, there has been enormous growth of genome-wide sequencing studies in large populations, data that show extensive genomic variation within every individual. The considerable allelic diversity in cardiomyopathy genes and in genes predicted to impact clinical expression of disease mutations indicates the need for a more nuanced interpretation of single-gene mutation in cardiomyopathies. These findings highlight the need to find new ways to interpret the functional significance of suites of genetic variants, as well as the need for new disease models that take global genetic variant burdens, epigenetic factors, and cardiac environmental factors into account.