George, Anthony - University of Technology Sydney

当前位置： X-MOL首页 › 全球导师 › 海外导师 › George, Anthony

George, Anthony Associate Professor 收藏完善纠错
University of Technology Sydney School of Life Sciences
登录后才能查看导师的联系方式，马上登录...

个人简介

Assoc Prof George has been at the University of Technology since its inception as a university in 1989. He has published over 60 papers. He graduated with a PhD degree from the University of Sydney in 1981 and completed postdoctoral fellowships at Tufts University Medical School (Boston) and the John Curtin School of Medical Research (Canberra). His tenured academic position at UTS began in 1986. His early research was focused on multidrug resistance in pathogenic bacteria and this work continued at UTS, which more recently has moved into the study of pathogenic infections in serious medical syndromes such as cystic fibrosis. A/P George’s research has taken two new directions, one beginning in 1995 and the second in 2007. In 1996, A/P George published the first and still only successful cloning, expression, and drug efflux for human P-glycoprotein in Eschericia coli. This MDR protein belongs to one of the largest gene/protein families in all species, namely ABC transporters. Most of his work since then has involved structure-function studies of ABC transporters, using traditional laboratory methods and the emerging and powerful computational molecular dynamic simulations that take X-ray crystal structures of proteins and “animate” them in computers to explore their function. We have been very successful in this field, having discovered the dimeric structural configuration of ABC transporters and elaborated a new model for the function of these proteins. A/P George’s work has been rewarded by prestigious invitations to give keynote talks at international conferences, to Chair a Gordon Research Meeting on multidrug resistance systems and invited on to the Scientific Advisory Board of the FEBS ABC Efflux Meetings, held every two years in Austria. A/P George has published trailblazing studies and many scholarly reviews in high impact journals such as Proc Natl Acad Sci USA and Trend Biochem Sci. He has supervised many Honours, Masters, and PhDs, and has a Research Associate of long standing for his mainstream ABC transporter research. Total research funding and fellowships for all projects exceeds $5m. In 2007, A/P George began a new project intended to alleviate the onset and progression of incurable asbestos-related diseases. Research began by studying the effects of asbestos fibres and counteracting agents in human lung cells; and has moved these past years to an animal model. The work has been rewarded with a Trailblazer Award (2008) and with substantial funding ($712,000) from philanthropic sources. The mouse model work has illustrated remarkable success in slowing or preventing the onset of mesothelioma, an incurable disease. A provisional patent on our new treatment has recently been converted to a full patent. Presently, we are seeking funding to take the project to a first human trial in 2017.

研究领域

1. ABC transporters and cancer ABC transporters are involved in diverse cellular processes including resistance to cytotoxic drugs. Inhibition of these proteins will improve the efficacy of primary drug treatment and render these proteins as targets for new drugs. We are using recent atomic structures as the basis for molecular dynamics calculations and cross-linking experiments designed to identify crucial mobile regions, enabling us to identify and test small molecules that interfere with the normal movement of critical regions in these proteins. [Collaboration with Dr Richard Callaghan, Oxford University; Dr Ian Kerr, Nottingham University; and Dr Megan O’Mara, QLD University]. 2. Cystic Fibrosis infections Cystic fibrosis is the most common lethal inherited disorder in Caucasians, affecting 1 in 2,500 births. Whilst median survival has increased from 1-2 years (1960) to a current 36-38 years, chronic lung disease still causes the majority of deaths associated with CF. Most patients are infected chronically with P. aeruginosa. Resistance to chemotherapeutic antibiotics is commonplace. We are testing the efficacy of the combination of tobramycin and amiloride against P. aeruginosa in clinical and laboratory studies. [in collaboration with Assoc Prof Cythia Whitworth and Dr Lynne Turnbull, IBID/UTS; and Assoc Profs Peter Middleton and Jon Iredell, Sydney University]. 3. Ameliorating Asbestosis When asbestos is mined or pulverized, it becomes suspended in the air as "parachutes", leading to inhalation into the lungs where it can induce fibrosis (asbestosis) or malignancy (mesothelioma). Asbestos fibres generate reactive oxygen radicals that cause cellular and DNA damage. We have made a serendipitous discovery for ameliorating the adverse effects of asbestos fibres that we now want to test in lung cell cultures, and then in animal trials.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Fan, X, McLaughlin, C, Ravasini, J, Robinson, C & George, AM 2018, 'Zeolite protects mice from iron-induced damage in a mouse model trial', FEBS Open Bio, vol. 8, no. 11, pp. 1773-1781.View/Download from: UTS OPUS or Publisher's site Mittra, R, Pavy, M, Subramanian, N, George, AM, O'Mara, ML, Kerr, ID & Callaghan, R 2017, 'Location of contact residues in pharmacologically distinct drug binding sites on P-glycoprotein.', Biochemical Pharmacology, vol. 123, pp. 19-28.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2017, 'How Intrinsic Dynamics Mediates the Allosteric Mechanism in the ABC Transporter Nucleotide Binding Domain Dimer.', Journal of Chemical Theory and Computation, vol. 13, no. 4, pp. 1712-1722.View/Download from: UTS OPUS or Publisher's site Cheng, YY, Mok, E, Tan, S, Leygo, C, McLaughlin, C, George, AM & Reid, G 2017, 'SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma.', Disease Markers, vol. 2017, pp. 1-11.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2016, 'Computational analysis of the MCoTI-II plant defence knottin reveals a novel intermediate conformation that facilitates trypsin binding.', Scientific Reports, vol. 6, pp. 1-10.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2015, 'The Nucleotide-Free State of the Multidrug Resistance ABC Transporter LmrA: Sulfhydryl Cross-Linking Supports a Constant Contact, Head-to-Tail Configuration of the Nucleotide-Binding Domains.', PloS one, vol. 10, no. 6, p. e0131505.View/Download from: UTS OPUS or Publisher's site Sharpe, LJ, Rao, G, Jones, PM, Glancey, E, Aleidi, SM, George, AM, Brown, AJ & Gelissen, IC 2015, 'Cholesterol sensing by the ABCG1 lipid transporter: Requirement of a CRAC motif in the final transmembrane domain', BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, vol. 1851, no. 7, pp. 956-964.View/Download from: UTS OPUS or Publisher's site George, AM & Jones, PM 2014, 'A reciprocating twin-channel model for ABC transporters', Quarterly Reviews of Biophysics, vol. 47, no. 3, pp. 189-220.View/Download from: UTS OPUS or Publisher's site George, AM & Jones, PM 2013, 'An asymmetric post-hydrolysis state of the ABC transporter ATPase dimer', PLoS One, vol. 8, no. 4.View/Download from: UTS OPUS or Publisher's site Gong, J, Luk, F, Jaiswal, R, George, AM, Grau, G & Bebawy, M 2013, 'Microparticle drug sequestration provides a parallel pathway in the acquisition of cancer drug resistance', European Journal of Pharmacology, vol. 721, no. 1-3, pp. 116-125.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2013, 'Mechanism of the ABC transporter ATPase domains: catalytic models and the biochemical and biophysical record', Critical Reviews in Biochemistry and Molecular Biology, vol. 48, no. 1, pp. 39-50.View/Download from: UTS OPUS or Publisher's site Jones, PM, Curmi, PMG, Valenzuela, SM & George, AM 2013, 'Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1', BIOMED RESEARCH INTERNATIONAL.View/Download from: UTS OPUS or Publisher's site George, AM & Jones, PM 2012, 'Perspectives on the structureefunction of ABC transporters: The Switch and Constant Contact Models', Progress in Biophysics and Molecular Biology, vol. 109, pp. 95-107.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2012, 'Role of the D-loops in allosteric control of ATP hydrolysis in an ABC transporter', Journal of Physical Chemistry A, vol. 116, no. 11, pp. 3004-3013.View/Download from: UTS OPUS or Publisher's site Nolan, LM, Croft, L, Jones, PM, George, AM, Turnbull, L, Whitchurch, CB, Beatson, SA & Mattick, JS 2012, 'Extragenic suppressor mutations that restore twitching motility to fimL mutants of Pseudomonas aeruginosa are associated with elevated intracellular cyclic AMP levels', Microbiology Open, vol. 1, no. 4, pp. 490-501.View/Download from: UTS OPUS or Publisher's site George, AM & Jones, PM 2011, 'Type II ABC permeases: Are they really so different?', Structure, vol. 19, pp. 1540-1542.View/Download from: Publisher's site Jones, PM & George, AM 2011, 'Molecular-dynamics simulations of the ATP/apo state of a multidrug ATP-binding cassette transporter provide a structural and mechanistic basis for the asymmetric occluded state', Biophysical Journal, vol. 100, no. 12, pp. 3025-3034.View/Download from: UTS OPUS or Publisher's site Jones, PM, Robinson, MW, Dalton, JP & George, AM 2011, 'The Plasmodium falciparum malaria M1 alanyl aminopeptidase (PfA-M1): Insights of catalytic mechanism and function from MD simulations', PLoS ONE, vol. 6, no. 12, p. e28589.View/Download from: UTS OPUS or Publisher's site Robinson, MW, Corvo, I, Jones, PM, George, AM, Padula, M, To, J, Cancela, M, Rinaldi, G, Tort, JF, Roche, L & Dalton, JP 2011, 'Collagenolytic Activities of the Major Secreted Cathepsin L Peptidases Involved in the Virulence of the Helminth Pathogen, Fasciola hepatica', Plos Neglected Tropical Diseases, vol. 5, no. 4, pp. 1-13.View/Download from: UTS OPUS or Publisher's site Kerr, I, Jones, PM & George, AM 2010, 'Multidrug efflux pumps: The structures of prokaryotic ATP-binding cassette transporter efflux pumps and implications for our understanding of eukaryotic P-glycoproteins and homologues.', FEBS Journal, vol. 277, no. 3, pp. 550-563.View/Download from: UTS OPUS or Publisher's site Jones, PM, O'Mara, M & George, AM 2009, 'ABC transporters: A riddle wrapped in a mystery inside an enigma', Trends in Biochemical Sciences, vol. 34, no. 10, pp. 520-531.View/Download from: UTS OPUS or Publisher's site George, AM, Jones, PM & Middleton, P 2009, 'Cystic fibrosis infections: treatment strategies and prospects', FEMS Microbiology Letters, vol. 300, no. 2, pp. 153-164.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2009, 'Opening of the ADP-bound active site in the ABC transporter ATPase dimer: Evidence for a constant contact, alternating sites model for the catalytic cycle', Proteins-Structure Function And Bioinformatics, vol. 75, no. 2, pp. 387-396.View/Download from: UTS OPUS or Publisher's site Treerat, P, Widmer, F, Middleton, P, Iredell, J & George, AM 2008, 'In vitro interactions of tobramycin with various nonantibiotics against Pseudomonas aeruginosa and Burkholderia cenocepacia', FEMS Microbiology Letters, vol. 285, no. 1, pp. 40-50.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2007, 'Nucleotide-dependent allostery within the ABC transporter ATP-binding cassette-A computational study of the MJ0796 dimer', Journal of Biological Chemistry, vol. 282, no. 31, pp. 22793-22803.View/Download from: UTS OPUS or Publisher's site Jones, PM, Turner, KM, Djordjevic, JT, Sorrell, TC, Wright, LC & George, AM 2007, 'Role of conserved active site residues in catalysis by phospholiphase B1 from Cryptococcus neoformans', Biochemistry, vol. 46, no. 35, pp. 10024-10032.View/Download from: UTS OPUS or Publisher's site George, AM & Jones, PM 2006, 'Molecular dynamics simulations and analysis of ABC transporters', Current Computer-Aided Drug Design, vol. 2, no. 3, pp. 203-214.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2005, 'Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling', International Journal For Parasitology, vol. 35, no. 5, pp. 555-566.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2004, 'The ABC transporter structure and mechanism: perspectives on recent research', Cellular and Molecular Life Sciences, vol. 61, pp. 682-699.View/Download from: UTS OPUS or Publisher's site Jones, PM & George, AM 2002, 'Mechanism of ABC transporters: a molecular dynamics simulation of a well characterised nucleotide-binding subunit', Proceedings of the National Academy of Sciences, vol. 99, no. 20, pp. 12639-12644.View/Download from: UTS OPUS George, AM & Hall, RM 2002, 'Efflux of chloramphenicol by the Cm1A1 protein', FEMS MICROBIOLOGY LETTERS, vol. 209, no. 2, pp. 209-213.View/Download from: Publisher's site George, AM & Hall, RM 2002, 'Efflux of chloramphenicol by the Cm1A1 protein', FEMS Microbiology Letter, vol. 209, no. N/A, pp. 209-213.View/Download from: UTS OPUS

我收藏的导师 >

便捷的期刊搜索 >

免费课题组网站 >

推荐链接