Dr Ruby Law - Researcher Profile

We do not have a photograph of this person yet.

Address

Department of Biochemistry & Molecular Biology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Contact Details

Email: Ruby.Law@med.monash.edu


Biography

Ruby works in the Faculty of Medicine, Nursing & Health Sciences at Monash University as a Senior Research Fellow.

Ruby Law is a biochemist and protein crystallographer.  Her research interests pertain to understanding the structure and function of large complex proteins that relate to protease biology.  Her recent work has included papers published as first author in Cell Reports, Nature, Science, Nature Structural and Molecular Biology, Blood and the Journal of Biological Chemistry.  She receives grant support from an NHMRC Program (as a sole-investigator and a Co-Investigator) as well as an NHMRC project grant (as CIA). For the past 9 years Ruby Law has held a continuing position as a Senior Researcher working alongside  ARC Federation Fellow Professor James Whisstock.

Significant recent discoveries made by Dr Law include elucidating the X-ray crystal structure of the first perforin-like protein, a bacterial protein called Plu-MACPF.  The significance of this discovery is highlighted by her joint first author publication in Science.  These data revealed the surprising finding that perforin-like immune proteins are homologous to an important mechanistically characterized family of bacterial toxins - the cholesterol dependent cytolysins (CDCs).

Dr Law recently determined the structure of murine perforin. These data revealed the surprising finding that perforin forms pores in the opposite orientation to CDCs.  This work was published as a first author paper in Nature and was the subject of a talk selected from abstracts at the Lorne Conference on Protein Structure and Function.

Dr Law has worked on the plasminogen system for a number of years and recently determined the structure of human full-length plasminogen.This work was published as a first author paper in Cell Reports.   She has determined the structure of antiplasmin (as a first author paper in Blood).  Over the past decade she has developed approaches that have finally led to her to determine the structures of activators and inhibitors of the plasminogen which is the key enzyme for the firbinolytic system.

Dr Law has supervised over many students (PhD and honours) throughout her career.  She currently manages a team of 1 postdoctoral scientist, 2 Research assistants 2 PhD students and 1 honours student.

Related Links:

Research & Supervision Interests

    Ruby Law has developed great interests in the structure and function of large complex proteins that relate to human health and diseases. Specifically, her research interests include: the fibrinolytic system,  structure and regulation of function of human glutamic decarboxylase (GAD) and, trans-membrane pore formation in perforin.

     

     

Keywords

Structure/Function (Health/Safety/Medical), X-ray crystallography, small angle Xray scattering

Qualifications

BIOCHEMISTRY AND MOLECULAR BIOLOGY
Institution: Monash University
Year awarded: 1990

Publications

Book Chapters

Zhang, Q., Law, R.H.P., Buckle, A.M., Cabrita, L., McGowan, S., Irving, J.A., Faux, N.G., Lesk, A.M., Bottomley, S.P., Whisstock, J., 2007, Serpins in Prokaryotes, in Molecular and Cellular Aspects of the Serpinopathies and Disorders in Serpin Activity, eds G.A. Silverman & D.A. Lomas, World Scientific, Singapore, pp. 131-162.

Journal Articles

Langendorf, C.G., Tuck, K.L., Key, T., Fenalti, G., Pike, R.N., Rosado, C.J., Wong, A.S., Buckle, A.M., Law, R.H.P., Whisstock, J., 2013, Structural characterization of the mechanism through which human glutamic acid decarboxylase auto-activates, Bioscience Reports [P], vol 33, issue 1, Portland Press Ltd, UK, pp. 137-149.

Linke, C., Siemens, N., Oehmcke, S., Radjainia, M., Law, R.H., Whisstock, J.C., Baker, E.N., Kreikemeyer, B., 2012, The extracellular protein factor Epf from Streptococcus pyogenes is a cell surface adhesin that binds to cells through an n-terminal domain containing a carbohydrate-binding module, Journal Of Biological Chemistry [P], vol 287, issue 45, American Society for Biochemistry and Molecular Biology, Inc., USA, pp. 38178-38189.

Law, R.H., Caradoc-Davies, T.T., Cowieson, N.P., Horvath, A.J., Quek, A.J., Amarante Da Encarnacao, J., Steer, D.L., Cowan, A.D., Zhang, Q., Lu, B.G., Pike, R.N., Smith, A.I., Coughlin, P.B., Whisstock, J.C., 2012, The x-ray crystal structure of full-length human plasminogen, Cell Reports [E], vol 1, issue 3, Cell Press, USA, pp. 185-190.

McGowan, S., Buckle, A.M., Mitchell, M.S., Hoopes, J.T., Gallagher, D.T., Heselpoth, R.D., Shen, Y., Reboul, C.F., Law, R.H., Fischetti, V.A., Whisstock, J.C., Nelson, D.C., 2012, X-ray crystal structure of the streptococcal specific phage lysin PlyC, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 109, issue 31, National Academy of Sciences, USA, pp. 12752-12757.

Lu, B.G.C., Sofian, T., Law, R.H., Coughlin, P.B., Horvath, A.J., 2011, Contribution of conserved lysine residues in the alpha{2}-antiplasmin C terminus to plasmin binding and inhibition, Journal Of Biological Chemistry [P], vol 286, issue 28, American Society for Biochemistry & Molecular Biology, Inc., USA, pp. 24544-24552.

Nogues, C., Leh, H., Langendorf, C.G., Law, R.H.P., Buckle, A.M., Buckle, M., 2010, Characterisation of peptide microarrays for studying antibody-antigen binding using surface plasmon resonance imagery, PLoS ONE [P], vol 5, issue 8 (e12152), Public Library of Science, USA, pp. 1-6.

Langendorf, C., Key, T., Fenalti, G., Kan, W., Buckle, A.M., Caradoc-Davies, T.T., Tuck, K.L., Law, R.H.P., Whisstock, J., 2010, The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions, PLoS ONE [P], vol 5, issue 2, Pubic Library of Science, USA, pp. 1-12.

Law, R.H.P., Lukoyanova, N., Voskoboinik, I., Caradoc-Davies, T.T., Baran, K., Dunstone, M.A., D'Angelo, M., Orlova, E.V., Coulibaly, F.J., Verschoor, S., Browne, K.A., Ciccone, A., Kuiper, M.J., Bird, P.I., Trapani, J.A., Saibil, H.R., Whisstock, J.C., 2010, The structural basis for membrane binding and pore formation by lymphocyte perforin, Nature [P], vol 468, issue 7322, Nature Publishing Group, UK, pp. 447-451.

Kondos, S., Hatfaludi, T.Z., Voskoboinik, I., Trapani, J.A., Law, R.H., Whisstock, J.C., Dunstone, M.A., 2010, The structure and function of mammalian membrane-attack complex/perforin-like proteins, Tissue Antigens [P], vol 76, issue 5, Wiley-Blackwell Publishing Inc, USA, pp. 341-351.

Kennan, R.M., Wong, W., Dhungyel, O., Han, X., Wong, D.M., Parker, D., Rosado, C.J., Law, R.H., McGowan, S., Reeve, S.B., Levina, V., Powers, G.A., Pike, R.N., Bottomley, S.P., Smith, A.I., Marsh, I., Whittington, R.J., Whisstock, J., Porter, C.J., Rood, J.I., 2010, The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates, Plos Pathogens [P], vol 6, issue 11, Public Library of Science, USA, pp. 1-12.

Beckham, S.A., Piedrafita, D.M., Phillips, C.I., Samarawickrema, N., Law, R.H.P., Smooker, P.M., Quinsey, N.S., Irving, J.A., Greenwood, D.L., Verhelst, S.H.L., Bogyo, M., Turk, B., Coetzer, T.H., Wijeyewickrema, L.C., Spithill, T.W., Pike, R.N., 2009, A major cathepsin B protease from the liver fluke Fasciola hepatica has atypical active site features and a potential role in the digestive tract of newly excysted juvenile parasites, International Journal of Biochemistry and Cell Biolog..., vol 41, issue 7, Pergamon, UK, pp. 1601-1612.

Estuningsih, E., Spithill, T.W., Raadsma, H., Law, R.H.P., Adiwinata, G., Meeusen, E.N.T., Piedrafita, D.M., 2009, Development and application of a fecal antigen diagnostic sandwich ELISA for estimating prevalence of fasciola gigantica in cattle in central java, Indonesia, Journal of Parasitology, vol 95, American Society of Parasitologists, USA, pp. 450-455.

Song, J., Tan, H., Mahmood, K., Law, R.H.P., Buckle, A.M., Webb, G., Akutsu, T., Whisstock, J., 2009, Prodepth: Predict residue depth by support vector regression approach from protein sequences only, PLoS ONE [P], vol 4, issue 9 (e7072), Public Library of Science, USA, pp. 1-14.

Fischer, K., Langendorf, C., Irving, J.A., Reynolds, S., Willis, C., Beckham, S.A., Law, R.H.P., Yang, S., Bashtannyk-Puhalovich, T.A., McGowan, S., Whisstock, J., Pike, R.N., Kemp, D.J., Buckle, A.M., 2009, Structural mechanisms of inactivation in scabies mite serine protease paralogues, Journal of Molecular Biology [P], vol 390, issue 4, Academic Press, UK, pp. 635-645.

Kaiserman, D., Buckle, A.M., Van Damme, P., Irving, J.A., Law, R.H.P., Matthews, A.Y., Bashtannyk-Puhalovich, T.A., Langendorf, C., Thompson, P., Vandekerckhove, J., Gevaert, K., Whisstock, J.C., Bird, P.I., 2009, Structure of granzyme C reveals an unusual mechanism of protease autoinhibition, Proceedings of the National Academy of Sciences of the United States of America, vol 106, issue 14, National Academy of Sciences, USA, pp. 5587-5592.

Zhang, Q., Law, R.H.P., Bottomley, S.P., Whisstock, J., Buckle, A.M., 2008, A structural basis for Loop C-sheet polymerization in serpins, Journal of Molecular Biology, vol 376, issue 5, Academic Press, United Kingdom, pp. 1348-1359.

Fenalti, G., Hampe, C.S., Arafat, Y., Law, R.H.P., Banga, J.P., Mackay, I.R., Whisstock, J., Buckle, A.M., Rowley, M.J., 2008, COOH-terminal clustering of autoantibody and T-cell determinants on the structure of GAD65 provide insights into the molecular basis of autoreactivity, Diabetes, vol 57, issue 5, American Diabetes Association, United States, pp. 1293-1301.

Rosado, C.J., Kondos, S., Bull, T.E., Kuiper, M., Law, R.H.P., Buckle, A.M., Voskoboinik, I., Bird, P.I., Trapani, J.A., Whisstock, J., Dunstone, M.A., 2008, The MACPF/CDC family of pore-forming toxins, Cellular Microbiology, vol 10, issue 9, Wiley-Blackwell Publishing Ltd., United Kingdom, pp. 1765-1774.

Law, R.H.P., Sofian, T., Kan, W., Horvath, A.J., Hitchen, C.R., Langendorf, C., Buckle, A.M., Whisstock, J., Coughlin, P.B., 2008, X-ray crystal structure of the fibrinolysis inhibitor alpha2-antiplasmin, Blood, vol 111, American Society of Hematology, Washington, DC, USA, pp. 2049-2052.

Rosado, C.J., Buckle, A.M., Law, R.H.P., Butcher, R.E., Kan, W., Bird, C.H., Ung, K., Browne, K.A., Baran, K., Bashtannyk-Puhalovich, T.A., Faux, N.G., Wong, W., Porter, C.J., Pike, R.N., Ellisdon, A.M., Pearce, M.C., Bottomley, S.P., Emsley, J., Smith, A.I., Rossjohn, J., Hartland, E.L., Voskoboinik, I., Trapani, J.A., Bird, P.I., Dunstone, M.A., Whisstock, J., 2007, A common fold mediates vertebrate defense and bacterial attack, Science, vol 317, issue 5844, American Association of Advancement in Science, Washington, DC, USA, pp. 1548-1551.

Fenalti, G., Law, R.H.P., Buckle, A.M., Langendorf, C., Tuck, K.L., Rosado, C.J., Faux, N.G., Mahmood, K., Hampe, C.S., Banga, J.P., Wilce, M.C.J., Schmidberger, J., Rossjohn, J., El-Kabbani, O., Pike, R.N., Smith, A.I., Mackay, I.R., Rowley, M.J., Whisstock, J., 2007, GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop, Nature Structural & Molecular Biology, vol 14, issue 4, Nature Publishing Group, New York NY USA, pp. 280-286.

Zhang, Q., Buckle, A.M., Law, R.H.P., Pearce, M.C., Cabrita, L., Lloyd, G., Irving, J.A., Smith, A.I., Ruzyla, K., Rossjohn, J., Bottomley, S.P., Whisstock, J., 2007, The N terminus of the serpin, tengpin, functions to trap the metastable native state, EMBO Reports, vol 8, issue 7, Nature Publishing Group, UK, pp. 658-663.

Law, R.H.P., Zhang, Q., McGowan, S., Buckle, A.M., Silverman, G.A., Wong, W., Rosado, C.J., Langendorf, C., Pike, R.N., Bird, P.I., Whisstock, J., 2006, An overview of the serpin superfamily, Genome Biology, vol 7, issue 5, Biomed Central Ltd, London UK, pp. 216-1-216-11.

Amin, A.A., Faux, N.G., Fenalti, G., Williams, G.N., Bernadou, A., Daglish, B., Keefe, K., Middleton, S., Rae, J., Tetis, K., Law, R.H.P., Fulton, K.F., Rossjohn, J., Whisstock, J.C., Buckle, A.M., 2006, Managing and mining protein crystallization data, Proteins: Structure Function, and Bioinformatics, vol 62, issue 1, Wiley-Liss, Hoboken USA, pp. 4-7.

Beckham, S.A., Law, R.H., Smooker, P.M., Quinsey, N.S., Caffrey, C.R., McKerrow, J.H., Pike, R.N., Spithill, T.W., 2006, Production and processing of a recombinant Fasciola hepatica cathepsin B-like enzyme (FhcatB1) reveals potential processing mechanisms in the parasite, Biological Chemistry, vol 387, issue 8, Walter de Gruyter & Co., Berlin Germany, pp. 1053-1061.

Hennebry, S.C., Law, R.H.P., Richardson, S.J., Buckle, A.M., Whisstock, J.C., 2006, The crystal structure of the transthyretin-like protein from Salmonella dublin, a prokaryote 5-hydroxyisourate hydrolase, Journal of Molecular Biology, vol 359, issue 5, Academic Press Ltd Elseiver Science Ltd, London UK, pp. 1389-1399.

Law, R.H.P., Irving, J.A., Buckle, A.M., Ruzyla, K., Buzza, M.S., Bashtannyk-Puhalovich, T.A., Beddoe, T.C., Nguyen, K., Worrall, M.D., Bottomley, S.P., Bird, P.I., Rossjohn, J., Whisstock, J.C., 2005, The high resolution crystal structure of the human tumor suppressor maspin reveals a novel conformational switch in the G-helix, Journal of Biological Chemistry, vol 280, issue 23, American Society for Biochemistry and Molecular Biology, Inc., Bethesda USA, pp. 22356-22364.

Horvath, A.J., Irving, J.A., Rossjohn, J., Law, R.H.P., Bottomley, S.P., Quinsey, N.S., Pike, R.N., Coughlin, P.B., Whisstock, J., 2005, The murine orthologue of human antichymotrypsin: a structural paradigm for CLADE A3 serpins, Journal of Biological Chemistry, vol 280, issue 52, American Society for Biochemistry and Molecular Biology, Inc., Bethesda USA, pp. 43168-43178.

Law, R.H.P., Smooker, P.M., Irving, J.A., Piedrafita, D., Ponting, R., Kennedy, N.J., Whisstock, J.C., Pike, R.N., Spithill, T.W., 2003, Cloning and expression of the major secreted cathepsin B-Iike protein from juvenile Fasciola hepatica and analysis of immunogenicity following liver fluke infection, Infection and Immunity, vol 71, issue 12, American Society for Microbiology, Washington USA, pp. 6921-6932.

Tong, J.C., Mackay, I.R., Chin, J., Law, R.H.P., Fayad, K., Rowley, M.J., 2002, Enzymatic characterization of a recombinant isoform hybrid of glutamic acid decarboxylase (rGAD67/65) expressed in yeast, Journal of Biotechnology, vol 97, issue 3, Elsevier Science BV, Amsterdam Netherlands, pp. 183-190.

Law, R., Robinson, H., Rowley, M.J., Mackay, I.R., 2001, The ubiquitous 38 kDa contaminant in glutamic acid decarboxylase preparation from the cytosol of pichia pastoris after immobilised metal ion affinity chromatography is an alcohol dehydrogenase, Biotechnology Letters, vol 23, issue 9, Kluwer Academic Publishing, Dordrecht Netherlands, pp. 697-703.

Papakonstantinou, T., Law, R.H.P., Gardiner, P., Rowley, M.J., Mackay, I.R., 2000, Comparative expression and purification of human glutamic acid decarboxylase from Saccharomyces cerevisiae and Pichia pastoris, Enzyme and Microbial Technology, vol 26 issue 9-10, Elsevier Science Inc, New York NY USA, pp. 645-652.

Law, R.H., Rowley, M.J., Mackay, I.R., Corner, B., 1998, Expression in Saccharomyces cerevisiae of antigenically and enzymatically active recombinant glutamic acid decarboxylase, Journal of Biotechnology, vol 61, Elsevier Science, Oxford UK, pp. 57-68.

Other

Sofian, T., Horvath, A.J., Law, R.H.P., Whisstock, J., 2007, Monash Researchers Fight Deep Vein Thrombosis, Media Release 13 December 2007, Monash University, Australia.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Structural and Biophysical studies of MACPF pore-forming toxins, pleurotolysin.
Supervisors:
Dunstone, M (Main), Law, H (Associate), Whisstock, J (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Structural and functional studies of plasminogen.
Supervisors:
Law, H (Joint), Whisstock, J (Joint-co).