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- Blanchard, H
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Dr. Helen Blanchard completed her Ph.D in chemical crystallography in 1990 at Queen Mary College, The University of London, UK under the guidance of Professor Michael Hursthouse. She then gained research experience in protein X-ray crystallography in Canada (1991-1996) within the laboratory of Professor Michael James at the University of Alberta, Edmonton, and subsequently Associate Professor Mirek Cygler at the Biotechnology Research Institute, National Research Council of Canada, in Montreal.
From 1997 until 2002 she worked at the University of California San Diego (UCSD), the University of Zurich with Professor Markus Grütter, St Vincent’s Institute of Medical Research in Melbourne, the University of Queensland, and in industry with Morphochem AG in Basel, Switzerland.
The research that Dr. Blanchard engaged in until 2002 was focused in structural biology mainly within the protease research field, has been published in Nature, Nature Structural Biology, and Structure, and included the first structural information informing on the mechanism of function of the calpain system and that of caspase-8 which was the first structure of an initiator enzyme of apoptosis. This work and subsequent work led to her admission (2006) as Fellow of the Royal Society of Chemistry as recognition of contributions to structural biology and chemistry research.
In 2002 Dr. Blanchard returned to Australia to join the Institute for Glycomics at Griffith University, setting up a research group in structural biology as well as establishing X-ray crystallography within the Institute. Currently her team comprise three Ph. D students, two international internship project students and two visiting students. Her research interests are focused on molecular structure and in elucidating interactions between proteins and small molecule ligands, subsequently utilising this information to aide our understanding of how proteins function as well as directing this information into design of inhibitors as potential leads for drugs targeting proteins with roles in disease. Her research includes the determination of protein atomic structure by X-ray crystallography, the analysis of molecular interactions by crystallography and by NMR, molecular modelling and structure analysis and application to structure based drug design. Her recent focus is in glycoscience, and in particular how carbohydrate-recognising proteins (lectins) are able to recognise oligosaccharides on host-cells and use such interactions during infection processes. One major area that she is developing is that of virus recognition of host-cells and another major research program is focused on galectins that are involved in cancer progression. Ultimately the design of inhibitors of these pathogens and proteins could reduce their ability to progress disease.
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Rotavirus and Sialic Acid Recognition
Helen Blanchard (Institute for Glycomics, Griffith University)
in collaboration with Barbara Coulson# and Mark von Itzstein*
*Institute for Glycomics, Griffith University
#Department of Microbiology and Immunology, The University of Melbourne.
Rotavirus infection results in high incidence of gastroenteritis in the young, leading to death of approximately 600,000 children annually, worldwide. Rotaviruses only infect mature enterocytes on intestinal villi suggesting existence of a specific host cell-receptor, however attachment of the virion is a complex process with multiple cell surface interactions, some being species-specific. Rotavirus cell attachment has been generally considered to be dependent (“sialidase-sensitive”) or independent (“sialidase-insensitive”) of the presence of sialic acid in cell surface glycoconjugates such as gangliosides. However, the exact nature of the critical chemical components is undefined, and involvement of sialic acid is controversial. Host-cell attachment occurs via the outer capsid spike protein that contains a carbohydrate-binding domain VP8*, critical in the recognition of cell-surface glycoconjugates. We are investigating rotavirus host-cell recognition and attachment, particularly in relation to carbohydrate-binding properties of VP8*, ultimately directing this information into design of potential drugs. We have determined crystal structures of VP8* of strains CRW-8, RRV and Wa that infect pigs, monkey and humans respectively. Our preliminary reports described the first crystallographic information on VP8* from a strain that infects humans, and that appears to demonstrate sialic-acid independent infection. These structures of VP8* from strains considered to be sialic-acid dependent (CRW-8) and independent (Wa) [1] as well as our crystal structures of Rhesus Rotavirus (RRV) wild-type and an Arg101Ala mutant have enabled us to investigate aspects of proposed sialic-acid dependency [2]. This work along with our STD-NMR and infectivity inhibition studies to assess the binding and effect of ligands on infectivity, has enabled us to counter the widely-accepted paradigm that sialic acids are irrelevant in host cell recognition by sialidase-insensitive rotaviruses.
References
[1] H. Blanchard, X.Yu, B.S. Coulson, M. von Itzstein Journal of Molecular Biology Volume 367, Issue 4, Pages 1215-1226, (2007)
[2] M.J. Kraschnefski; A. Bugarcic; F. E. Fleming; X. Yu; M. von Itzstein; B.S. Coulson; H. Blanchard Glycobiology 19(3):194-200, (2009)
[3] T. Haselhorst, F.E. Fleming, J.C. Dyason, R.D. Hartnell, X.Yu, G. Holloway, K. Santegoets, M.J. Kiefel, H. Blanchard, B.S. Coulson, M. von Itzstein. Nat. Chem. Biol. Feb; 5(2):91-93, (2009)
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