Application for Promotion to Associate Professorship
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Research For more than 20 years in Galway, my research has been in the area of Carbohydrate Chemistry, more specifically the isolation and structure determination of oligosaccharides from glycoproteins and of polysaccharides from bacteria and plants. My PhD thesis concerned the structure determination of bacterial polysaccharides (Prof. GGS Dutton, UBC, Vancouver) while my postdoctoral work was on diseases of mucopolysaccharide degradation (Children’s Hosptial, Vancouver) and on the cell surface glycoprotein of African Trypanosomes (Giessen, Germany). Following my appointment as Junior Lecturer in 1983, I started work on the isolation and structure determination of O-linked mucins derived from bovine submaxillary mucin. I perused veterinary textbooks, helped a veterinary inspector at the local abattoir to remove the submaxillary glands from about 20 cows, and then carried out the extraction of submaxillary mucin without any technical help. The oligosaccharides were released from the mucin by -elimation and then separated by high pressure liquid chromatography. The structures were then determined by nuclear magnetic resonance spectroscopy at 270MHz. This work resulted in the characterization of a range of novel neutral and sialylated oligosaccharides, some with blood group activity. I spent the summer of 1984 working on the oligosaccharide structures of porcine submaxillary mucin at the Vrije Universiteit in Amsterdam where in 1988 I spent a six-month sabbatical period investigating the high mannose oligosaccharides from human chorionic gonadotrophin. Following the receipt of funding from the EU and Forbairt in 1993 and the purchase of a Dionex chromatography system, I extended my research into the area of N-linked oligosaccharides from recombinant glycoproteins. I collaborated with scientists in Braunschweig, Germany in using MALDI–TOF mass spectrometry to characterise the oligosaccharide structures of a recombinant fusion glycoprotein expressed in mammalian cell culture. In 1996 I obtained funding from the Wellcome Trust for the purchase of a 400MHz NMR instrument. This allowed me re-entry into the field of structure determination of bacterial polysaccharides. I initiated a very fruitful collaboration with Prof. Alexander Shashkov from Moscow who visited my laboratory each year for six years for 6-8 week visits. In addition, PhD students made six visits to Moscow, funded by Enterprise Ireland. This collaboration also included Dr. Anthony Moran, Microbiology Department, NUI Galway. I have also done a considerable amount of work with Dr. Maria Tuohy, Biochemistry Department, on the separation of plant derived oligosaccharides using Dionex chromatography along with the use of NMR spectroscopy for structural analysis of novel oligosaccharides and determination of the stereochemical mode of action of polysaccharide-degrading enzymes. Other local collaborations in the use of Dionex chromatography have included colleagues in Botany (Prof. Guiry, and Dr. Micheline Sheehy-Skeffington), Zoology (the late Prof. Keegan) and Physics (Prof. G. Jennings). My group has also worked on Coeliac Disease with Prof. Ciaran McCarthy and Dr. Fiona Stevens, Department of Medicine, University College Hospital Galway. In 2002 I spent a month as a visiting scientist at the Chemistry Department of Wuhan University. I gave a number of seminars to PhD students and staff to introduce the use of 600 MHz NMR spectroscopy for structure determination of polysaccharides of traditional Chinese medicines. To complete NMR training, a PhD student visited my laboratory for two months. I also gave considerable help to the members of the Chemistry and other departments with the writing and editing of manuscripts. Application for Promotion to Associate Professorship Dr. Angela Savage I have obtained a number of grants from BioResearch Ireland’s Galway research center, the National Diagnostics Centre, and I have also obtained joint funding from both Enterprise Ireland and the Higher Education Authority under PRTLI with its Director, Dr. Terry Smith, for research on the glycosylation analysis of recombinant glycoproteins. Following the appointment of Dr. (now Prof.) Smith to the position of Director of the National Centre for Biomedical Engineering Science in Galway, I have been involved as lead scientist with him and with scientists at Dublin City University in an application to Science Foundation Ireland for a multimillion euro research grant in association with a major biopharmaceutical company located in Ireland to set up a Glycobiology research centre in Galway. The main themes of the research project are: (i) The rapid, real-time analysis of the structures of the complex oligosaccharides of recombinant biopharmaceutical products, with a view to optimizing yield and (ii) The potential of genetically engineered plant cell lines for expression of recombinant biopharmaceutical products. Such a Glycobiology research centre in Galway would be an excellent adjunct to the IDA’s €80 million technology centre to be located in the midlands to serve as a research resource for the biopharmaceutical companies located in Ireland (e.g. Wyeth and Bristol-Myers-Squibb) and for the many such companies which the IDA is currently in the process of attracting to Ireland. Research Achievements 45 publications in peer-reviewed journals 1 book chapter, and 1 review in Carbohydrate Research 26 oral presentations at major conferences 30 additional invited lectures 52 poster presentations at major conferences 8 presentations and Convenor on Glycoscience Conferences on World Wide Web. Chaired many sessions at major conferences, mostly abroad 3 book reviews Guest Editor, special issue of Carbohydrate Polymers, 1991 Co-editor, Abstract book, 10th European Carbohydrate Symposium, 1999 Member, Editorial Board, Carbohydrate Research 2000- Referee: Carbohydrate Research, Glycoconjugate J., Eur. J. Biochemistry, RSC Supervised 9 PhD students. Contributed to supervision of 12 others. Successful grant applications: EU, Wellcome Trust, Enterprise Ireland, Forbairt, Health Research Board, BioResearch Ireland, President’s Travel Fund Organised three major conferences on Carbohydrates (see below) 2 Application for Promotion to Associate Professorship Dr. Angela Savage Research Funding Year Funding Agency Amount Project 1985 U.C.G. £ 1,500 Gel Permeation Chromatography Equipment 1986 Alexander von Humboldt Found’n. £ 1,000 Kugelrohr Separation Equipment 1993 EU BRIDGE £90,000 Glycosylation Analysis of Glycoprotein Therapeutics 1993 Forbairt £15,000 Towards purchase of Dionex chromatography system 1995 Wellcome Trust £85,000 Toward purchase of 400 MHz NMR 1995 Health RB £18,000 Toward purchase of 400 MHz NMR (VAT) 1995 BioResearch Ireland £ 3,000 Glycosylation Analysis of Glycoprotein Therapeutics 1997 Pfizer Inc (USA) Confidential With Prof. RN Butler and Prof. PA McArdle, Toward purchase of 400 MHz NMR 1997 Forbairt Strategic Research £66,000 With Dr. Terry Smith: Production of therapeutic proteins in animal cell culture 1997 Forbairt Basic Research £49,000 With Dr. Maria Tuohy: Structural characterization of galactomannan polysaccharides and their enzymatic hydrolysis products. 1997 Forbairt Int Collaboration £ 3,600 Visits of PhD students to Moscow 1999 BioResearch Ireland £ 4,000 Glycosylation Analysis of Glycoprotein Therapeutics 1999 Enterprise Ireland Int Collaboration £ 4,000 Visits of PhD students to Moscow 1999 HEA PRTLI I £51,000 With Prof. Terry Smith: Development of recombinant glycoprotein systems in cultured CHO cells 2001 Enterprise Ireland Int Collaboration £ 4,500 Visits of PhD students to Moscow Total £ £395,600 Total € > €500K 3
