Application for Promotion to Associate Professorship
Dr. Angela Savage
Research Activities
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 β-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.
In 2005, I was one of five Irish scientists (two in Galway, three at Dublin City University)
funded under an initiative from the Industrial Development Authority in conjunction with BristolMyers Squibb. The total grant is in the region of €10 million.
The main themes of my 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.
Research Achievements
•
48 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
2005
Bristol-Myers
Squibb / Industrial
Develop. Authority
~€2,000,000 Rapid on-line analysis of glycoprotein therapeutics
3