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Structure and Biosynthesis of Mouse Brain Heparan Sulphate
Abstract 2005 MHE Conference
Jeremy Turnbull, Katherine Drummond, Alex Holme & Scott Guimond,
School of Biological Sciences, University of Liverpool,
Crown Street, Liverpool, L69 7ZB. England, UK.
Heparan sulfate (HS) biosynthesis involves the action of a complex set of enzymes with polymerase (EXT), epimerase and
sulfotransferase (ST) activities. Multiple isoforms of N- and O-STs decorate the nascent HS chains with specific sulfation
patterns which confer selective biological functions.
We have been studying HS structure and biosynthesis in model organisms such as mice and nematode worms since they
provide opportunities to study the expression of these enzymes in relation to the structure and activities of the HS produced.
In previous studies in mice we found that there are stage-specific combinations and distinct spatiotemporal expression patterns
of HSST isozymes that underlie the synthesis of different HS species in developing brain.
This data indicated that differential HS biosynthesis results in the synthesis of structurally variant HS species which form
functional signaling complexes with growth factors essential for normal brain development.
Regulated synthesis and the levels of specific HS species could be a mechanism for regulation of proliferation and differentiation
in the developing brain. In recent studies we have become interested in the possibility that the levels or structures of HS may be
altered in the brain tissues of mice heterozygous for the EXT1 gene, and that biochemical defects of this type could underly
nervous system abnormalities observed in humans with this genotype.
We have purified HS from normal and EXT1 +/- mice and are currently performing detailed structural analyses on these
samples. Data will be presented to address the question as to whether there are alterations in the amounts and/or structures
of HS produced in the brains of EXT1 +/- mice.
Abstract 2005 MHE Conference
Jeremy Turnbull, Katherine Drummond, Alex Holme & Scott Guimond,
School of Biological Sciences, University of Liverpool,
Crown Street, Liverpool, L69 7ZB. England, UK.
Heparan sulfate (HS) biosynthesis involves the action of a complex set of enzymes with polymerase (EXT), epimerase and
sulfotransferase (ST) activities. Multiple isoforms of N- and O-STs decorate the nascent HS chains with specific sulfation
patterns which confer selective biological functions.
We have been studying HS structure and biosynthesis in model organisms such as mice and nematode worms since they
provide opportunities to study the expression of these enzymes in relation to the structure and activities of the HS produced.
In previous studies in mice we found that there are stage-specific combinations and distinct spatiotemporal expression patterns
of HSST isozymes that underlie the synthesis of different HS species in developing brain.
This data indicated that differential HS biosynthesis results in the synthesis of structurally variant HS species which form
functional signaling complexes with growth factors essential for normal brain development.
Regulated synthesis and the levels of specific HS species could be a mechanism for regulation of proliferation and differentiation
in the developing brain. In recent studies we have become interested in the possibility that the levels or structures of HS may be
altered in the brain tissues of mice heterozygous for the EXT1 gene, and that biochemical defects of this type could underly
nervous system abnormalities observed in humans with this genotype.
We have purified HS from normal and EXT1 +/- mice and are currently performing detailed structural analyses on these
samples. Data will be presented to address the question as to whether there are alterations in the amounts and/or structures
of HS produced in the brains of EXT1 +/- mice.
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Research authored by Dr. Turnbull
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List of Publications via PubMed
(NIH National Library of Medicine)
List of Publications via PubMed
(NIH National Library of Medicine)
| Jeremy Turnbull, Ph.D., research |
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2009 Conference abstract
Elucidating the Functions of Heparan Sulfates: Towards Glycomics Strategies
J Turnbull, Y Ahmed, A Atrih, AK Powell, T Puvirajesinghe, R Miller, M Skidmore,
EA Yates and S Guimond.
Centre for Glycobiology, School of Biological Sciences, University of Liverpool, Liverpool, L69 7ZB, UK.
e-mail: j.turnbull@liverpool.ac.uk
The structural diversity of heparan sulphates (HS) remains an enigmatic molecular puzzle, and the potential role of specific
sequences is a complex and controversial issue. To address the central question of the extent of biological specificity of HS
sequences, we have established a number of new experimental strategies aimed at developing glycomics strategies for studying
HS. These include:
• Rapid isolation and purification of HS from tissues;
• Improved tags for high sensitivity disaccharide composition analysis using fluorescence detection;
• Generation of oligosaccharide libraries which can be exploited for binding studies and bioassay screening;
• Array methodologies for high throughput analyses including glycoarrays for probing binding specificities and
"glycobioarrays" for screening biological responses;
• Improved methods for separation of HS oligosaccharides;
• Accurate sequencing methods using electrospray-mass spectrometry.
The application of these methods has yielded a variety of data that provide novel insights into the biological selectivity of HS
structures, and demonstrate that chemical information encoded in the complex sulfation sequences of HS chains conveys
functional specificity. Further application and extension of these strategies will permit development of glycomics scale
approaches to decode the molecular basis of HS function in specific biological contexts.
Elucidating the Functions of Heparan Sulfates: Towards Glycomics Strategies
J Turnbull, Y Ahmed, A Atrih, AK Powell, T Puvirajesinghe, R Miller, M Skidmore,
EA Yates and S Guimond.
Centre for Glycobiology, School of Biological Sciences, University of Liverpool, Liverpool, L69 7ZB, UK.
e-mail: j.turnbull@liverpool.ac.uk
The structural diversity of heparan sulphates (HS) remains an enigmatic molecular puzzle, and the potential role of specific
sequences is a complex and controversial issue. To address the central question of the extent of biological specificity of HS
sequences, we have established a number of new experimental strategies aimed at developing glycomics strategies for studying
HS. These include:
• Rapid isolation and purification of HS from tissues;
• Improved tags for high sensitivity disaccharide composition analysis using fluorescence detection;
• Generation of oligosaccharide libraries which can be exploited for binding studies and bioassay screening;
• Array methodologies for high throughput analyses including glycoarrays for probing binding specificities and
"glycobioarrays" for screening biological responses;
• Improved methods for separation of HS oligosaccharides;
• Accurate sequencing methods using electrospray-mass spectrometry.
The application of these methods has yielded a variety of data that provide novel insights into the biological selectivity of HS
structures, and demonstrate that chemical information encoded in the complex sulfation sequences of HS chains conveys
functional specificity. Further application and extension of these strategies will permit development of glycomics scale
approaches to decode the molecular basis of HS function in specific biological contexts.
| Photo's taken during the Third International MHE Research Conference |
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