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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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Jeremy Turnbull, PH.D.
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)
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| Dr. Turnbull's Research |
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National Library of Medicine, Directory of Health Organizations (SIS) website, as well as the link for Patient
Information on The Diseases Database a cross-referenced index of human disease, and the Intute: health & life
sciences a free online service providing access to the very best Web resources for education and research
located in the UK
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