Honours Project Book - Faculty of Health Sciences - University of ...

Craniofacial Research Group
Contact Person
Associate Professor Barry Powell
Phone: 8161 7652
barry.powell@adelaide.edu.au
Supervisors
Associate Professor Barry Powell
Associate Professor Peter Anderson
Locations: Women’s and Children’s Hospital, Women’s and Children’s Health
Research Institute
Our research involves the study of genes involved in bone growth and craniosynostosis, a developmental disorder
that affects skull growth and mental development in children (Anderson et al., 2006; Coussens et al., 2007; 2008). Our
overarching goal is to understand gene actions in skull growth and to use that knowledge to develop novel
therapeutics to improve treatment of bone disorders in collaboration with clinical colleagues. In the projects
outlined below you will join a team working at the cutting edge of research, using sophisticated molecular and
cellular approaches, cell culture and gene knockout animal models to study gene function. Your research could
impact on the development of adjunctive treatments in the clinical management of craniosynostosis and other
bone growth disorders and provide new insight into the functions of genes and how bone growth is regulated.
PROJECT: (Basic) Application of recombinant proteins
to modify abnormal bone growth.
Project Background
We are studying a genetic craniofacial abnormality
(known as craniosynostosis) that affects skull growth
by causing premature fusion of the skull plates. The
only treatment is transcranial surgery, but where bony
fusion re-occurs surgery is inadequate and novel
therapies are needed. We have discovered that the
proteoglycans, glypican 1 and glypican 3 (GPC1 and
GPC3) regulate activity of the key bone growth
factor, bone morphogenetic protein 2 (BMP2) in
cranial cells.
In this project we will mouse models to test if
manipulation of BMP2 activity can prevent the reoccurrence
of bone growth after surgery. This could
be tested in tissue explants or in vivo. The effects on
bone fusion, BMP2 activity and markers of bone
growth can be assessed.
Outcomes
This research could lead to the development of novel
therapeutic approaches to treat abnormal bone
growth.
PROJECT: (Basic) How do glypicans and bone
morphogenetic proteins interact in cranial bone
growth?
Project Background
The proteoglycans, GPC1 and GPC3, act as coreceptors
for growth factors at the cell surface but
they can also be released extracellulary to bind
them. In this project you will investigate how GPC1
and GPC3 regulate BMP2 in cranial suture cells.
Building on data that GPC1 and GPC3 interact with
BMP2 in vitro, this will be tested in vivo in this project.
We can explore if interaction occurs at the cell
surface or after the proteins have been released from
the cell. The fate of GPC-BMP2 complexes can be
explored. Are they internalised and degraded, or
recycled? Regions responsible for interaction could
be mapped using mutant proteins.
Outcomes
This research will provide insight into how glypicans
and BMPs interact and can therefore have impact in
the broader fields of bone research and
proteoglycan biology.
PROJECT: (Basic) What does retinol binding protein do
in skull growth?
Project Background
Retinol binding protein (RBP) is well known as a
transport protein for retinol in serum and has recently
been implicated in metabolic syndrome. However,
our research shows that it may have other
unexpected functions. We have discovered that RBP
is expressed by skull bone-forming cells and is
dramatically down-regulated in the congenital
condition of craniosynostosis (Coussens et al., 2007)
suggesting that it has a role in skull bone formation.
Our recent data analysing RBP and its receptor
reveal remarkable subcellular locations and
movement within cells.
In this project we aim to determine what RBP and its
receptor do in skull bone-forming cells.
Outcomes
This research will provide insight into the function of
RBP and its receptor in skull bone growth.
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