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

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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. 53 |
Techniques that will be used in the projects include human cell culture, animal studies, micro-computed tomography, gene transfection, real-time RT-PCR, luciferase assay, mineralization assay, proliferation assay, western blot, immunohistochemistry and confocal microscopy. References Anderson PJ, DJ Netherway, P Self and DJ David. Scanning electron microscope and Micro CT evaluation of cranial sutures in health and disease. Journal of Craniofacial Surgery 17, 909-919, 2006. Coussens AK, CR Wilkinson, IP Hughes, CP Morris, A van Daal, PJ Anderson and BC Powell. 2007. Unravelling the molecular control of calvarial suture morphogenesis in children with craniosynostosis. BMC Genomics. 8:doi: 10.1186/1471-2164-8-458. Coussens AK, CR Wilkinson, IP Hughes, BC Powell, PJ Anderson and A van Daal. 2008. Identification of genes differentially expressed by prematurely fused human sutures using a novel in vivo-in vitro approach. Differentiation. 76:531-545. Donato R, SA Wood, I Saunders, B Gundsambuu, KY Mak, CA Abbott and BC Powell. 2009. Regulation of epithelial apical junctions and barrier function by Galpha13, Biochim Biophys Acta - Molecular Cell Research 1793, 1228-1235. These projects are eligible for the WCHRI Honours Scholarship of $2,000. See the website for further details and how to apply http://www.wchri.com.au/Scholarships.htm. 54 |
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SCHOOL OF PAEDIATRICS AND REPRODUCT
Page 4 and 5: Make a difference "The recent Excel
Page 6 and 7: Honours graduate career pathways Ou
Page 8 and 9: Honours Scholarships and Support Sc
Page 10 and 11: Discipline of Obstetrics and Gynaec
Page 12 and 13: Discipline of Obstetrics and Gynaec
Page 14 and 15: Clinical Studies and Trials The Obe
Page 16 and 17: Cerebral Palsy Research Group The C
Page 18 and 19: products, but also naturally occurr
Page 20 and 21: disruption of either Clock or Bmal1
Page 22 and 23: PROJECT: (Basic) Stem Cells of Ovar
Page 24 and 25: Early Development Group Contact Per
Page 26 and 27: Early Life Programming of Health an
Page 28 and 29: persist long term. There is new evi
Page 30 and 31: PROJECT: (Basic) Behavioural effect
Page 32 and 33: Gamete and Embryo Biology Laborator
Page 34 and 35: improve developmental potential in
Page 36 and 37: PROJECT: (Basic) Factors that regul
Page 38 and 39: Pregnancy and Development Group Con
Page 40 and 41: Reproductive Biotechnology Group Su
Page 42 and 43: that versican is pivotal in promoti
Page 44 and 45: Reproductive Endocrinology Group Su
Page 46 and 47: Treg fate-determining transcription
Page 48 and 49: PROJECT: (Basic) Viral Recognition
Page 50 and 51: Child Nutrition Research Centre (CN
Page 52 and 53: PROJECT: (Basic) Measurement of vit
Page 56 and 57: Lysosomal Biology, Lysosomal Diseas
Page 58 and 59: Matrix Biology Unit Location: Women
Page 60 and 61: Molecular Immunology Cheryl Brown P
Page 62 and 63: Fig 4. Lentiviral delivery of shRNA
Page 64 and 65: the two most common human polyA exp
Page 66 and 67: Paediatrics and Child Health, Flind
Page 68 and 69: Vaccine Safety Research Group Super
Page 70 and 71: introduction of the rotavirus vacci
Page 72: Index Breast Biology and Cancer, 16
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