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PROJECT: (Basic) Stem Cells of Ovarian Follicles. R. O&G. Supervisors Professor Ray Rodgers Project Background Our laboratory has shown that a proportion of granulosa cells isolated directly from antral follicles have a number of stem cell properties. These include the ability to divide under anchorage independent conditions [2], divide without contact inhibition [1] and express telomerase [3]. On this basis we proposed the model shown in the above figure [1]. It assumes plutipotentiality into at least cumulus cells (specialized cells surrounding the oocyte) and mural granulosa cells. The pluripotency of granulosa stem cells has yet to be demonstrated, however in mice expressing a dominant-stable mutant of betacatenin, clonally derived granulosa cell tumours develop. These can be of granulosa, bone or neural phenotype [4], suggesting that tumours of granulosa cells are pluripoten. The goals of this project are to investigate the pluripotential of granulosa cells. PROJECT: (Basic) Thecal stem cells – Real or not? R. O&G. Supervisors Professor Ray Rodgers Project Background In a recent Proceedings of the National Academy of Sciences article, ‘thecal stem cells’ [5] were reported in new born mice. However in this species follicles are still developing at birth. Whole ovaries were treated with collagenase and from this a heterogeneous mixture of cells was cultured and colonies of stem cells were identified in anchorage-independent culture. The authors identified expression of markers found in thecal cells, which in vivo are only expressed in the presence of granulosa cells. However they did not examine the colonies to see if all cells expressed the markers. Therefore it is possible that the colonies were of mixed cell type, containing granulosa stem cells and some thecal cells. Certainly the colonies bore a sticking resemblance to granulosa stem cells [2]. References Rodgers RJ, Lavranos TC, van Wezel IL, Irving-Rodgers HF. Development of the ovarian follicular epithelium. Mol Cell Endocrinol 1999; 151: 171-179. Lavranos TC, Rodgers HF, Bertoncello I, Rodgers RJ. Anchorage-independent culture of bovine granulosa cells: the effects of basic fibroblast growth factor and dibutyryl cAMP on cell division and differentiation. Exp Cell Res 1994; 211: 245-251. Lavranos TC, Mathis JM, Latham SE, Kalionis B, Shay JW, Rodgers RJ. Evidence for ovarian granulosa stem cells: telomerase activity and localization of the telomerase ribonucleic acid component in bovine ovarian follicles. Biol Reprod 1999; 61: 358-366. Boerboom D, White LD, Dalle S, Courty J, Richards JS. Dominant-stable beta-catenin expression causes cell fate alterations and Wnt signaling antagonist expression in a murine granulosa cell tumor model. Cancer Res 2006; 66: 1964-1973. Honda A, Hirose M, Hara K, Matoba S, Inoue K, Miki H, Hiura H, Kanatsu-Shinohara M, Kanai Y, Kono T, Shinohara T, Ogura A. Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells. Proc Natl Acad Sci U S A 2007; 104: 12389- 12394. PROJECT: (Basic) Bioinformatics of Ovarian Follicle Development. R. O&G. Supervisor Professor Ray Rodgers Bioinformatics is a newly emerging area of increasing importance in all areas of biology. Currently there are insufficient numbers of bioinformaticians to satisfy the need to fully exploit the explosion of data currently available, much less that to be produced in the future. Microarrays produce a wealth of data. We have conducted over 70 Affymetrix gene expression arrays each with over 20,000 probe sets which equates over 1.5 million pieces of data from our experiments alone. We have arrays performed on RNA isolated different ovarian compartments (theca layers, granulosa cells, cumulus-oocyte complexes) from follicles at different stages of health and development, and from cells (theca and granulosa) in culture. There are numerous computer programs for basic analyses and we routinely use Partek and Ingenuity Pathway Analysis (IPA) and are currently conducting basic analysis of these arrays. We have made novel discoveries of follicle development, not hitherto apparent by previous hypothesis-driven research. Heat Map of gene expression comparing 14 follicles. 21 |
This project will mine our data in greater detail for relationships between in vitro and in vivo data. It will compare our data with other data sets available publicly or collaboratively from ovaries of other species, from other organs and cell types and diseases identified by IPA. It will identify unique novel markers of cell types and behaviours in follicles. Key words Bioinformatics, microarray, computer analyses. PROJECT: (Basic) Ovarian fetal stroma and PCOS (polycystic ovary syndrome). R. O&G. Supervisors Professor Ray Rodgers Katja Hummitzsch Project Background Polycystic ovary syndrome (PCOS) is the commonest endocrine condition affecting an estimated 5-7% of women of reproductive age in Western societies, and is a major burden on health costs. It is characterised by hyperandrogenaemia and hirsutism, chronic anovulation, and polycystic ovaries. Affected women are also at increased risk of anovulatory infertility, obesity, hyperlipidaemia, type II diabetes and possibly cardiovascular disease. Its causes are not well understood but it is thought that there is both a genetic predisposition and a fetal cause. The ovary also has excessive collagen and stroma, which in other tissues, is due to increased activity of transforming growth factor-β. In a recent study (1) we found that fibrillin 3, thought to regulate TGFβ activity in tissues and a gene that is familiarly linked to PCOS is expressed in fetal ovaries at a critical time when follicles are forming and the ovarian stroma is expanding. This project will examine cultured bovine fetal ovarian cells to determine which cells express fibrillin 3 and to examine how fibrillin 3 is regulated during gestation. This information is the critical next step in understanding the causes of PCOS, and hopefully its prevention. The project will involve primary cell culture from ovaries obtained from an abattoir and basic cell and molecular biology techniques. Reference Hatzirodos N, Bayne RA, Irving-Rodgers HF, Hummitzsch K, Sabatier L, Lee S, Bonner W, Gibson MA, Rainey WR, Carr BR, Mason HD, Reinhardt DP, Anderson RA, Rodgers RJ (2011) Linkage of regulators of TGFβ activity in the fetal ovary to polycystic ovary syndrome. FASEB Journal 25, 2256-2265. 22 |
Page 1: 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 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 54 and 55: Craniofacial Research Group Contact
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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