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

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PROJECT: (Basic) Factors that regulate placental trophoblast invasion and angiogenesis. R. O&G. Supervisor Professor Claire Roberts Project Background Angiogenesis is an essential feature of placental morphogenesis. We have shown that a number of factors expressed in the placenta promote placental trophoblast differentiation and invasion and some of these may also be involved in angiogenesis which uses common molecules to promote endothelial development. The molecular pathway that we have discovered regulates placental invasion may or may not include a signal transduction pathway from the IGF2 receptor complex. This pathway may also regulate angiogenesis. This project will utilise several human trophoblast and endothelial cell lines to demonstrate the molecular pathways involved in invasion and angiogenesis. The project will involve cell culture, RT-PCR, ELISAs, immuno-histochemistry, video image analyses and western blotting. The student will gain skills in a variety of experimental techniques, as well as data management and statistical analyses. PROJECT: (Basic) Molecular mechanisms in actions of transforming growth factor β1 (TGFβ1) inhibition of trophoblast invasion and induction of terminal differentiation. R. O&G. Supervisor Professor Claire Roberts Project Background Although it is known that TGFβ1 inhibits trophoblast invasion and likely induces terminal differentiation the detailed molecular mechanisms by which this occurs are not understood. Trophoblast invasion is an important process in early pregnancy that is responsible for dramatic re-modelling of the uterine vasculature to permit the 12-fold increase in uterine blood flow that occurs in normal pregnancy. This process is influenced by the low oxygen environment in first trimester placenta. In the second half of pregnancy placentation is characterised by terminal differentiation of trophoblasts with the development of a large highly attenuated surface area for exchange. This project will explore the molecular mechanisms by which TGFβ1 regulates placental differentiation and will utilise several human trophoblast cell lines and first trimester and term human placental samples to demonstrate the molecular pathways involved. The project will involve cell culture, RT-PCR, ELISAs, immuno-histochemistry, video image analyses and western blotting. The student will gain skills in a variety of experimental techniques, as well as data management and statistical analyses. PROJECT: (Clinical/basic) Associations between genome damage, DNA repair enzyme gene polymorphisms and B vitamin status. R. O&G. Supervisor Professor Claire Roberts Dr Denise Furness Professor Gus Dekker Project Background We have recently shown that genome damage in circulating lymphocytes in mid pregnancy is more common in women who subsequently develop pregnancy complications in which placental insufficiency is a feature. These include preeclampsia, pre-term birth and intrauterine growth restriction. This project will determine whether genome damage is associated with polymorphisms in genes that encode DNA repair enzymes and whether severity of damage is influenced by B vitamin status and circulating homocysteine. If time permits, tunnel assays to quantify genome damage in sperm of partners of women who develop pregnancy complications will be performed and the results compared with those from men who father normal pregnancies. The student will gain skills in a variety of experimental techniques including cytokinesis block micronucleus cytome assay, PCR and HRM genotyping, as well as data management and statistical analyses. The student will interact with obstetricians and midwives as well as scientists. PROJECT: (Basic) Cytokine gene expression by placental trophoblast cells under hypoxic conditions. R. O&G. Supervisors Professor Claire Roberts Dr Amanda Highet Project Backgound Trophoblast cells form the outer layer of a blastocyst, and provide nutrients to the embryo and develop the epithelial part of the placenta. They are formed during the first stage of pregnancy in a low oxygen environment where they invade into the maternal decidua and spiral arteries, proliferate, differentiate and secrete cytokines. In preeclampsia the trophoblast cells fail to adequately invade as required to promote materno-placental blood flow. The placenta has a local renin-angiotensin system from which angiotensin-II and its degradation product angiotensin-IV are produced. Angiotensins-II and -IV both stimulate the expression of nuclear factor-kappaB, a transcription factor which regulates gene expression of inflammatory cytokines such as 35 |
interleukin (IL)-6 which could modify extracellular matrix composition, stimulate growth factor secretion and promote cell invasion. IL-10 on the other hand is an inhibitor of nuclear factor-kappaB and may be an important regulator of trophoblast inflammatory activity. We have recently shown that polymorphisms in the IL-10 and IL-6 genes known to decrease IL-10 expression and up-regulate IL-6 expression are more frequent in babies (and therefore placentas) from pregnancies complicated by PE. This honours project will use cell culture and real-time PCR gene expression assays to show that 1) trophoblast cells upregulate expression of the IL-6 gene and downregulate IL-10 under low oxygen conditions and that this is further enhanced in the presence of exogenous angiotensin-II and -IV and 2) IL-6 gene expression is increased and IL-10 is decreased in placenta samples from preeclamptic pregnancies compared with normal term placenta. This research aims to acquire new knowledge about trophoblast cell activity in the low oxygen environment by testing our hypothesis that proinflammatory cytokines are up-regulated by angiotensin-II and -IV under low oxygen conditions. Understanding the role of cytokines in hypoxic placenta and how they affect trophoblast activity could provide insight into the pathways that become deregulated in preeclampsia. PROJECT: (Basic) Sex differences in placental gene expression and the X chromosome. R. O&G. Supervisors Prof Claire Roberts Dr Tina Bianco-Miotto Project Background We aim to demonstrate for the first time that X chromosome genes include many that are important in placental development and function and maternal adaptation to pregnancy, and that some of these escape X inactivation and are therefore differentially expressed by the male and female placenta. Most research on this to date has been conducted in mice which emerging evidence shows is unlike the human. Hence we expect our data will challenge established dogma. We expect our research will explain the different patterns of fetal growth observed in males and females before birth. This project will utilise our access to human placental tissues and skill and knowledge base in placental development, fetal growth and epigenetics. This project will involve gene expression analyses of X chromosome genes as well as epigenetic analysis of differentially expressed genes. Other associated projects may be negotiated 36 |
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 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 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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