Pregnancy Research
See full list of projects
Investigating matrix metalloproteinases and their inhibitors as biomarkers of preterm labour - also offered as MBiomedSc
Supervisors: Dr Harry Georgiou
Project Site: Mercy Hospital for Women and/or Royal Women’s Hospital
Contact: Dr Harry Georgiou; E: harrymg@unimelb.edu.au T:8345 3708
Project description: Currently, there are no biomarkers that can accurately predict if and when preterm labour will occur. This study will investigate MMPs and TIMPs in the vaginal fluid of women with symptoms of preterm labour (‘threatened preterm labour’) and to correlate this with cervical and fetal fibronectin status.
Stem cells and their Potential to Treat Clinically Important Disorders of Pregnancy - also offered as MBiomedSc
Supervisors: Dr Bill Kalionis
Project Site: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Bill Kalionis T: 8345 3748 E: bill.kalionis@thewomens.org.au
Project Description: We are interested in the potential for manipulating gene expression in decidual mesenchymal stem cells as for the treatment for clinically important pregnancy disorders such as preeclampsia.
The latter stages of preeclampsia are characterised by an environment of high oxidative stress in the decidua. We have shown that decidual MSCs are abnormal in their response to oxidative stress in preeclampsia. The aim of the project is to use human cell culture models to test strategies for restoring normal oxidative stress response to abnormal, preeclampsia-affected decidual MSCs (PE-DMSCs). For example, we have shown that aldehyde dehydrogenase expression, which is required for MSCs to resist oxidative stress, is abnormally low in PE-DMSCs. We will increase expression of aldehyde dehydrogenase in PE-DMSCs using plasmid-based expression vectors and test whether resistance to oxidative stress in PE-DMSCs is restored.
Techniques: stem cell preparation and characterisation by immunocytochemistry and FACS, RNA/DNA extraction methods, real-time PCR, siRNA and gene overexpression analysis and immunohistochemistry. Functional analyses will include proliferation, migration and differentiation assays.
Stem Cell Microvesicle Repair of the Damaged Endothelium in Preeclampsia - also offered as MBiomedSc
Supervisors: Dr Bill Kalionis
Project Site: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Bill Kalionis T: 8345 3748 E: bill.kalionis@thewomens.org.au
Project Description: Preeclampsia is the most significant clinical disorder of pregnancy, affecting 5% of all pregnancies. Preeclampsia is a significant cause of maternal morbidity as well as fetal morbidity and mortality. Currently, there are no early diagnostic tests or effective treatments for preeclampsia. We are interested in the potential for subcellular microvesicles shed from mesenchymal stem cells to treat the symptoms of preeclampsia.
In preeclampsia, the endothelial cells lining the vessel walls become damaged. Systemic vascular damage contributes significantly to the symptoms of preeclampsia. Microvesicles shed from stem cells contain a variety of beneficial growth factors, cytokines and microRNAs that can be delivered to damaged cells, which prevent cell apoptosis, promote cell proliferation and differentiation, and thereby assist cells in recovering from damage. The aim of the project is to identify the growth factors, cytokines and microRNAs produced by microvesicles derived from placental mesenchymal stem cells.
Techniques: Stem cell preparation and characterisation by immunocytochemistry, flow cytometry and differentiation assays, microvesicle preparation from stem cells, ultracentrifugation, microvesicle characterisation and fluorescence labelling, screening assays for microRNA, growth factors and cytokines.
How do hormones work: investigating new steroid receptors
Supervisors: Dr. Penelope Sheehan
Project Site: Pregnancy Research Centre, Royal Women’s Hospital
Contact: Dr Penelope Sheehan E: penny.sheehan@thewomens.org.au
Project Description: Progesterone is known to be a key hormone in human pregnancy and is particularly thought to play a role in maintaining myometrial quiescence throughout gestation, allowing the fetus to grow. Antiprogestins, such as mifepristone (RU 486), are known to contribute to parturition1. Yet, in humans, maternal serum progesterone concentrations do not significantly decrease at labour onset2, suggesting a change at the receptor level. However detailed knowledge of intracellular and molecular mechanisms are unknown. We have identified two new receptors capable of binding progesterone which may help improve our understanding of progesterone action. The pregnane X receptor (PXR) is a nuclear receptor which is able to regulate gene transcription. The endogenous ligand with the highest affinity for the PXR is the progesterone metabolite, 5βDHP. Progesterone receptor membrane components 1 and 2 (PGRMC1, PGRMC2) are also putative progesterone receptors. Detailed study of the pathways affected by these receptors using myometrial explant cultures and gene silencing techniques may provide new therapeutic targets for treatment of preterm birth and also for induction of labour in postdates pregnancy.
This project will build on previous Pregnancy Research Centre findings identifying changes in expression of these two new receptors in association with human labour at term in myometrium. The methodologies are established within our laboratories at The Royal Women’s Hospital.
Techniques: Tissue culture, siRNA gene silencing, Real-time RT-PCR, western immunoblotting, microarray.
Day 11 explant with myometrial cells growing into the culture medium ready for experiment
Can dietary phytophenols prevent the development of diabetes in pregnancy? - also offered as MBiomedSc
Supervisors: Associate Professor Martha Lappas
Project site: Department of Obstetrics & Gynaecology, University of Melbourne located at the Mercy Hospital for Women
Contact: T: 8458 4370 E: mlappas@unimelb.edu.au
Project description: Gestational diabetes mellitus (GDM) affects up to 20% of all pregnancies. It has an impact that extends well beyond pregnancy and childbirth, with the potential for lifelong morbidity or mortality for both mother and baby. Despite the enormous health-impact of this condition, little progress has been made with interventions aimed at prevention; rates of GDM are increasing in parallel with the obesity epidemic. A safe and effective intervention that can reduce the burden of GDM would be a major public health initiative. Of promise, however, is the increasing volume and quality of evidence that high fruit and vegetable intake in pregnancy is associated with a decreased risk of adverse pregnancy outcomes. Many of the beneficial effects are due to phytophenols which are natural products found in fruits and vegetables and beverages derived from plants. Thus, in this study, we will use a mouse model to determine if phytophenols can prevent the development of GDM.
Techniques: Animal work, PCR-based analysis, Western blotting and ELISA
Can dietary phytophenols stop preterm birth? - also offered as MBiomedSc
Supervisors: Associate Professor Martha Lappas
Project site: Department of Obstetrics & Gynaecology, University of Melbourne located at the Mercy Hospital for Women
Contact: T: 8458 4370 E: mlappas@unimelb.edu.au
Project description: The single most important complication contributing to poor pregnancy and neonatal outcome is preterm birth. Of the 130 million babies born each year, 8 million die before their first birthday. Up to 2.7 million of these deaths are attributable to being born too early. Bacterial infection is the most common trigger for preterm birth. It activates inflammation in placenta which can trigger the processes that lead to preterm birth. In our in vitro studies, we have shown that natural plants chemicals (i.e. phytophenols), such as luteolin which is found in celery, can reduce inflammation in the placenta. Although this data is very promising, in vivo studies are needed to determine if these plant chemicals will be useful as therapeutics to prevent preterm birth. In this project, we will induce preterm birth in mice (using bacterial infection). We will then determine if phytochemicals can prevent infection induced preterm birth. The possibility of phytophenols as therapeutic agents offers an exciting step forward into the management of a condition responsible for unequalled morbidity and mortality in infants.
Techniques: Animal work, PCR-based analysis, Western blotting and ELISA
Testing novel therapeutics in a novel mouse model of preeclampsia - also offered as MBiomedSc
Supervisors: Dr Natalie Hannan and Prof Stephen Tong
Project Site: Mercy Hospital for Women, Heidelberg (Dept. Obstetrics and Gynaecology)
Contact: Dr Natalie Hannan E: nhannan@unimelb.edu.au
Project description: Preeclampsia affects around 2-8% of all pregnancies, and claims the lives of over 60,000 women annually with far greater rates of perinatal loss. There is no medical therapeutic available, besides the delivery of the placenta and baby. A treatment is urgently needed. This project will use an innovative mouse model of preeclampsia to test novel therapeutic strategies to prevent, delay or treat preeclampsia. This model is unique in that it overexpresses the toxins of preeclampsia specifically in the placenta (via lentiviral transduction of mouse blastocysts) similar to the disease in women.
Understanding the pathophysiology of preeclampsia - also offered as MBiomedSc
Supervisors: Dr Natalie Hannan and Prof Stephen Tong
Project Site: Mercy Hospital for Women, Heidelberg (Dept. Obstetrics and Gynaecology)
Contact: Dr Natalie Hannan E: nhannan@unimelb.edu.au
Project description: Preeclampsia affects around 2-8% of all pregnancies, and claims the lives of over 60,000 women annually with far greater rates of perinatal loss. There are no efficacious treatments available or predictive tests for early diagnosis. This project aims to understand the pathophysiology behind this disease by examining key pathways thought to be central to disease progression and severity in clinical samples and animal models of disease.
Understanding changes in haemostasis during pregnancy and pregnancy complications - also offered as MBiomedSc
Supervisors: A/Prof Joanne Said and Dr Briony Cutts
Project Site: Melbourne Medical School, Sunshine Hospital, St Albans.
Contact: E: jsaid@unimelb.edu.au or briony.cutts@thewomens.org.au
Project description: Haemostasis in humans represents a complex balance between prothrombotic and anticoagulant proteins. During pregnancy, this balance is shifted in favour of a prothrombotic state such that pregnant women have an increased risk of developing deep vein thrombosis. This disturbance in coagulation is even more pronounced in a range of pregnancy complications. The aim of this study is to investigate the changes that occur during pregnancy, and in various adverse pregnancy conditions, using the calibrated automated thrombinoscope. This modern technology allows a global assessment of haemostasis rather than investigating individual factors. The project will be conducted in the brand new laboratories at the Centre for Health Research and Education based at Sunshine Hospital. Sunshine Hospital is the second largest maternity unit in Victoria and thus there is an ample population of pregnant women available to participate in this study. Techniques: Recruitment of patients, sample collection, thrombin generation assays.