PhD Scholarship Opportunities

PhD Scholarship Opportunity 1 – Improving treatment stratification for women with early-stage endometrial cancer using Next Gen Sequencing (NGS)

About the Project
Endometrial Cancer (EC) is the 6th most commonly occurring cancer in women globally and is the fifth most diagnosed cancer in Australia in women. The commonest cause of endometrial cancer is genetic (Lynch syndrome), followed by metabolic disturbances such as being overweight, high BMI, high glyceamic load and sedentary lifestyle.  In a recent Australian Longitudinal study young adult women born 1989–95 (“millennials”), demonstrated significant weight gain over time with a BMI expected to exceed 30 (Obese) by age 41 in over 50% of the cohort.  This outcome demonstrates the potential for increased serious health consequences as being obese or overweight is a major risk factor for EC development, even nine years after surgery intervention.    Type 1 endometrial cancers that arise from endometrial hyperplasia, are estrogen driven, account for around 80% of EC and have favorable prognosis. However, they are commonly treated with adjuvant therapy such as radiotherapy which has detrimental impacts on ovarian and uterine functions long term.  Type 1 endometrial cancer consists of four genetically distinct sub-types: POLE ultra-mutated, microsatellite instability hypermutated, copy-number low, and copy-number high with POLE sub-types not requiring any adjuvant therapy – and therefore preserving the reproductive integrity.  Using Next Gen Sequencing (NGS), we can now start to stratify cases into those that require adjuvant therapy and those that don’t.  This project will investigate the development of an NGS screening tool to identify the POLE subtypes from the EC cohorts that we have previously been bio-banked, evaluate the outcomes of these patients overtime with respect to diagnosis and treatments and determine if this NGS tool can be used in cases of hyperplasia to improve our prediction of future EC development.    

Our team has an exciting PhD opportunity for a multidisciplinary NGS project which aims to develop an endometrial cancer and hyperplasia NGS screening tool to improve patient treatment options. The aims of the research are:

1. To develop an NGS screening protocol for POLE mutations using ddPCR.
2. To determine the differential gene expression changes associated with POLE mutations to identify biomarkers of EC progression

To validate these findings in current and future biobanked EC and hyperplasia samples

Supervision
The successful applicant will be supervised by:

• Jacqueline Donoghue, Senior Research Fellow and Project Lead, Gynaecology Research Centre, Department of Obstetrics, Gynaecology and Newborn Health
• Peter Rogers, Deputy Director of the Gynaecology Research Centre, Department of Obstetrics, Gynaecology and Newborn Health and Director of Research at The Royal Women’s Hospital,
• Prof Orla McNally, Director of the Oncology and Dysplasia Service at The Royal Women’s Hospital and the Gynaecological Tumour Stream Lead for the Victorian Comprehensive Cancer.

The student will join the Gynaecology Research Group based at the Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne and will work across the Royal Women’s Hospital, Parkville and the University’s Parkville Campus.

PhD Scholarship Opportunity 2 – Elucidating the role of VEZT in human endometrium and endometriosis

About the Project
The human endometrium is a highly dynamic tissue that change’s structure, function and gene expression across the menstrual cycle.  Each cycle is made up of 3 specific phases, proliferative (repair and growth of the tissue), secretory (differentiation of the tissue) and menstruation (breakdown of the tissue).  At these three time points, a plethora of genes are up and down regulated, providing opportunity to evaluate genes essential to the regulation of each phase.  Endometriosis, a chronic and painful disease that impacts the lives of approximately 14% of women in Australia, is believed to develop from a process known as retrograde menstruation, where endometrial tissue is flushed through the fallopian tubes into the peritoneal cavity where it attached and grows.   Endometriosis is incurable in a majority of women, with limited non-invasive and non-hormonal treatments.  Over the last two decades, genome-wide association studies (GWAS) have identified several endometriosis risk associated genes with the single nucleotide polymorphism (SNP) rs10859871 having the strongest association. This SNP is upstream of the VEZT gene, leading to the identification of VEZT as a risk associated gene for endometriosis.  VEZT encodes an adherens junction protein (vezatin) which is critical to life, fertility, blastocyst formation, and sperm maturation.  Our research has also demonstrated functions in endometrial decidualisation, angiogenesis and inflammation and in our endometriosis mouse models, we have demonstrated a role in causal role in severe fibrotic endometriosis lesion formation.  This project will involve further exploration of the actions of VEZT overexpression in normal endometrial cells, organoids, endothelial cells and immune cells and the characterisation of endometriosis lesion formation, fibrosis development and pain induction in a unique mouse model of endometriosis followed by therapeutic interventions.  Our team has an exciting PhD opportunity for a multidisciplinary project which aims to evaluate the functional roles of VEZT overexpression in normal human endometrial tissue, cells and endometriosis lesion formation. 
The aims of the research are:

1. To develop several cell-based functional assays including endometrial epithelial organoids to demonstrate the unique functional and mechanistic properties of VEZT overexpression in endometrial function and endometriosis lesion formation.
2. To perform next gen sequencing (NGS) on cells overexpressing VEZT to identify novel genes involved in normal and abnormal cell function and to identify novel therapeutic targets in the case of abnormal cell function.

To translate and validate cell-based findings in a unique mouse model of endometriosis where VEZT is conditionally and ubiquitously overexpressed.

Supervision
The successful applicant will be supervised by:

• Jacqueline Donoghue, Senior Research Fellow and Project Lead, Gynaecology Research Centre, Department of Obstetrics, Gynaecology and Newborn Health
• Peter Rogers, Deputy Director of the Gynaecology Research Centre, Department of Obstetrics, Gynaecology and Newborn Health and Director of Research at The Royal Women’s Hospital,

The student will join the Gynaecology Research Group based at the Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne and will work across the Royal Women’s Hospital, Parkville and the University’s Parkville Campus.

Scholarship Benefits for both PhD Scholarship Opportunities

Scholarship benefits include:

• A stipend of $37,000 (2024 pro-rata rate, tax free), with possible extension to 3.5 years;
• Allowances as per the Graduate Research Scholarship Terms & Conditions.

A $5000 stipend top-up is available to those who are successful in being awarded Graduate Research Scholarship.

Eligibility for both PhD Scholarship Opportunities

Applicants should have:

• Honours or Master’s degree in science or biology or related field;
• Quantitative research experience.
• High academic marks that would meet eligibility for enrolment in a Research Higher Degree at the University of Melbourne and award of a scholarship.

Preference will be given to those who have:

• Experience in reproductive sciences, women’s health.
• Experience in working with animals, NGS,

This is a Full-Time role.

The scholarship is conditional upon acceptance into a PhD degree at the Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne. More information on MDHS requirements can be found here.

Applicants should be currently residing in Australia.

Download the EOI Application form

About the Gynaecology Research Centre
The Gynaecology Research Centre, situated at the Royal Women’s Hospital  and the Department of Obstetrics, Gynaecology and Newborn Health, University of Melbourne . The GRC aims to conduct research into several areas of benign gynaecology such as Endometriosis and Pelvic Pain, Heavy menstrual bleeding (HMB), Fibroids, Adenomyosis and Infertility along with malignant gynaecology such as Endometrial and Ovarian Cancer.  Our research is designed for clinically relevant and translatable outcomes for improved evidence based clinical trial development.  We perform both laboratory and clinically based research with strong connections between scientists and clinical teams at the Women’s and across the medical research precinct in Melbourne.