Mode
Internal

Study As
Full Time

Principal Supervisor
Professor Janna Morrison

Main Campus
City West

Applications Close
29 Jan 2023

Study Level
PhD or Masters by Research

Applications Open To
Domestic Candidate

Tuition Fees:
All domestic students are eligible for a fee waiver. International students who receive a stipend are eligible for a fee waiver. Find out more about fees and conditions.

Project Stipend:
$29,863 p.a. available to domestic applicants only

About this project

Develop novel preterm birth interventions using the glucocorticoid prodrug ciclesonide

Are you passionate about a career in biomedicine and keen to develop novel preterm birth interventions? The University of South Australia – Australia’s University of Enterprise – is offering a ground-breaking project-based research degree with real-world application within our Health and Biomedical Innovation (HBI) research group.

Maternal antenatal corticosteroids (ACS) promote fetal lung maturation, reduce respiratory distress syndrome and improve survival of preterm babies. They are routinely administered to women at risk of delivering preterm. However, despite their recognised benefits, clinicians are becoming increasingly concerned about adverse effects.

Once transferred across the placenta to the fetal circulation, ACSs initiate GR signalling in all fetal tissues. Although this benefits the lungs, ACSs also acts off-target. Most concerning is the neurodevelopmental consequences of brain GR activation. We need a new therapy that activates the GR in fetal lungs but not the brain.

Ciclesonide is a synthetic corticosteroid prodrug with very low GR affinity unless activated to des-ciclesonide by carboxyl esterase (CES) enzymes. Inhaled ciclesonide is rapidly converted to des-ciclesonide in human lungs, increasing its GR-binding affinity a hundred-fold, and des-ciclesonide persists in lung tissue for over 8 hours. Cytochrome P450 3A4 mediates rapid hepatic clearance of circulating des-ciclesonide (>99% first-pass metabolism) which, together with its retention in the lungs, minimises off-target activity of inhaled ciclesonide.

What we don’t yet understand is whether ciclesonide metabolism is altered during normal and complicated pregnancies, and the potential implications of using ciclesonide to mature the fetal lungs before preterm delivery. 

Our project seeks to determine the activity of the enzymes that metabolise ciclesonide in pregnant vs nonpregnant female adults and examine the maternal and fetal tissues in normal and complicated pregnancies. We will use tissues from a range of clinical and preclinical cohorts in humans, baboons, guinea pigs, mice and sheep.

You will have access to the breadth of experience within the Health and Biomedical Innovation (HBI) group. Our well-established laboratories offer state-of-the-art equipment and facilities and you will be trained by a team of experts in a variety of procedures.
Through our funded projects (ARC DP, MRFF, Channel 7 and NHMRC Ideas), you will have the unique opportunity to work with human placenta samples while also gaining experience with a large animal model of pregnancy. This means participating in fetal surgery, postoperative care, fetal cardiac MRI and tissue collection.

UniSA’s partnership with SAHMRI in the preclinical imaging and research laboratories, where the animal studies will be performed, will give you exclusive access to surgical theatres, long-term animal housing, CT and MRI facilities. This is an exciting opportunity for you to access a BioBank of fixed and frozen tissue with extensive clinical records and in vivo physiological data.

What you’ll do

In this project-based research degree, you will undertake computer and lab work, and spend time in the animal house. You will participate in fetal surgery, post-operative care, blood pressure studies and tissue collection. You will perform LC-MS/MS assays to determine activity of CES and CYPs in the maternal and fetal liver as well as the placenta. 

Other tasks include analysing data using Microsoft Excel and Prism and using real-time PCR and Western blotting to study CES, CYP and drug transporter gene and protein expression. You will also be trained in how to use LC-MS/MS assays to measure fetal plasma hormones and CYP substrates and metabolites.

You will be supported to disseminate findings via scientific journals and through attending conferences. There is the opportunity to attend conferences locally (e.g., HBI Trainee Symposia), nationally (e.g., Cardiac Society of Australia and New Zealand), and internationally (e.g., Fetal and Neonatal Physiological Society). 

Upon completion of your studies, you will possess a range of transferable skills including in designing studies, organising long-term projects, working productively in an independent and a team environment, communicating effectively with scientists from a range of disciplines (fetal physiology, pharmacology, pharmaceutical sciences, endocrinology), performing experimental work, and writing for science.

Where you’ll be based

You will be based within the Health and Biomedical Innovation group. We study the complex workings of the body and its interaction with environment. Our goal is to address fundamental questions about how the body and its environment work and to integrate this knowledge to increase our understanding of the human body as a whole, in both health and disease. This approach involves measuring changes in the body with disease and the impact of interventions and allows us to discover biomedical pathways to improve health while providing the foundational knowledge required for translation into clinical practice. We achieve this through initiating, and being sought for engagement with, strong partnerships with other national and international thought leaders in academia, clinical practice, industry, government and our community. 

Our work is disseminated through production of high-quality publications, engagement with end-users and the community at conferences and with public presentations. Our fundamental approach to science provides a strong basis for student engagement across all health science programs, integrating our research into our teaching practices to develop industry ready graduates and engage them in our research endeavours.
Our research pillars represent a new direction in health and chronic disease research, focusing on strong engagement with government, industry, regulatory bodies, policy-makers and the community.

Supervisory Team


Financial Support

This project is funded for reasonable research expenses. Additionally, a living allowance scholarship of $29,863 per annum is available to Australian and New Zealand citizens, and permanent residents of Australia, including permanent humanitarian visa holders. Australian Aboriginal and/or Torres Strait Islander applicants will be eligible to receive an increased stipend rate of $46,653 per annum (2023 rates). A fee-offset or waiver for the standard term of the program is also included. For full terms and benefits of the scholarship please refer to our scholarship information. International applicants are not invited to apply at this time.

Eligibility and Selection

This project is open to applications from Australian or New Zealand citizens, and Australian permanent residents or permanent humanitarian visa holders. International applicants are not invited to apply at this time.

Applicants must meet the eligibility criteria for entrance into a Masters or PhD. All applications that meet the eligibility and selection criteria will be considered for this project. A merit selection process will be used to determine the successful candidate.

The successful applicant is expected to study full-time and be based at our City West Campus in the heart of Adelaide.

Essential Dates

Applicants are expected to start in a timely fashion upon receipt of an offer. Extended deferral periods are not available. Applications close on Sunday 29 January 2023.

How to apply:

Applications must be lodged online, please note UniSA does not accept applications via email.

For further support see our step-by-step guide on how to apply , or contact the Graduate Research team on +61 8 8302 5880, option 1 or email us at research.admissions@unisa.edu.au. You will receive a response within one working day.

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