MicroRNAs involved in neuroblastoma

About this project 

Neuroblastoma is the leading cause of cancer-¬related death in children under the age of five due to poor prognostic classification of tumours and a lack of targeted treatments. Current treatments rely mainly on damaging radiation and toxic chemotherapy, with poor cure rates and long-term risk of treatment-¬induced health problems. 

This project focuses on the critical role of microRNAs in neuroblast differentiation and neuroblastoma development. Neuroblastoma arises from a failure of cellular differentiation, where embryonic neuroblasts remain in a proliferative state. While microRNAs are known to be key regulators of cellular differentiation, their specific roles in neuroblast differentiation and neuroblastoma are poorly understood.

We have developed an innovative system using induced pluripotent stem cells (iPSCs) to model the differentiation of neuroblasts into sympathetic neurons. By leveraging both long and short-read RNA sequencing technologies, this system allows us to identify candidate microRNAs that drive this differentiation process, potentially acting as tumour suppressors in neuroblastoma.

As part of this project, you will implement a novel method for detecting microRNA activity in single cells. This approach will enable the identification of active microRNAs at each stage of neuroblast differentiation and their molecular targets. Additionally, you will conduct comprehensive bioinformatic analyses of microRNA targeting data to identify key regulators of differentiation and compare these findings to patient-derived microRNA sequencing data. The goal is to uncover microRNAs linked to disease outcomes, paving the way for improved prognostic tools and therapeutic strategies for neuroblastoma.

Join us in advancing the understanding of neuroblastoma biology and contributing to the development of innovative treatments for this devastating childhood cancer.

What you’ll do 

This project-based research degree offers a unique opportunity to conduct cutting-edge laboratory, bioinformatics, or hybrid research under the guidance of an expert supervisory team. For the right candidate, the approach can be tailored to align with your expertise and interests.

This may include:

• Bioinformatics Analysis: Develop a novel computational method to detect miRNA activity at a single cell resolution and integrate it with data from our iPSC system to analyse and interpret changes in miRNA targeting during cellular differentiation. Compare patient-derived datasets to identify miRNAs influencing neuroblastoma outcomes and refine tumour classifications at the molecular level.
• Laboratory Research: Work with our innovative induced pluripotent stem cell (iPSC) model to explore the differentiation of neuroblasts into sympathetic neurons. Apply long- and short-read RNA sequencing to identify key microRNAs (miRNAs) and their molecular targets, and validate candidate drivers using CRISPR approaches to confirm their roles in neuroblast differentiation and disease subtypes.

This project will provide hands-on experience with cutting-edge stem cell models, RNA sequencing technologies, and advanced bioinformatics tools. By identifying and validating miRNA drivers of differentiation and correlating findings with neuroblastoma cytogenetic subtypes, this work will contribute to refining tumour classification and enhancing our understanding of neuroblastoma biology. You’ll gain the skills to make a meaningful impact on neuroblastoma research and RNA-based therapeutic 

Where you’ll be based 

The Centre for Cancer Biology within UniSA is a hub of cancer research within the state, and boasts the largest concentration of cancer research in South Australia, currently hosting 22 full-time research group leaders and their teams. CCB laboratories carry out research in many cancers, as well as fundamental cell biology, focussing in the specialised areas of gene regulation, molecular signalling, translational oncology and genomics, performing high impact, fundamental and applied research that is internationally recognised. 

This proposed research will directly contribute to the cancer key research theme at UniSA. The project aligns with and extends two MRFF grants held jointly by the supervisors. The project aims to contribute to improved health outcomes for children. The candidate will be working in the Gene Regulation Section of the Centre for Cancer Biology under the direct supervision of the Section head, Prof Greg Goodall, FAA, FAHMS. The section encompasses approximately 15 researchers, including several PhD and honours students. 

The Centre for Cancer Biology is a collegial and friendly working environment, fully equipped with state of the art technologies and staffed by passionate researchers whose skills range from cell biology through to the bioinformatic analysis of high throughput genomic sequencing. The student will have access to a wide range of training and career development opportunities including a networking with national invited speakers at the precinct-wide cancer research seminar series. The Centre for Cancer Biology is located within the Bradley Building at UniSA (City West campus). Financial Support  

This project is funded for reasonable research expenses. Additionally, a living allowance scholarship of $35,200 per annum is available to Australian and New Zealand citizens, permanent residents of Australia. Australian Aboriginal and/or Torres Strait Islander applicants will be eligible to receive an increased stipend rate of $52,352 per annum (2025 rate). A fee-offset or waiver for the standard term of the program is also included for this group. For full terms and benefits of the scholarship please refer to our scholarship information. International applicants will not be eligible to receive the scholarship.

Eligibility and Selection 

This project is open to applications from both Domestic and International applicants. Applicants must meet the eligibility criteria for entrance into a PhD. 
Additionally, applicants must meet the project selection criteria: 

• An honours or masters degree or equivalent research experience in molecular/cellular biology, bioinformatics or a related discipline.

The following would be beneficial, please include details on any background or experience in the following:

• Prior research experience in genetics or molecular biology
• Experience in RNA biology, transcriptomics and/or cancer biology 
• Experience analysing large-scale sequencing data
• Computational skills or experience and level of proficiency, including in programming in R, python and/or bash or working in Linux or HPC environments.

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 to be based at our City West Campus in the heart of Adelaide. Note that international students on a student visa will need to study full-time.

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 18 December 2024.