Redirecting Cell Fate Through Epigenetic Reprogramming in Brain Cancer

About the research project

Medulloblastoma is the most common malignant paediatric brain tumour and remains a leading cause of cancer-related mortality in children. A defining feature of medulloblastoma is the high frequency of alterations affecting chromatin regulatory machinery. Recurrent mutations and structural abnormalities have been identified in genes encoding chromatin remodellers, histone modifiers and enhancer-associated regulatory complexes, including members of the SWI/SNF complex, KDM family demethylases, histone acetylation regulators, Polycomb proteins and other epigenetic regulators. These findings have led to the emerging concept that medulloblastoma is fundamentally an epigenetic disease, in which disruption of chromatin architecture and developmental gene regulation are primary drivers of tumour initiation, progression and therapeutic resistance.

The developing cerebellum is orchestrated by highly coordinated epigenetic programs that regulate lineage specification, differentiation and cellular maturation through dynamic changes in chromatin accessibility, DNA methylation and transcription factor activity. In medulloblastoma, these developmental trajectories become dysregulated, locking cells into aberrant progenitor-like states that sustain proliferation while preventing normal differentiation. Recent single-cell studies have revealed extensive epigenetic heterogeneity within tumours, with stem-like populations exhibiting chromatin landscapes reminiscent of embryonic cerebellar progenitors. These populations are thought to drive tumour growth, treatment resistance and recurrence. Importantly, unlike genetic mutations, epigenetic abnormalities are potentially reversible, creating an opportunity to therapeutically remodel chromatin architecture and redirect malignant cells towards differentiated, non-tumourigenic fates. However, the mechanisms through which chromatin remodelling controls medulloblastoma cell identity and plasticity remain poorly understood.

Our laboratory has developed cutting-edge single-cell epigenomic technologies capable of profiling chromatin accessibility, DNA methylation and transcriptional states at single-cell resolution. Combined with advanced computational approaches, these technologies enable the reconstruction of cellular trajectories and the identification of epigenetic mechanisms underlying tumour evolution and cell-state transitions.

This project will model the molecular evolution of medulloblastoma in human brain organoids and define how altered chromatin architecture drives tumour cell identity. Using live-cell imaging, single-cell multiomic profiling and next-generation sequencing technologies, the candidate will characterise dynamic cell-state transitions during tumour initiation and progression and identify the epigenetic mechanisms that underpin cellular plasticity. The project will further evaluate emerging inhibitors of chromatin remodelling proteins and targeted epigenetic perturbation approaches to determine whether malignant cells can be reprogrammed towards differentiated, non-tumourigenic states. These studies aim to establish proof-of-concept strategies for epigenetic reprogramming as a novel therapeutic approach for medulloblastoma while advancing our understanding of the molecular epigenetics that govern brain cancer development.

Primary supervisor

Meet Associate Professor Phillippa Taberlay

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

• a living allowance stipend funded by University of Tasmania of $34,315 per annum for 3.5 years
• a relocation allowance of up to $2,000
• a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Additional Funding

Applicants will have the opportunity to apply for additional funding including internal and external top-up and travel scholarships throughout their tenure

Other funding opportunities and fees

For further information regarding other scholarships on offer, and the various fees for undertaking a research degree, please visit our Scholarships and fees on research degrees page.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Ensure your eligibility for the scholarship round by referring to our Key Dates.

Selection criteria

The project is competitively assessed and awarded. Selection is based on academic merit and suitability to the project as determined by the College.

Additional essential selection criteria specific to this project:

• The project will require a strong background in molecular or cell biology, neuroscience and epigenetics.
• Applicants with a background in bioinformatics are strongly encouraged to apply.

Additional desirable selection criteria specific to this project:

• Experience with cell culture, particularly organoid cultures, would be an advantage.
• Bioinformatic data analysis will be an essential success criteria for this research project.

Application process

1. Select your project, and check that you meet the eligibility and selection criteria, including citizenship;
2. Contact Associate Professor Phillippa Taberlay to discuss your suitability and the project's requirements; and
3. In your application:
   • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
   • Submit a signed supervisory support form, a CV including contact details of 2 referees and your project research proposal.
4. Apply prior to 1 October 2026.

Full details of the application process can be found under the ' How to apply ' section of the Research Degrees website.

Following the closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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