Project title
Uncovering the Role of Transposable Elements in Melanoma Progression and Therapy Response Using Long-Read Sequencing
Collaborators and funding
Peter MacCallum Foundation Grant
Contact(s)
- Associate Professor Karen Sheppard, PhD, Principal Research Fellow Peter MacCallum Cancer Centre Sir Peter MacCallum Department of Oncology, University of Melbourne, karen.sheppard@petermac.org
- Lorey Smith, PhD, Victorian Cancer Agency Mid-Career Fellow, Molecular Oncology Laboratory, Peter MacCallum Cancer Centre, Lorey.Smith@petermac.org
Project description and aims
- Aim 1: Profile differential expression of TEs using long-read RNA sequencing
- Utilize long-read RNA sequencing to capture full-length TE transcripts in melanoma samples across different therapy responses and disease stages.
- Aim 2: Identify TE insertions affecting gene regulatory networks
- Employ long-read DNA sequencing to map TE insertions and assess their impact on transcription factor binding sites and gene expression.
- Aim 3: Investigate TE-associated splicing events and mutations
- Analyze long-read sequencing data to detect alternative splicing events and mutations associated with TE activity.
- Aim 4: Discover TE-based biomarkers for therapy response and metastasis
- Integrate TE expression, insertion, and methylation data to identify potential biomarkers predictive of treatment outcomes and disease progression.
How is ABLeS supporting this work?
This work is supported through the Production Bioinformatics scheme provided by ABLeS.
Expected outputs enabled by participation in ABLeS
This project is designed to provide deep biological insight into how TEs contribute to melanoma relapse and progression by integrating expression, insertion, and epigenetic profiles.
- Human Tumours: - Identify TE insertions enriched in metastatic vs. primary tumours - Detect hypomethylated TE loci specific to aggressive disease - Discover prognostic biomarkers for early metastasis potential
- Mouse Models:
- Capture the trajectory of TE activation over therapy timepoints
- Map regulatory switch points mediated by TE insertions
- Define temporal TE signatures linked to immune evasion and residual disease
- Cell Lines:
- Characterize baseline TE insertion and expression differences in resistant vs. sensitive lines
- Validate TE-gene chimeras and novel isoforms as resistance markers
This study will allow us to obtain:
- High-resolution atlas of TE insertions across melanoma evolution
- Functional annotation of TE-induced regulatory network disruptions
- Novel isoforms and splicing events linked to TE insertions
- Candidate TE biomarkers and druggable targets, including expressed HERV elements or hypomethylated LINE-1s
- Publicly accessible database of melanoma-specific TE activity (available to Peter Mac and broader research community)
These details have been provided by project members at project initiation. For more information on the project, please consult the contact(s) or project links above.