The development of three dimensional (3D), spheroid or organoid cellular cultures for the study of cellular function, therapeutic development and biomarker discovery, has been the cornerstone of cancer research for many years. This is due to 3D structures demonstrating realistic biochemical and biomechanical activity that provides more physiologically relevant and predictive data for preclinical translating. The 3D structure provides mechanical and physiological barriers to drug entry that cannot be replicated in 2D format. Fortunately, many cancers cells will naturally form 3D shapes when cultured in specialised culture medias or on ultra-low attachment or cell-repelling surfaces. Unfortunately, many other cells that are associated with disease but are not cancer cells, will not naturally form spheroids or organoids and require extracellular matrices to support the development of a 3D structure. At present this is achieved using hydrogels like Matrigel but due to batch to batch variability in gel biochemistry and the temperature control requirements during plating, the practicality and reproducibility of high throughput screening using such gels is severely hampered. Therefore, to identify new treatments for non-cancer associated diseases, high throughput compound and molecular screening platforms require the development of 3D organoids in scaffolds that are non-biological, highly reproducible and temperature stable. These scaffolds also need to be suitable for miniaturisation into 384 or 1536 well format.
Our research priority is to find new therapeutics to target and eradicate the epithelial cells that establish endometriosis lesions. These lesions are non-malignant and non-life threatening but cause long term internal damage through repeated bleeding and wound repair. They also lead to infertility and chronic pain to sufferers. This research program has therefore been developed to assist with this priority through the evaluation and development of novel matrices, scaffolds and nanoparticles that will support the establishment of 3D structures for the purpose of High throughput compound and molecular screening.
Capabilities
- Tissue Culture facilities for 3D HTS model development
- Clinical specimens and bio-banked materials
- PC2 facility for transfection and model evaluation
- High throughput screening and high content imaging
- Pre-clinical models for drug evaluation and translation
- Next gene sequencing and Bioinformatics analysis
- Single cell, Spatial and Bulk Transcriptomics workflows
Impact
- Development of a reliable 3D HTS workflow using a highly reproducible and efficient scaffold will improve our understanding of endometriosis lesion formation and treatment
- This technology will also have significant impacts on other non-cancer associated diseases and will be applicable to other cell types
Program leader
Dr Jacqueline Donoghue