Coles Group | Stromal and systems immunology
We take an interdisciplinary approach from single-molecule imaging to multi-scale computational modelling and experimental validation to identify and develop therapeutic strategies for immune-mediated inflammatory disease.
The stromal and systems immunology group uses interdisciplinary approaches from single-molecule imaging to multi-scale computational modelling to identify novel methods to therapeutically target immune-mediated inflammatory disease, develop optimal vaccination strategies and anti-tumour immunotherapies. This approach utilises a synergistic cycle of experimentation, data analysis and modelling combing data-driven modelling with mechanistic modelling and experimental validation. Outcomes are translated through experimental medicine basket trials and therapeutic development.
KEY RESEARCH FOCUS OF THE GROUP INCLUDE
1. Systems Immunology: Combining Mechanism Modelling with Machine Learning:
To identify mechanisms regulating immune function the laboratory applies a combination of mathematical and computational models, and machine learning-based approaches to identify and understand mechanisms driving immune efficacy and immune-mediated inflammatory disease (IMID) pathologies. Modelling based approaches permit testing of mechanisms driving human disease pathology in silico and applying genetic evolutionary algorithms to identify optimal solution sets and therapeutic intervention strategies. This has led to the development of virtual clinical trials to accelerate and de-risk translation from bench to bedside. We are utilising these to identify how immune microenvironments function as complex systems including understanding how receptor-ligand interactions, signalling pathways and metabolic products modulate immune function.
2. Stromal Immunology: Understanding localised immune microenvironments
Stromal fibroblasts have a key role in regulating immune responses through the production of cytokines, chemokines and metabolic products. In the laboratory we focus on mechanistic understanding of tissue fibroblast cell function in both lymphoid tissues and sites of pathology using a combination of single-cell gene expression, high-dimensional imaging, genetic reports and multi-dimensional flow cytometry. Areas of focus have included identifying the role of stromal fibroblasts in adjuvant function, identifying their role in regulating IMID progression, formation and resolution of tissue pathology and their role in regulating tumour progression including their role in regulating the type and duration of anti-tumour immune responses. One of the key aims of the group is to identify novel potential therapeutic targets expressed by stromal fibroblasts for therapeutic intervention including receptors, intracellular signalling molecules, stromal-derived cytokines and metabolic products
3. A 3Rs Research Framework: Applying 3Rs to Immune System Discovery and Development
Immunological research and the development of immunological therapeutics targeting IMIDs, cancer and infection uses large numbers of pre-clinical animal models. The aim of the laboratory is to develop new tools and guidelines to accelerate implementation of the 3Rs in immunological research potentially leading to a significant reduction in animal usage. These involve developing a framework of tools and methodologies to capture disparate data sets, evidence experimental design, model immune function and therapeutic interventions, and fully integrate and synergise experimental and computer models to increase therapeutic efficacy. We have developed a mathematical model to translate cell therapy dosing from mice to humans.