Projects
The Cancer Systems Microscopy Lab is engaged in key projects including diagnostic analysis of cancer patient-derived circulating tumour cell samples, development of new strategies for therapeutic lead / drug discovery, fundamental research into the composition, regulation and function of recently discovered Reticular Adhesions, and Proteomic Microscopy-based analysis of cell signalling systems.
Circulating tumour cell analysis for precision diagnostics
We aim to enable precision medicine by revolutionising analysis of signals driving cancer progression and therapy-resistance. We sample circulating tumour cells (CTCs) longitudinally and analyse them using Proteomic Microscopy, imaging up to 50 markers per CTC to quantify activity across multiple resistance-linked signalling pathways. Using multivariate statistics and artificial intelligence (AI), we classify resistant cancers by their signalling-drivers and train models to predict resistance mechanisms. This defines biomarker signatures with potential to stratify patients for targeted therapies. Beginning with prostate cancer, this precision diagnostic strategy is generalisable to many cancers.
Recent funding from the Tour de Cure Foundation was accompanied by a video explaining part of our approach to precision diagnostics development using liquid biopsy and systems microscopy:
Unbiased drug discovery for targeted therapy development
We have developed and tested a new strategy for drug lead-discovery that incorporates phenotypic screening of large-scale drug libraries (> 100, 000 compounds to-date) via high-throughput imaging, quantitative image analysis and multivariate statistical data analysis / machine learning to identify structurally and mechanistically diverse compounds with desirable biological effects. Already employed to explore the phenotypic plasticity of the actin cytoskeleton and at the same time identify new actin-regulating compounds, we are now working to generalise this approach in order to accelerate the discovery of lead compounds as part of the drug development pipeline.
Reticular Adhesions: characterisation & cellular functions
We recently led the discovery of a new cellular structure that we termed Reticular Adhesions. This integrin-mediated adhesion complex is found in a range of cell types, has a unique molecular composition, is regulated by phosphoinositide signalling and plays a novel role in the attachment of adherent cells to the extracellular matrix during mitosis. With this functional role important in the transmission of spatial memory between cell generations, and in the normal progression of cell division, we are now further exploring the dynamics, regulation, functional mechanisms and in vivo significance of Reticular Adhesions in health and disease.
Proteomic Microscopy analysis of subcellular signalling
Through sequential immunofluorescence multiplexing of subcellular signalling and regulatory protein markers, we aim to reconstruct signalling systems biology in situ within individual cells. Bridging the gap between computational systems biology modelling and the noisy complexity of signalling systems spatially distributed in heterogeneous cells, this approach has the potential to dramatically advance understanding of competitive signal regulation in the four dimensions of space and time. Retaining our focus on adhesion signalling biology in polarised and migrating cells, we will apply this approach to explore the fundamental processes and dynamics of cellular self-organisation.