This work package aims to leverage the powerful systems microscopy tools developed within the consortium in specific translational applications, such as exploration and diagnosis of the dependency of cancer on specific targets, or reactivity towards specific drugs. Furthermore, we will also validate the in vivo relevance of the systems biological models and findings obtained in WPs 1 and 2, using pre-clinical mouse models and clinical cancer data.
More specifically, the objectives and steps are as follows:
1) Select for further study and validation the most exciting systems biological models, such as specific genes involved as key regulators of specific types of mitotic and migratory behaviour, arising from the systems microscopic analysis and modelling in this NoE.
2) Analyze and validate cell migration-associated systems biological models and key genes in animal model systems in vivo, using intravital two-photon imaging.
3) Develop a translational systems biology pipeline, linking the in vitro and in vivo systems microscopic findings with bioinformatic and literature data, as well as validation of the profiles of the key targets in clinical samples.
4) Demonstrate, in proof-of-concept (POC) studies, the power of systems microscopic techniques (such as cell microarrays, live-cell multi-parametric imaging, or 3D cell culture model systems) in testing predictors of cancer cell responsiveness to siRNA and drug treatment in vitro.
This would provide an example of future diagnostic approaches to test the dependency of tumours on individual genes and pathways identified in this study. We believe and plan to demonstrate that the key advantages of systems microscopy, such as the ability to look at individual cells over time, will be helpful in understanding cancer heterogeneity, dependency of cancers on specific targets, as well as the variability of drug response. The POC studies are designed to demonstrate these exciting possibilities for translational research.
Olli Kallioniemi (WP leader)