Novel Synthetic Biology Approach to Monitor Transient Tumour-Immune Cell Interaction in vivo

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This project aims at monitoring the dynamic interactions between tumour cells and macrophages in cancer metastasis models, by combining synthetic biology and intra-vital imaging approaches.Metastasis, the spreading of tumour cells to secondary organs, accounts for over 90% of death from cancer and is the most pressing challenge for cancer research. Mounting clinical and preclinical evidences indicate that tumour/immune cells interactions have profound effects on cancer progression to metastasis (Kitamura et al., 2015). Previous studies have illustrated that tumour cells interaction with macrophages, a type of innate immune cells, is particularly critical for metastasis (Qian et al., 2011). The interaction is dynamic and complex, as there are different macrophage subsets with pro- or anti- tumour function differentially regulated by tissue microenvironment. Intra-vital imaging provides a powerful method to illustrate dynamic cell-cell interaction in relevant in vivo tissue environment. However, recording these transient interactions and interpreting their effect on disease progression has been challenging.Synthetic biology allows the engineering of new functions into cells through sensor and actuator synthetic systems. Recently, synthetic chimeric receptors have been developed and engineered in cells, to respond to contact with specific ligands presented on neighbouring cells (Morsut et al., 2016). In this project, new synthetic receptor cell lines will be developed to detect tumour cell interactions with different subsets of macrophages that bear distinct cell surface markers. These cells will report contact through fluorescent protein expression and allow real-time monitoring of macrophage/tumour cells interaction both in vitro and in mice cancer models, shedding light on the pivotal role played by these intercellular contacts in cancer progression. This project will provide novel insights into the disease mechanism and highlight potential therapeutic strategies to effectively treat this lethal disease.