The goal of this interdisciplinary project is to develop an experimental system for analysing cell-cell communication at the single cell level in the context of Oncogene Induced Senescence (OIS), a premalignant cell model. Non-autonomous activities of senescence, through senescence associated secretory phenotype (SASP) and cell-cell contact, reinforce and propagate the phenotype within the tumour microenvironment, potentially facilitating the malignant progression of ‘unstable OIS’ cells, depending on the cellular context.
Taking advantage of innovative microfluidic technology, our system would potentially offer a unique opportunity to gain a better understanding of the ‘very’ early history of tumorigenesis by directly visualising 1) how the OIS phenotype propagates across cells in different cellular contexts, and 2) how modulation of cell-cell communication affects the process.
In addition, the system will be optimised for single cell isolation compatible with RNAseq library preparation, opening the opportunity to generate data, effectively equivalent to ‘in situ RNAseq’. Such information would provide not only mechanistic insights into OIS/premalignancy development, but also new ‘context dependant OIS/premalignant biomarkers’.
Considering our recent data suggesting that the manipulation of the SASP program can enhance immune-mediated OIS cell clearance, our system would also help to identify targets for the ‘early treatment’ of premalignant cells.
Project lead: Dr Masashi Narita