Development of microscopy-based tools for deciphering role of integrin-based signaling heterogeneity in cancer

The most important reason cancer kills is the generation of metastatic cells and their subsequent spread from the primary tumor site. If those mechanisms could be resolved in single cells, we could improve treatments. There are several issues: a) cancer cells are diverse, and we lack good ways to study single-cell heterogeneity functionally, b) we lack good tools to monitor molecular signaling, c) we lack approaches to relate single-cell signaling to a cell population. Here, to solve these issues, we will build and develop novel tools for automated and quantitative high- resolution live microscopy of migrating cancer cells. The aims are:
(1) to further develop our data-driven microscopy platform, where the microscope can automatically acquire high- resolution single-cell time-lapse data of phenotype-specified target cells identified by population screening.
(2) to build fluorescent integrin biosensors, where the sensors can relay information on timing, localization, and magnitude of integrin signaling during cell migration.
(3) to apply the above technologies in live cancer cell migration experiments, where molecular single-cell data can be collected in a population-wide manner allowing for mechanistic deciphering of single-cell heterogeneity in the context of cell migration.
We believe that we will contribute with new technology and knowledge that will advance the field of cancer biology and lead to better-targeted treatments for integrin-mediated cancer mechanisms.