Research Summary

Mechanobiology of cell competition: Elucidating the role of mechanical forces in cell-cell sensing and collective fitness measurement towards tumor suppression in epithelial tissues

Mutations in the genetic material can have devastating consequences on the integrity of our tissue and organ systems. If remain undetected, mutated cells can compromise the tissue fitness and serve as the cradle for cancer formation. It is, therefore, essential to understand how the tissues in our body, especially the epithelial tissues, maintain their fitness for a considerably long period, in face of incessant spouting of mutated cells. In this respect, cell competition is a fundamental fitness-sensing process. Through cell competition, which is also known as the epithelial defense against cancer, normal healthy cells detect and eliminate the unfit cells. In our group, we are trying address some of the most critical but unresolved questions related to cell competition such as: How do the cells measure the fitness of their neighbors? What do they effectively measure? And how does the fitness-measurement determine the cellular fate? To this end, we are undertaking an interdisciplinary approach, in which measuring forces at the cell-cell and cell-matrix junctions becomes central. Ultimately, we would intend to combine the mechanobiology tools of our laboratory with the conventional molecular biology techniques to elucidate the molecular mechanisms and possibly the guiding principles of cell competition.

Figure Legend: The image depicts how mutant and potentially tumor forming cells expressing an oncogenic version of Ras proteins (green) are physically compacted before getting eliminated by the surrounding wild type cells that do not express this protein. Cell nuclei are shown in red. Image size is 164 ?m X 164 ?m.