Cellular parabiosis: the role of cell-to-cell communication in phenotypic suppression

Croatian Science Foundation (2020-2023)

Coordinator: MedILS (lead Katarina Trajković)

Partners: Nortwestern Univesity, IRB

Healthy aging is one of the most important goals of the contemporary society from the medical and economical perspectives. Thus, major research efforts are directed towards identifying molecular mechanisms of aging with the aim to develop strategies for attenuating aging. The main objective of our proposed project is to tackle promising, but insufficiently explored concept that cell-to-cell communication plays an important role in delaying onset of age-related diseases. We aim to unambiguously demonstrate and describe mechanistically the phenomenon of phenotypic suppression of individual cells' dysfunction by the healthy subpopulation of surrounding cells, a process which we refer to as cellular parabiosis. To that end, a subpopulation of cells with various aberrant phenotypes will be grown in monocultures or in co-cultures with intact, healthy cells, and their phenotypes under these two conditions will be assessed and compared using fluorescent microscopy and flow cytometry. Aberrant phenotypes will be initiated before coculturing by oxidative and proteotoxic stress, DNA-damaging radiation, by allowing cells to reach senescence or by genetic mutations underlying Niemann Pick type C neurodegeneration. Furthermore, DNA damage will be triggered directly in preexisting co-cultures using X-ray microbeam. We expect to detect amelioration of aberrant phenotypes in affected cells grown in co-cultures as compared to those grown in monocultures. Finally, we will identify cell-to-cell communication tools mediating cellular parabiosis in relation to specific
aberrations. Clear demonstration and mechanistical description of the central role of cellular parabiosis as a natural protective principle will open possibilities for development of an innovative approach to prevention of multiple age-related phenotypes taroetino cell-to-cell communication.