ISS: Effect of Microgravity and Mechanical Deconditioning of Tissues on the Chromatin, Epigenetic Alteration, and Multiscale Biomechanics

Colorado State University, Fort Collins CO

Investigators

Abstract

This NSF/CASIS Collaboration on Tissue Engineering and Mechanobiology on the International Space Station (ISS) to Benefit Life on Earth grant will support new research focused on understanding the mechanics of tissues, such as skeletal muscle, bone, and heart, in response to microgravity exposure or prolonged deconditioning. Space travel advancements and establishing settlements on Mars or the Moon will require prolonged human exposure to microgravity. Studies on astronauts and mouse models have shown that microgravity can negatively affect organs in the body, but precisely how this happens is unknown. Additionally, patients on Earth can suffer from bone and muscle loss due to organ deconditioning. However, the underlying mechanisms driving these changes remain unclear. Utilizing experiments in mice on the ground and in International Space Station, this project will investigate how mechanical unloading and microgravity triggers changes inside the cell nucleus, how these changes influence gene expression, and how this ultimately affects organ function. Novel pharmacological interventions will be developed to mitigate organ dysfunction that occurs with microgravity and deconditioning. This research will be complemented by establishing an educational outreach program based on disseminating space biomechanics knowledge to K-12 students. This project seeks to discover how the biomechanical force at the tissue level and the gravitational force maintain the chromatin architecture and gene expression in a cell size and tissue type-dependent manner. By employing cutting-edge techniques such as high-resolution microscopy, advanced mechanical characterization, molecular biology assays, mouse models, and simulated microgravity experiments, the researchers aim to answer several outstanding questions in mechanobiology. Specifically, the study will investigate: 1) how biomechanical and gravitational forces collaboratively define chromatin architecture and regulate gene expression; 2) whether spaceflight-induced alterations in chromatin level changes is primarily driven by altered gravitational force or radiation exposure in space; and 3) whether pharmacological interventions can be used to mitigate tissue degeneration caused by spaceflight and deconditioning. This project will enable researchers to advance the boundaries of the existing knowledge in the fields of chromatin mechanobiology, epigenetics, and gene expression mechanisms. Overall, the outcome of this study might influence the future of human space travel and contribute to the development of strategies for effectively addressing organ deconditioning in patients on Earth. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.