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

这项NSF/CASIS在国际空间站（ISS）组织工程和力学生物学合作以造福地球生命的资助将支持新的研究，重点是了解组织的力学，如骨骼肌、骨骼和心脏，以响应微重力暴露或长时间的条件。太空旅行的进步和在火星或月球上建立定居点将需要人类长期暴露在微重力环境中。对宇航员和老鼠模型的研究表明，微重力会对身体器官产生负面影响，但具体是如何发生的尚不清楚。此外，地球上的病人可能会因器官退化而遭受骨骼和肌肉的损失。然而，驱动这些变化的潜在机制仍不清楚。利用在地面和国际空间站上的小鼠实验，该项目将研究机械卸载和微重力如何触发细胞核内部的变化，这些变化如何影响基因表达，以及这最终如何影响器官功能。新的药物干预将被开发，以减轻器官功能障碍，发生与微重力和去适应。本研究将以建立教育外展计划为基础，向K-12学生传播空间生物力学知识。该项目旨在发现组织水平的生物力学力和重力如何以细胞大小和组织类型依赖的方式维持染色质结构和基因表达。通过采用尖端技术，如高分辨率显微镜，先进的机械表征，分子生物学分析，小鼠模型和模拟微重力实验，研究人员旨在回答机械生物学中的几个突出问题。具体而言，该研究将探讨：1)生物力学和重力如何协同定义染色质结构和调节基因表达；2)太空飞行引起的染色质水平变化的改变是否主要是由空间重力改变或辐射暴露驱动的；3)是否可以通过药物干预来减轻航天和去适应引起的组织变性。该项目将使研究人员能够在染色质机械生物学、表观遗传学和基因表达机制等领域推进现有知识的边界。总的来说，这项研究的结果可能会影响人类太空旅行的未来，并有助于制定有效解决地球上患者器官功能障碍的策略。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.