失重环境下免疫细胞的损伤机制一直是空间生物学关注的重点问题之一。巨噬细胞在人体免疫过程中发挥重要作用。有文献指出，在空间失重环境下，巨噬细胞的形态以及细胞的力学特性（如细胞粘附力，迁移力等）均发生明显变化。然而，有关巨噬细胞核的力学性质以及细胞核内染色质（基因组）的三维结构是如何响应失重这一力学环境，包括基因组的三维结构是如何指导基因在特定空间和时间表达等机理，则少有研究涉及。“结构决定功能”是自然界规律的共识，最新的染色质构象捕获技术已经表明很多基因在线性基因组序列上虽然距离很远,但在空间结构上距离很接近。.因此，本项目拟从空间失重角度，以巨噬细胞为模型，通过原子力显微镜观测细胞核力学性质变化以及运用生物信息学中高通量染色质构象捕获技术，研究巨噬细胞的细胞核变化与免疫功能的关系，从细胞核力学性质与基因组的多维角度阐明空间失重环境下免疫细胞响应机制，为实时观测航天员的免疫反应提供理论依据。

Long-term space flight will be a major mission for China National Space Administration. However, microgravity is an issue for astronauts’ health. It has been shown that exposure to space flight result in immune system dysfunction. If this persists during flights, it could be a serious health risk to astronauts and crewmembers participating in lunar or Mars missions. Therefore, understand the mechanism of immune response under microgravity condition is a key topic.. Macrophage is one of the most important immune cells in human body. Its major function is phagocytosis that engulfs a solid particle or pathogen to form an internal compartment known as a phagosome. It has been reported that the biomechanics and immune function of macrophages were changed under microgravity condition. However, how the biomechanics of nucleus and the 3D genome changed under microgravity, still remains unclear.. In this project, we aim at obtaining the biomechanics of nucleus using atomic force microscopy and understand the 3D genome through High-throughput Chromatin conformation capture (Hi-C) technology which uses next-generation sequencing to sequence the whole chromatin and recover its structure information. Therefore, the chromatin structure will provide three-dimensional information on the gene regulation, in a better way to explain how the immune function dysregulated under microgravity. This research is the first one that focuses on nucleus, not only the biomechanics, but also three-dimensional genomic structure and provides the mechanism of immune response under microgravity condition.