SpaceBiomechanics: Effects of microgravity on cell and tissue mechanics during wound healing

人类对地球以外存在生命的可能性着迷。在过去的几十年里，随着欧洲和英国航天局等机构的成立，全球在太空探索方面进行了大量投资。然而，尽管航天器工程正在改进，太空旅行的一个主要问题是重力降低对人类和其他生物体生物学的未知影响。如果我们想要维持地球以外的生命，这一知识是至关重要的。从细胞的角度来看，组织在微重力下所感受到的机械力是如何受到影响的？鉴于细胞的形状和功能是相关的，微重力如何改变细胞的形状，从而改变细胞的功能？关键是，在微重力条件下，组织修复严重受损，但机制原因仍不清楚。组织力学在航天创伤修复中起作用吗？为了解决这些问题，我将首先阐明3D细胞和组织力学在正常(地球)重力下伤口修复过程中的作用。然后，我将确定微重力在组织发育和动态平衡过程中如何影响细胞形状。最后，我将探讨细胞和组织力学在微重力下伤口修复中的作用。为了实现这一目标，我将结合先进的4D成像、图像分析技术、机器学习和计算机械模拟来分析果蝇翼盘在组织修复过程中的3D细胞形状和机械动力学。为了模拟微重力条件，我将使用地球上的随机定位机来培育苍蝇，使它们在微重力下发育和修复。总之，这项工作将阐明为什么组织修复在太空飞行过程中会中断，这将有助于开发治疗方法，以提高未来太空任务和地球以外生命的人类生活质量和寿命。我的研究计划，加上我提议的培训，将使我能够发展关键技能，开始我自己的空间生物医学实验室。

Humans are fascinated with the possibility of life beyond Earth. The last few decades have seen significant global investment in space exploration, with establishments such as the European and UK Space Agencies. However, even though space craft engineering is improving, one major problem with space travel is the unknown effects of reduced gravity on the biology of humans and other organisms. This knowledge is critical if we want to sustain life beyond Earth. From a cellular perspective, how are the mechanical forces experienced by tissues affected under microgravity? Given that cell shape and function are related, how is microgravity changing the shape, and therefore function, of cells? Critically, under microgravity conditions, tissue repair is severely compromised, yet the mechanistic reasons are still unknown. Does tissue mechanics play a role in wound repair during spaceflight? To address these questions, I will first elucidate the role of 3D cell and tissue mechanics during wound repair under regular (Earth) gravity. Then, I will determine how microgravity affects cell shape during tissue development and homeostasis. Finally, I will explore the role of cell andtissue mechanics on wound repair under microgravity. To achieve this, I will combine advanced 4D imaging, image analysis techniques, machine learning and computational mechanical simulations to analyse the 3D cell shape and mechanical dynamics of the Drosophila wing disc during tissue repair. To mimic microgravity conditions, I will use a Random Position Machine on Earth to grow flies, such that they develop and repair under microgravity. Altogether, this work will shed light on why tissue repair is disrupted during spaceflight, which will aid the development of treatments to improve the quality and longevity of human life on future space missions and life beyond Earth. My research plan, together with my proposed training, will enable me to develop the key skills to start my own Space Biomedicine lab.