Project MicroAge: A tissue engineered discovery platform for improving muscle responses to exercise in ageing and spaceflight

Project MicroAge：一个组织工程发现平台，用于改善衰老和太空飞行中肌肉对运动的反应

• 批准号: 2601024
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2601024
• 关键词: Project; MicroAge; tissue; engineered; discovery

Summary: Astronauts lose muscle mass despite performing considerable exercise in space, since their cellular adaptation to exercise is somehow abnormally impaired by microgravity. On Earth, our muscles also respond less well to exercise as we get older, resulting in reduced muscle mass, loss of strength and frailty.Our team have demonstrated that reactive oxygen species (ROS) generated during exercise stimulate the activation of specific transcription factors which increase the production of cytoprotective proteins. However, these responses are impaired in muscle from older humans, and analogously may also be attenuated in astronauts in microgravity. This comparison is the basis for our current research at MicroAge, and to do this we have constructed an experimental bioreactor that will soon fly on the International Space Station. The bioreactor uses an 'organ-on-a-chip' type technology to support bioengineered micro-muscles created from human cells, with microfluidic plumbing to refresh nutrients and collect secreted biomolecules, and an electrical stimulation circuit to enable the micro-muscles to undergo contractile exercise.One of our goals is to discover drugs which correct the faulty signalling, since these will help us maintain muscle mass as we age and will enable longer-duration (e.g. interplanetary) spaceflight missions. As part of our team, you will use our existing muscle bioreactor to investigate interventional drugs that can restore the ability of human muscle to respond to exercise during ageing (or in spaceflight). Your initial project goals will be:1. To determine key biomarkers (cytokines, myotube diameter, mitochondrial respiration rate, force generation, etc.) and develop practical methods to measure them.2. To test the effectiveness of novel drugs, nutritionally-derived supplements, and gene/cell therapies to recover and rescue the phenotype of aged muscles.You will get training in a wide range of interdisciplinary skills (how biology interfaces with mechanical and electrical engineering), learn how we translate basic scientific discoveries into therapeutics, and develop highly valuable quantitative skills. The project links biology across multiple scales: from biochemical signals, through organelles and cells, to visible changes is tissue function. The collaboration with industry and our ongoing acquisition of multidimensional data from ISS microgravity experiments gives you a unique opportunity for developing new technology and underpinning world-leading scientific advances.The DTP will enable you to work closely with our project partners at the UK Space Agency and Kayser Space Ltd., expanding our existing technology from a specific spaceflight application to a broader range of investigative uses in discovery medicine. Kayser have extensive experience of designing and manufacturing miniaturised bioreactor systems and will help you design, manufacture and test new hardware using commercially appropriate techniques and ISO/QA standards. You will also be encouraged to develop your skills in science commination via the UKSA and our exciting outreach programme involving patient groups, schools and the local community, and take charge of updating our interactive project app to support public awareness of our research.

摘要：尽管宇航员在太空中进行了大量的运动，但他们的肌肉质量仍在下降，因为他们对运动的细胞适应在某种程度上受到微重力的异常损害。在地球上，随着年龄的增长，我们的肌肉对运动的反应也会减弱，导致肌肉质量减少、力量丧失和虚弱。我们的团队已经证明，运动中产生的活性氧物种(ROS)可以刺激特定转录因子的激活，从而增加细胞保护蛋白的产生。然而，这些反应在老年人的肌肉中受到了损害，同样地，宇航员在微重力下也会受到削弱。这种比较是我们目前在MicroAge进行研究的基础，为了做到这一点，我们建造了一个即将在国际空间站飞行的实验生物反应器。这种生物反应器使用了一种“芯片器官”式的技术来支持从人类细胞中产生的生物工程微型肌肉，通过微流控管道来更新营养并收集分泌的生物分子，以及一个电刺激电路来使微型肌肉进行收缩锻炼。我们的目标之一是发现纠正错误信号的药物，因为这些药物将帮助我们随着年龄的增长保持肌肉质量，并将使我们能够进行更长时间(例如星际)的太空飞行任务。作为我们团队的一部分，您将使用我们现有的肌肉生物反应器来研究介入性药物，这些药物可以恢复人体肌肉在衰老期间(或在航天中)对运动的反应能力。你最初的项目目标是：1.确定关键的生物标志物(细胞因子、肌管直径、线粒体呼吸速率、力量产生等)。并开发实用的方法来测量它们。为了测试新药、营养补充剂和基因/细胞疗法恢复和挽救衰老肌肉表型的有效性，你将接受广泛的跨学科技能培训(生物学如何与机械和电气工程相结合)，学习如何将基本科学发现转化为疗法，并发展非常有价值的量化技能。该项目将生物学联系在多个尺度上：从生化信号，到细胞器和细胞，再到可见的变化是组织功能。与业界的合作以及我们正在从ISS微重力实验中获取多维数据，为您提供了开发新技术和支持世界领先的科学进步的独特机会。DTP将使您能够与我们在英国航天局和Kayser Space Ltd.的项目合作伙伴密切合作，将我们现有的技术从特定的航天应用扩展到更广泛的发现医学研究用途。Kayser在设计和制造微型生物反应器系统方面拥有丰富的经验，并将帮助您使用商业上合适的技术和ISO/QA标准设计、制造和测试新硬件。我们还将鼓励您通过UKSA和我们令人兴奋的外展计划(涉及患者团体、学校和当地社区)发展您的科学合作技能，并负责更新我们的互动项目应用程序，以支持公众对我们的研究的认识。