Japan_IPAP: Engineering synthetic neuromuscular junctions to drive the autonomous function of biohybrid robots

自下而上的合成生物学旨在通过结合分子来模拟生物学中存在的结构、功能和包含信息的角色来重现细胞生物的结构和行为。这些结构被称为合成细胞，它们可以作为研究生物过程（如运动或复制）的框架，也可以作为微型试管，在其中可以进行化学和生化反应。在过去的5-10年里，合成细胞已经被开发出来，可以产生蛋白质生物分子，如果被活细胞感知，可以导致细胞行为的改变。因此，合成细胞和活细胞之间定义界面的组装可以控制生物系统，模仿生物突触中发现的组织，其中一个细胞靠近另一个细胞，促进细胞之间受控的化学信号传导。这种结构对于神经系统和肌肉之间的交流是必不可少的，在高级动物中，神经肌肉连接处（NMJ）的突触交流控制着肌肉的收缩。在生物学中，肌肉组织使动物能够移动和承担复杂的任务。这导致了工程肌肉组织在生物工程的另一个新兴领域的应用-生物混合机器人。生物杂交利用生物组件作为机器人的核心部分，例如控制肌肉组织的收缩，为能够拾取和释放物体的生物混合机器人提供动力。然而，激活机器人的传统方法依赖于使用电信号来激活肌肉收缩。虽然这导致成功激活，但这种方法会损害肌肉组织，限制机器人的使用寿命，并且在较大的生物混合设备中实施这种方法。该项目旨在组装合成细胞-肌肉组织界面，其中来自合成细胞的通讯蛋白Agrin的表达和释放导致肌肉组织中的蛋白质聚集，这对肌肉的最终收缩至关重要。通过这种方式，我们将利用生化方法来控制肌肉组织的收缩，首次形成合成神经肌肉连接点。这种连接可以作为研究生物学中突触组织的新模型，利用合成细胞共培养产生新的组织工程策略，并集成到生物混合机器人中，以创建具有更长的功能寿命的新一代先进生物启发机器人。为了实现这一目标，我们正在汇集英国和日本的世界领先的研究专业知识，以期汇集世界其他地方无法获得的专业知识：即Ces（合成细胞）和Takeuchi（生物混合系统）。

Bottom-up synthetic biology aims to reproduce the structures and behaviours of cellular organisms by combining molecules that mimic the structural, functional and information containing roles present in biology. These structures are known as synthetic cells, and they can act as a framework to study biological processes (such as movement or replication), as well as act as miniature test-tubes, within which chemical and biochemical reactions can be carried out.Over the last 5-10 years, synthetic cells have been developed that can produce protein biomolecules, that if sensed by living cells, can result in a change in cell behaviour. The assembly of defined interfaces between synthetic and living cells could therefore act to control biological systems, mimicking the organisation found in biological synapses where one cell is positioned close to a second, facilitating controlled chemical signalling between the cells. Such structures are essential for communication between the nervous system and muscles, where synaptic communication at the neuromuscular junction (NMJ) controls the contraction of muscles in higher order animals. In biology, muscle tissue enables animals to move and undertake complex tasks. This has led to the application of engineered muscle tissue in another nascent area of bioengineering - that of biohybrid robots. Biohybrids utilise biological components as a core part of the robot, for example controlling the contraction of muscle tissue to power a biohybrid robot capable of picking up and releasing an object. However, conventional approaches to activating the robot rely on using electrical signals to activate muscle contraction. Whilst this results in successful activation, this approach is damaging to the muscle tissue, limiting the lifetime of the robot and the implementation of this approach in larger biohybrid devices.This project aims to assemble synthetic cell - muscle tissue interfaces, where expression and release of a communication protein, Agrin, from synthetic cells results in protein clustering in the muscle tissue essential for the eventual contraction of the muscle. In this way we will utilise a biochemical approach to control the contraction of muscle tissue, forming for the first time a synthetic neuromuscular junction. Such junctions could be utilised as a new model to study synapse organisation in biology, lead to new tissue engineering strategies utilising synthetic cell co-cultures, and integrated into biohybrid robots to create a new generation of advanced bioinspired robots with increased functional lifetime.In order to achieve this we are bringing together world leading research expertise in the UK and Japan with a view to bringing together expertise not available in concert elsewhere in the word: namely Ces (synthetic cells) and Takeuchi (biohybrid systems).