Japan_IPAP: Novel nanotechnologies for on-site expression and reconstitution of membrane-embedded machineries in synthetic cells

细胞是生命的基石。它们是在数十亿年的进化过程中被雕刻出来的，用于执行人类已知的一些最复杂的任务。然而，在它们的核心，它们可以被认为是一个相互作用的分子网络，尽管非常复杂。我们可以问自己：如果我们可以从头开始创造完全人工的细胞，结果会怎样？我们能用无生命的物质创造生命吗？实现这一雄心勃勃的目标将为颠覆性的应用奠定基础，并解决我们这个时代的一些重大社会挑战。构建一种新的生物学也将改变我们对生命系统的理解。人工细胞研究的最终目标是制造具有细胞生命标志性行为的人造微型机器人，包括移动、获取和隐藏能量、相互交流和与生物细胞交流、适应环境、复制、做出‘决定’、自我修复、生长、分裂甚至进化的能力。该领域的关键目标之一是设计能够通过遗传程序制造自己的机械的合成细胞，这将使它们能够自主。如果合成细胞要在学术环境之外作为治疗剂、药物发现、生物修复、传感和化学制造的工具应用，这是至关重要的。蛋白质是赋予细胞功能的分子机器。科学界现在广泛地能够设计出能够产生可溶性蛋白质的合成细胞，例如催化化学反应的酶。还有一种完全不同的蛋白质，由于技术限制，在自主合成细胞设计时是无法实现的：膜蛋白质。这是一个破坏性的瓶颈，因为这些蛋白质负责不同的细胞行为，从运动、通信和信号到能量产生、复制和细胞与细胞的黏附。在这个项目中，通过汇聚英国和日本的世界领先的研究人员，并结合我们在膜生物物理、分子生物学、DNA纳米技术和微流体方面的专业知识，我们将纠正这一疏忽。我们将进行可行性研究，以便设计和建造能够产生自己的基于膜的机械的合成电池。我们还将组织活动，将日本和英国充满活力的社区聚集在这一领域。如果科学界要实现工程合成生命的重大挑战，这种水平的国际合作和参与是必要的。

Cells are the building blocks of life. They have been sculpted over billions of years of evolution to perform some of the most complex tasks known to humankind. However, at their core, they can be thought of as a web of interacting molecules, albeit a very complex one. We can ask ourselves: what if we could create entirely artificial cells from scratch? Can we make life from inanimate matter? Achieving this ambitious objective will underpin disruptive applications and address some of the grand societal challenges of our time. Building a new biology will also transform our understanding of living systems.The ultimate aim of artificial cell research is to manufacture synthetic microrobots that possess the hallmark behaviours of cellular life, including the ability to move, harvest and covert energy, communicate with each other and with biological cells, adapt to the environment, replicate, make 'decisions', repair themselves, grow, divide, and even evolve. One of the key aims of the field is to engineer synthetic cells that are capable of making their own machinery from a genetic programme, which will allow them to be autonomous. This is critical if synthetic cells are to have applications beyond academic environments as therapeutic agents, tools in drug discovery, bioremediation, sensing and chemical manufacture. Proteins are the molecular machines that give cells their functions. The scientific community are now broadly able to engineer synthetic cells that can produce soluble proteins, such as the enzymes that catalyse chemical reactions. There is a whole other class of proteins that due to technological limitations, are out of reach when it comes to autonomous synthetic cell design: membrane proteins. This is a damaging bottleneck, as these proteins are responsible for diverse cellular behaviours, ranging from motility, communication and signalling through to energy generation, replication and cell-cell adhesion. In this project, by bringing together world-leading researchers in the UK and Japan, and combining our expertise in membrane biophysics, molecular biology, DNA nanotechnology and microfluidics, we will remedy this oversight. We will conduct the feasibility studies that enable the design and construction of synthetic cells that can generate their own membrane-based machinery. We will also organise activities to bring together vibrant communities in Japan and the UK in this space. This level of international cooperation and engagement is required if the scientific community is to achieve the grand challenge of engineering synthetic life.