21ENGBIO A Universal and Controllable Interface between Synthetic Cells and Living Cells

21ENGBIO 合成细胞和活细胞之间的通用且可控的接口

• 批准号: BB/W011468/1
• 负责人: Michael Booth
• 金额: $ 12.84万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW011468%2F1
• 关键词: 21ENGBIO; Universal; Controllable; Interface; between

A growing area of research is the creation of 'synthetic cells' from discrete building blocks. Through this research we can gain an understanding of how life started and evolved. Additionally, as synthetic cells are completely modular and cannot self-replicate, they offer promise as novel drug delivery systems and as tools to interface living and non-living materials. These interfaces might be used to study or modify living tissue, without the need for genetic modification. Approaches to interface synthetic cells with living cells often arise from mimicking specific processes in living cells, without other competing processes. However, currently there are no universal methods to allow synthetic cells to communicate with living cells using a wide range of signal molecules. For instance, the two most common approaches rely on identifying signal molecules that will move across the synthetic cell membrane by themselves, or the use of proteins that form holes in the membranes. However, beyond not being universal, both approaches have significant downsides and limitations. We will generate a method that allows the release of any-sized signal molecule. This will be a step change in the use of synthetic cells as research tools and drug delivery devices. Our approach will mimic the communication of neurons in the brain. Neurotransmitters are held within neurons in small compartments. Release of neurotransmitters at the synapse is achieved by the fusion of these small compartments to the cell membrane, by forcing them together. We will generate synthetic cells that contain small compartments. These small compartments will be able to be filled with any-sized signal molecule. Fusion of the small compartment to the synthetic cell membrane, like is seen in neurons, will be initiated by using a mix of DNA and RNA strands. DNA and RNA complementarity is ideal for this function as it is strong and programmable. By incorporating functional signal molecules within the small compartments, we will then interface these synthetic cells with neighbouring living cells to control their function.For real world application, the function of synthetic cells needs to be triggered, ideally with a remote stimulus, to inhibit the synthetic cell activity where it is not wanted. Light is an ideal stimulus as it can be applied remotely at a precise point in space and time. To achieve this, we will incorporate a light-activated template that the synthetic cells with function from, which we have previously generated.Our method to interface synthetic and living cells will be universal and remote controllable. By encapsulating neurotransmitters within the small compartments, this externally controlled release might be used as a computer-brain interface between synthetic cells and neurons. Additionally, as any molecule could be encapsuled in the synthetic organelles and released with light, there is the potential for precision drug targeting to any living cell. This basic research project to broaden the functionality of synthetic cells has the potential to revolutionise the research area and bring about the real-world potential of synthetic cells.

不断增长的研究领域是从离散构建块创建“合成细胞”。通过这项研究，我们可以了解生活的开始和发展。此外，由于合成细胞是完全模块化的，并且不能自我复制，因此它们作为新型药物输送系统和界面生活和非生存材料的工具提供了希望。这些界面可用于研究或修饰活组织，而无需遗传修饰。与活细胞合成细胞界面合成细胞的方法通常是由于模仿活细胞中的特定过程而没有其他竞争过程。但是，目前尚无通用方法，可以使用多种信号分子与活细胞与活细胞进行通信。例如，这两种最常见的方法依赖于识别信号分子，这些信号分子本身会在合成细胞膜上移动，或者使用在膜中形成孔的蛋白质。但是，除了没有普遍性外，这两种方法都具有明显的弊端和局限性。我们将生成一种允许释放任何大小信号分子的方法。这将是使用合成细胞作为研究工具和药物输送设备的步骤变化。我们的方法将模仿大脑中神经元的交流。神经递质在小隔室的神经元内举行。神经递质在突触中的释放是通过将这些小隔室融合到细胞膜来实现的。我们将生成包含小隔室的合成细胞。这些小隔室将能够用任何大小的信号分子填充。小室与合成细胞膜的融合（如在神经元中所见）将通过使用DNA和RNA链的混合物来启动。 DNA和RNA互补性是此功能的理想选择，因为它是强大且可编程的。通过将功能信号分子纳入小隔室，我们将与邻近活细胞连接这些合成细胞以控制其功能。对于现实世界的应用，需要触发合成细胞的功能，理想地使用远程刺激，以在不需要的情况下抑制合成细胞活性。光是一种理想的刺激，因为它可以在空间和时间的精确点上远程应用。为了实现这一目标，我们将结合一个带有功能的合成细胞与以前生成的光激活模板。我们的接口合成方法和活细胞的方法将是通用且遥控的。通过将神经递质封装在小室内，该外部控制释放可以用作合成细胞和神经元之间的计算机脑接口。此外，由于任何分子都可以封装在合成细胞器中并用光释放，因此有可能将药物靶向任何活细胞。这项扩大合成细胞功能的基础研究项目具有彻底改变研究领域并带来合成细胞的现实潜力的潜力。

项目成果

Engineering cellular communication between light-activated synthetic cells and bacteria.

• DOI: 10.1038/s41589-023-01374-7
• 发表时间: 2023-09
• 期刊: NATURE CHEMICAL BIOLOGY
• 影响因子: 14.8
• 作者: Smith, Jefferson M.;Hartmann, Denis;Booth, Michael J.
• 通讯作者: Booth, Michael J.