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Nucleic Acid Nanotechnology Originated ProtoCell - NANOPC

源于ProtoCell的核酸纳米技术 - NANOPC

基本信息

批准号：
EP/X023303/1
负责人：
Wooli Bae
金额：
$ 44.58万
依托单位：
University of Surrey
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：
未结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FX023303%2F1
关键词：
Nucleic Acid Nanotechnology Originated ProtoCell

项目摘要

Cells, the basic units of life, are dynamic systems that sense the environment and adapt to it through a variety of responses. Understanding and engineering living cells, although highly rewarding, is greatly challenging, due to the complexity of biochemical networks that underlie a cell's most sophisticated functions. A simpler synthetic alternative to real cells - protocells - can therefore be built to design systems with cell-like traits. Protocells promise to facilitate our understanding of the principles of biology, and could, have important medical and engineering implications. Despite recent progress, current protocell systems fail to mimic core operating principles of cells to continuously operate, interact with the external environment, and process information to make decisions. Here, we will develop a Nucleic Acid Nanotechnology Originated ProtoCell (NANOPC) system using rationally designed DNA and RNA components. State-of-the-art DNA/RNA nanotechnology will be used to build nanostructures and reaction circuits that mimic proteins and genetic networks of a cell with unprecedented precision. Reaction circuits made of DNA and RNA are fully programmable and can be easily combined to each other, which will allow us in the long run, to build complex multifunctional protocells on demand. In addition, the NANOPC will continuously operate these reaction circuits at dynamic equilibrium by using my recent achievement to produce RNA components in situ. The reaction circuits will be used to control the uptake of nutrients from the external environment, implementing sensing-mediated controls for example, in feedback loops. By programming NA nanostructures and reaction circuits, the NANOPC will be able to implement emergent cellular behaviours such as the ability to maintain its internal stability (homeostasis) and processing information. Therefore, the NANOPC will be a novel platform to study basic principles of biology. The versatility of DNA/RNA nanotechnology will ultimately enable NANOPC to generate biomedical and engineering applications. For example, the NANOPC could be a high throughput platform for prototyping biochemical networks or a smart drug delivery system to sense tumour microenvironment, process multiple information to release drugs.

细胞是生命的基本单位，是感知环境并通过各种反应适应环境的动态系统。尽管理解和设计活细胞是非常有意义的，但由于作为细胞最复杂功能基础的生化网络的复杂性，活细胞的设计是非常具有挑战性的。因此，可以建造一种比真实细胞更简单的合成替代品--原细胞--来设计具有细胞样特征的系统。原细胞有望促进我们对生物学原理的理解，并可能具有重要的医学和工程学意义。尽管最近取得了进展，但目前的原细胞系统未能模仿细胞的核心工作原理来持续运行，与外部环境相互作用，并处理信息以做出决定。在这里，我们将开发一个使用合理设计的DNA和RNA组件的核酸纳米技术起源的原始细胞(NANOPC)系统。最先进的DNA/RNA纳米技术将被用来构建纳米结构和反应电路，以前所未有的精度模拟细胞的蛋白质和遗传网络。由DNA和RNA组成的反应电路是完全可编程的，可以很容易地相互结合，从长远来看，这将使我们能够根据需要建造复杂的多功能原始细胞。此外，NANOPC将利用我最近的成果在原位生产RNA组分，使这些反应电路持续处于动态平衡状态。反应回路将被用来控制从外部环境中摄取营养物质，例如在反馈回路中实施感知中介控制。通过对NA纳米结构和反应电路进行编程，NANOPC将能够实现紧急的细胞行为，例如维持其内部稳定(动态平衡)和处理信息的能力。因此，NANOPC将成为一个研究生物学基本原理的新平台。DNA/RNA纳米技术的多功能性最终将使NANOPC产生生物医学和工程应用。例如，NANOPC可以是一个高通量的生化网络原型平台，或者是一个感知肿瘤微环境、处理多种信息以释放药物的智能药物输送系统。