An engineering rulebook for interfacing living and non-living cells

连接活细胞和非活细胞的工程规则手册

• 批准号: MR/S031537/1
• 负责人: Yuval Elani
• 金额: $ 156.81万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS031537%2F1
• 关键词: engineering; rulebook; interfacing; living; non

Can we reverse engineer living cells and manufacture artificial cells that resemble their biological counterparts from the bottom up? Can these artificial cells be used as micromachines that perform bespoke tasks in physiological environments and as models to gain insights into biological processes? Recent years have seen tremendous advances relating to both these questions, heralding an era of making biology by design. These advances have been made possible by borrowing precision engineering principles long associated with mechanical/electrical devices that helped shape the modern world. Artificial cells have cellular dimensions, incorporate biological machinery (DNA, proteins, lipids, metabolites), and can be designed to possess some of the fundamental features of life. A convergence of technologies has allowed them to be manufactured and manipulated with fine control of the size, morphology, content, compartmentalisation, and function. Artificial cells can now be programmed to swim up concentration gradients, manufacture proteins in response to external stimuli, replicate, and communicate with one another. These accomplishments mean that real-world application of artificial cells - as therapeutic agents, biosensors, self-healing materials, bio/enzymatic reactors - is nearing a reality. In this fellowship, the aim is to go beyond mimicking cells and start using biological cells as integral functional components in a composite system where living and synthetic matter are intermingled - in essence, to use living cells as embedded modules, directly harnessing the power and versatility of biology. Bypassing the limitations associated with making new modules from scratch, and instead hijacking cellular components that have been sculpted through evolution, will enable a step change in artificial cell sophistication and capabilities, and will open up unchartered research areas in biodesign.Over the past three years as an ESPRC Postdoctoral Fellow, I have (i) developed the physical science innovations and technological groundwork that will underpin this endeavour through pioneering advances in microfluidics, optical trapping, and biomembrane engineering that amount to a toolkit for artificial cell construction, and (ii) demonstrated the feasibility of this biohybrid approach through preliminary studies. In this fellowship, building on these advances will achieve full integration between biological and synthetic cells, with the former being used as batteries, sensors, and reactors. Chemically and physically 'wiring up' synthetic and living components will require new technologies to be developed and an engineering rulebook to be devised. Three different hybridisation routes will be explored: (i) Physical hybridisation, where biological and artificial cells are encapsulated within one another to form a unified entity. (ii) Population hybridisation, where biological and artificial cell populations communicate with another through space, exchanging information and material. (iii) Networked hybridisation, where artificial and biological cells are linked through artificial gap junctions in a large-scale tissue-like network.In summary, I will determine how far living and synthetic systems can be fused, and start establishing the foundations of an emerging research area that bridges artificial and living biology. This project is highly ambitious and multi-disciplinary. It covers the physical and life sciences, engineering, and medical spheres. The project relies on industry engagement and includes placements at two industrial partners. It also has a series of leadership objectives, which are of equal importance to the research-focussed ones, and contains a training programme to help me become a scientific leader. For these reasons, the flexible, long-term, and cross-council support offered by the UKRI Future Leaders Fellowship is critical.

我们能否对活细胞进行逆向工程，并制造出自下而上与生物学对应物相似的人造细胞？这些人造细胞能否用作在生理环境中执行定制任务的微型机器，以及作为深入了解生物过程的模型？近年来，在这两个问题上都取得了巨大的进展，预示着一个通过设计制造生物的时代的到来。这些进步是通过借用长期以来与帮助塑造现代世界的机械/电气设备相关的精密工程原理而实现的。人造细胞具有细胞尺寸，包含生物机器（DNA，蛋白质，脂质，代谢物），并且可以被设计为具有生命的一些基本特征。技术的融合使它们能够通过对尺寸、形态、内容、分区和功能的精细控制来制造和操作。人工细胞现在可以被编程为在浓度梯度上游动，响应外部刺激制造蛋白质，复制并相互交流。这些成就意味着人工细胞的现实应用-作为治疗剂，生物传感器，自我修复材料，生物/酶反应器-正在接近现实。在这个奖学金中，目的是超越模仿细胞，并开始使用生物细胞作为复合系统中的完整功能组件，在这个复合系统中，生命和合成物质混合在一起-本质上，使用活细胞作为嵌入式模块，直接利用生物学的力量和多功能性。克服从头开始制造新模块的局限性，并劫持通过进化塑造的细胞组件，将使人工细胞复杂性和能力发生飞跃，并将开辟生物设计领域的未知研究领域。在过去的三年里，作为ESPRC博士后研究员，我已经（i）开发了物理科学创新和技术基础，通过微流体，光学捕获，和生物膜工程，相当于一个工具包的人工细胞建设，和（ii）证明了这种生物杂交方法的可行性，通过初步研究。在这项研究中，基于这些进展，将实现生物和合成细胞之间的完全整合，前者被用作电池，传感器和反应器。化学和物理“布线”合成和生活组件将需要开发新技术和设计工程规则手册。将探索三种不同的杂交途径：（i）物理杂交，其中生物和人工细胞彼此封装以形成统一的实体。(ii)群体杂交，生物和人工细胞群体通过空间相互交流，交换信息和材料。(iii)网络化杂交，人工和生物细胞通过人工间隙连接在一个大规模的组织样网络中连接。总之，我将确定生命和合成系统可以融合到什么程度，并开始建立一个新兴的研究领域的基础，连接人工和生命生物学。这个项目雄心勃勃，涉及多学科。它涵盖了物理和生命科学，工程和医学领域。该项目依赖于行业参与，包括在两个工业合作伙伴的职位。它也有一系列的领导目标，这是同样重要的研究为重点的，并包含一个培训计划，以帮助我成为一个科学的领导者。出于这些原因，UKRI未来领导人奖学金提供的灵活，长期和跨理事会的支持至关重要。

项目成果

What it means to be alive: a synthetic cell perspective

• DOI: 10.1098/rsfs.2023.0036
• 发表时间: 2023-08-11
• 期刊: Interface Focus
• 影响因子: 4.4

Present and future of synthetic cell development

合成细胞开发的现状和未来

• DOI: 10.1038/s41580-023-00686-9
• 发表时间: 2023
• 期刊: Nature Reviews Molecular Cell Biology
• 影响因子: 112.7
• 作者: Adamala K

Layer-by-layer assembly of multi-layered droplet interface bilayers (multi-DIBs).

多层液滴界面双层（multi-DIB）的逐层组装。

• DOI: 10.1039/d1cc05155e
• 发表时间: 2021
• 期刊: Chemical communications (Cambridge, England)
• 作者: Allen ME

Manufacturing polymeric porous capsules.

• DOI: 10.1039/d1cc06565c
• 发表时间: 2022-04-05
• 期刊: Chemical communications (Cambridge, England)
• 作者: Contini C;Hu W;Elani Y
• 通讯作者: Elani Y

Biomimetic behaviors in hydrogel artificial cells through embedded organelles.

水凝胶人造细胞中的仿生行为通过嵌入的细胞器。

• DOI: 10.1073/pnas.2307772120
• 发表时间: 2023-08-29
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Allen, Matthew E.;Hindley, James W.;O'Toole, Nina;Cooke, Hannah S.;Contini, Claudia;Law, Robert, V;Ces, Oscar;Elani, Yuval
• 通讯作者: Elani, Yuval