Modelling the Assembly of Artificial Cells into Artificial Organisms

模拟人工细胞组装成人工生物体的过程

• 批准号: RGPIN-2018-04418
• 负责人: Shum, Henry
• 金额: $ 1.53万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=743692
• 关键词: Modelling; Assembly; Artificial; Cells; into

Recent advances in synthetic biology, polymer chemistry, and microfluidics have made the first “artificial cells” a reality. These entities are non-living, micron-sized compartments that allow exchange of certain chemicals with the surrounding environment. Other biomolecules, such as enzymes, encapsulated in the cell enable programmable metabolic pathways to be implemented. It is now timely to explore the possibilities for artificial cells that we can create with the potent tools that are becoming available. The overarching goal of this research program is to guide this exploration by developing theory to model artificial cells, or microrobots, that exhibit collective behaviours and functionality mimicking those of living organisms. One process we are inspired by is morphogenesis, by which nearly all organisms, from bacteria to humans, form distinct structures with distinct purposes. We will construct models describing artificial cells that communicate with each other using chemical signals and spontaneously form “artificial organisms”, where collections of cells of a particular type cluster together in predetermined locations just as tissues and organs develop in biological organisms. To achieve our synthetic version of morphogenesis, two ingredients are needed: (A) mechanisms for directed motility of the cells, and (B) chemical signalling among cells to establish their relative locations. This research program will study biological examples of swimming microorganisms, such as bacteria, to understand and propose suitable mechanisms for achieving controlled motility in relatively simple artificial cells. An emphasis will be placed on locomotion in the presence of solid surfaces. We will also use mathematical modelling to design networks of interacting chemical reactions that coordinate activity throughout the colony of cells. Artificial cells have many uses in medicine; applications as red blood cell substitutes and drug carriers have already received much attention from the scientific community. Advances in designing “smart” artificial cells that can monitor conditions in a patient, travel to specific parts of the body, and coordinate activity would be a significant achievement in minimally invasive healthcare.Investigating the motion of microorganisms near surfaces has implications not only for how to control microrobots or swimming artificial cells, but also how bacteria naturally colonise surfaces, leading to the formation of biofilms. Fouling by biofilms is a dangerous problem on biomedical implants and is also a costly nuisance in many industries, such as shipping, power plants, water treatment plants, and aquaculture. It is anticipated that our research will lead to new strategies for designing biofouling-resistant surfaces.

合成生物学、聚合物化学和微流体学的最新进展使第一批“人造细胞”成为现实。这些实体是无生命的，微米大小的隔间，允许与周围环境交换某些化学物质。其他生物分子，如酶，被封装在细胞中，使可编程的代谢途径得以实现。现在是时候探索人造细胞的可能性了，我们可以用现有的有效工具来创造。这项研究计划的首要目标是通过发展理论来指导这一探索，以模拟人工细胞或微型机器人，它们表现出模仿生物体的集体行为和功能。我们受到形态发生过程的启发，几乎所有的生物，从细菌到人类，都形成了具有不同目的的不同结构。我们将构建描述人工细胞的模型，这些细胞利用化学信号相互交流，并自发形成“人工有机体”，在这种有机体中，特定类型的细胞集合在预定的位置聚集在一起，就像生物有机体中的组织和器官发育一样。为了实现我们的合成形态发生，需要两个要素：(A)细胞定向运动的机制，(B)细胞之间的化学信号传导，以确定它们的相对位置。该研究项目将研究游动微生物（如细菌）的生物学例子，以了解并提出在相对简单的人造细胞中实现受控运动的合适机制。重点将放在有固体表面时的运动。我们还将使用数学模型来设计相互作用的化学反应网络，以协调整个细胞群的活动。人造细胞在医学上有许多用途；作为红细胞替代品和药物载体的应用已经受到了科学界的广泛关注。在设计“智能”人造细胞方面的进展，可以监测病人的状况，移动到身体的特定部位，并协调活动，这将是微创医疗领域的一项重大成就。研究微生物在表面附近的运动不仅对如何控制微型机器人或游动的人造细胞有意义，而且对细菌如何自然地在表面上定植，导致生物膜的形成也有意义。生物膜污染是生物医学植入物的一个危险问题，在许多行业，如航运、发电厂、水处理厂和水产养殖业，也是一个代价高昂的麻烦。预计我们的研究将导致设计抗生物污染表面的新策略。