Japan_IPAP: High-Throughput Prototyping of Heterogeneity in genetic networks using Artificial Cells with femtolitre volume (HT-PHAC)

Japan_IPAP：使用飞升体积的人工细胞（HT-PHAC）对遗传网络中的异质性进行高通量原型设计

• 批准号: BB/X01262X/1
• 负责人: Wooli Bae
• 金额: $ 19.35万
• 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=BB%2FX01262X%2F1
• 关键词: Japan_IPAP; Throughput; Prototyping; Heterogeneity; genetic

Synthetic biology engineers living systems to perform useful functions. For example, we engineer small bacteria's genomes to produce expensive vitamins or to degrade plastic waste. However, cells do not behave the same even when their genetic information is the same. For example, when we engineer cells to produce a specific molecule, some cells produce it efficiently while other cells do not. This is a problem because the overall yield of production is reduced because of inefficient cells. This increase in the production cost is one of the major obstacles that need to be overcome to commercialise many synthetic biology applications. To solve this problem, we need to know what is happening inside each cell. However, it is not an easy task because a cell is a complex object. Even a simple bacterial cell has more than one million molecules inside its cytoplasm. In this proposal, we will develop a simple cell mimic - an artificial cell system made from scratch using synthetic elements - to observe what is happening inside a cell. This will help us to understand why cells show different responses despite sharing the same genetic information. A microfluidic device will be used to produce artificial cells at a scale large enough to analyse different populations. Then we will observe individual cells and their responses. The result will be analysed with mathematical modelling to understand why certain cells behave differently from other cells. This knowledge will allow us to engineer cells that exhibit homogeneous and consistent behaviour. In a long term, this work will help commercialise a lot of synthetic biology applications by reducing their production costs.

合成生物学让生命系统发挥有用的功能。例如，我们改造小细菌的基因组来生产昂贵的维生素或降解塑料垃圾。然而，细胞的行为并不相同，即使它们的遗传信息是相同的。例如，当我们设计细胞来产生特定的分子时，一些细胞高效地制造它，而另一些细胞则不能。这是一个问题，因为由于电池效率低下，生产的总体产量降低了。生产成本的增加是许多合成生物学应用商业化需要克服的主要障碍之一。要解决这个问题，我们需要知道每个细胞内部发生了什么。然而，这并不是一项容易的任务，因为单元格是一个复杂的对象。即使是一个简单的细菌细胞，其细胞质中也有100多万个分子。在这项提案中，我们将开发一种简单的细胞模拟--一种使用合成元素从头开始制作的人造细胞系统--来观察细胞内发生的事情。这将帮助我们理解为什么细胞在共享相同的基因信息时表现出不同的反应。一种微流控设备将被用来生产规模足够大的人造细胞，以分析不同的人群。然后我们将观察单个细胞及其反应。结果将通过数学建模进行分析，以了解为什么某些细胞的行为与其他细胞不同。这一知识将使我们能够设计出表现出同质和一致行为的细胞。从长远来看，这项工作将通过降低生产成本，帮助将大量合成生物学应用商业化。