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

合成生物学工程师生命系统执行有用的功能。例如，我们设计小细菌的基因组来生产昂贵的维生素或降解塑料废物。然而，即使它们的遗传信息相同，细胞的行为也不相同。例如，当我们设计细胞以产生特定分子时，一些细胞有效地产生它，而其他细胞则不能。这是一个问题，因为生产的总产量由于低效的电池而降低。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。为了解决这个问题，我们需要知道每个细胞内发生了什么。然而，这并不是一件容易的事情，因为细胞是一个复杂的对象。即使是一个简单的细菌细胞，其细胞质中也有超过一百万个分子。在这个提议中，我们将开发一个简单的细胞模拟物--一个使用合成元素从头开始制造的人工细胞系统--来观察细胞内发生的事情。这将有助于我们理解为什么细胞在共享相同遗传信息的情况下会显示出不同的反应。微流控装置将用于生产人工细胞，其规模足以分析不同的群体。然后我们将观察单个细胞及其反应。研究人员将通过数学建模来分析结果，以了解为什么某些细胞的行为与其他细胞不同。这些知识将使我们能够设计出表现出均匀和一致行为的细胞。从长远来看，这项工作将通过降低生产成本来帮助许多合成生物学应用商业化。

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.