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

合成生物学工程生命系统来执行有用的功能。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，即使细胞的遗传信息相同，它们的行为也不尽相同。例如，当我们设计细胞产生特定的分子时，一些细胞有效地产生它，而另一些细胞则不能。这是一个问题，因为低效的电池降低了生产的总体产量。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部发生了什么。然而，这并不是一件容易的事，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零开始制造的人造细胞系统——来观察细胞内部发生的事情。这将有助于我们理解为什么尽管细胞共享相同的遗传信息，但却表现出不同的反应。一种微流控装置将用于生产规模足够大的人造细胞，以分析不同的种群。然后我们将观察单个细胞和它们的反应。结果将用数学模型进行分析，以理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来帮助许多合成生物学应用的商业化。

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.