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

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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.