Effects of the spatial distribution of resources on the performance of genetic circuits

资源空间分布对遗传回路性能的影响

• 批准号: 2898865
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 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=studentship-2898865
• 关键词: Effects; spatial; distribution; resources; performance

The availability of transcriptional and translational resources plays an important role in gene expression and is a key factor affecting the performance of synthetic genetic circuits and metabolic pathways. While there are extensive investigations of trade-offs between growth, cellular capacity for gene expression and allocation of cellular resources, little is known about how the spatial distribution of these resources impacts gene expression. Contrary to common assumptions, even simple cells lacking organelles like bacteria are heterogenous and far from well-mixed vessels where biochemical reactions take place. In particular, it has been demonstrated that well-characterised microorganisms such as Escherichia coli have a non-homogenous distribution of the transcriptional and translational machinery.In this project we will investigate how the cytoplasmic location of the genes and the resources required for expression affect the performance of genetic circuits. Some pioneering works show that the distance between genes composing the same circuit influences their dynamic behaviour given that molecules such as transcriptional regulators need to diffuse to different regions of the cell2. Likewise, non-homogeneously distributed ribosomes and RNA polymerases need to diffuse to the locations of the cell at which the relevant mRNAs and proteins are produced. We hypothesise that the 'local' demand for resources plays a role in determining the final expression levels of genes of interest. Considering space as a design variable is, therefore, a novel aspect of synthetic biology that we will assess in this project.

转录和翻译资源的可用性在基因表达中起着重要作用，并且是影响合成遗传回路和代谢途径性能的关键因素。尽管对生长，基因表达的细胞能力和细胞资源的分配之间的权衡进行了广泛的研究，但对于这些资源的空间分布如何影响基因表达，知之甚少。与常见的假设相反，即使是缺乏细菌等细胞器的简单细胞也是异质的，并且远非发生生化反应的混合良好血管。特别是，已经证明，诸如大肠杆菌等特征良好的微生物具有转录和翻译机械的非基础分布。在该项目中，我们将研究基因的细胞质位置以及表达表达所需的细胞质位置如何影响遗传回路的性能。一些开创性的作品表明，构成相同电路的基因之间的距离会影响其动态行为，因为分子（例如转录调节剂）需要扩散到细胞2的不同区域。同样，非均匀分布的核糖体和RNA聚合酶需要扩散到产生相关mRNA和蛋白质的细胞位置。我们假设对资源的“本地”需求在确定感兴趣基因的最终表达水平中起着作用。因此，将空间视为设计变量是我们将在该项目中评估的合成生物学的新方面。