Uncovering the basis of cellular self-regeneration

自我再生是所有活细胞和生命本身的标志。自下而上的合成生物学和机械建模的最新进展现在为阐明细胞组织如何产生生命系统的这一关键特征提供了强大的工具。体外蛋白质合成系统以前只用于生产外源蛋白质，现在也可以再生自己的成分[1]。至关重要的是，这为确定支持再生的条件开辟了道路。例如，最近的工作表明，在转录和翻译之间平衡分配生化能量是维持再生的关键[1]。然而，支持再生的更一般的“设计原则”仍有待探索。你将结合尖端的无细胞技术[1]和最先进的计算模型[2]，在最大限度控制的环境下研究细胞成分。我们试图回答是什么原则使生化系统以及最终的生物系统能够持续再生。为了解决这个问题，我们将：UKRI BBSRC EASTBIO博士培训伙伴关系2022年队列：博士项目提案21。在微流控下，使用完全定义的无细胞表达系统，测量参与蛋白质合成的关键细胞成分的动力学参数[1]。利用这些数据在[2]的基础上建立无细胞生理学的计算模型，该模型将用于探索和分析持续和适应性自我再生的条件。在模型和实验之间迭代，描述并实验测试自我再生所需的原理和最小组件

Self-regeneration is a hallmark of all living cells and of life itself. Recent advances in bottom-up synthetic biology and mechanistic modelling now offer powerful tools to elucidate how cellular organisation gives rise to this key feature of living systems. In vitro protein synthesis systems, previously only used for exogenous protein production, can now also regenerate its own components [1]. Crucially, this opens up avenues to pinpoint the conditions that support regeneration. For example, recent work showed that a balanced allocation of biochemical energy between transcription and translation is key to sustain regeneration [1]. More general 'design principles' underpinning regeneration, however, still remain unexplored.You will combine cutting-edge cell-free technology [1] and state-of-the-art computational models [2] to study cellular components in a maximally controlled setting. We seek to answer whatprinciples enable sustained regeneration in biochemical, and eventually, biological systems. Toaddress this, we will:UKRI BBSRC EASTBIO Doctoral Training Partnership 2022 Cohort: PhD Project Proposal21. Measure kinetic parameters of key cellular components involved in protein synthesis, using a completely defined cell-free expression system under microfluidic control [1].2. Use the data to build a computational model of cell-free physiology based on [2], which will be used to explore and analyse conditions for sustained and adaptive selfregeneration.3. Characterise and experimentally test principles and minimal components required for self-regeneration, iterating between model and experiment