Uncovering the basis of cellular self-regeneration

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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