Uncovering the basis of cellular self-regeneration

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 what
principles enable sustained regeneration in biochemical, and eventually, biological systems. To
address this, we will:
UKRI BBSRC EASTBIO Doctoral Training Partnership 2022 Cohort: PhD Project Proposal
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1. 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