Research

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Synthetic Biology underpins advances in the bioeconomy

Biological systems - including the simplest cells - exhibit a broad range of functions to thrive in their environment. Research in the Imperial College Centre for Synthetic Biology is focused on the possibility of engineering the underlying biochemical processes to solve many of the challenges facing society, from healthcare to sustainable energy. In particular, we model, analyse, design and build biological and biochemical systems in living cells and/or in cell extracts, both exploring and enhancing the engineering potential of biology. 

As part of our research we develop novel methods to accelerate the celebrated Design-Build-Test-Learn synthetic biology cycle. As such research in the Centre for Synthetic Biology highly multi- and interdisciplinary covering computational modelling and machine learning approaches; automated platform development and genetic circuit engineering ; multi-cellular and multi-organismal interactions, including gene drive and genome engineering; metabolic engineering; in vitro/cell-free synthetic biology; engineered phages and directed evolution; and biomimetics, biomaterials and biological engineering.

Publications

Citation

BibTex format

@article{Poulton:2021:1367-2630/ac0389,
author = {Poulton, JM and Ouldridge, TE},
doi = {1367-2630/ac0389},
journal = {New Journal of Physics},
pages = {1--14},
title = {Edge-effects dominate copying thermodynamics for finite-length molecular  oligomers},
url = {http://dx.doi.org/10.1088/1367-2630/ac0389},
volume = {23},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - A signature feature of living systems is their ability to produce copies ofinformation-carrying molecular templates such as DNA. These copies are madeby assembling a set of monomer molecules into a linear macromolecule with a sequence determined by the template. The copies produced have a finite length –they are often “oligomers”, or short polymers – and must eventually detach fromtheir template. We explore the role of the resultant initiation and termination ofthe copy process in the thermodynamics of copying. By splitting the free-energychange of copy formation into informational and chemical terms, we show that,surprisingly, copy accuracy plays no direct role in the overall thermodynamics. Instead, finite-length templates function as highly-selective engines that interconvertchemical and information-based free energy stored in the environment; it is thermodynamically costly to produce outputs that are more similar to the oligomersin the environment than sequences obtained by randomly sampling monomers. Incontrast to previous work that neglects separation, any excess free energy stored incorrelations between copy and template sequences is lost when the copy fully detaches and mixes with the environment; these correlations therefore do not featurein the overall thermodynamics. Previously-derived constraints on copy accuracytherefore only manifest as kinetic barriers experienced while the copy is templateattached; these barriers are easily surmounted by shorter oligomers.
AU  - Poulton,JM
AU  - Ouldridge,TE
DO  - 1367-2630/ac0389
EP  - 14
PY  - 2021///
SN  - 1367-2630
SP  - 1
TI  - Edge-effects dominate copying thermodynamics for finite-length molecular  oligomers
T2  - New Journal of Physics
UR  - http://dx.doi.org/10.1088/1367-2630/ac0389
UR  - http://arxiv.org/abs/2005.11255v2
UR  - https://iopscience.iop.org/article/10.1088/1367-2630/ac0389
UR  - http://hdl.handle.net/10044/1/88816
VL  - 23
ER  -
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