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Research

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{Juritz:2022:10.1063/5.0077865,
author = {Juritz, J and Poulton, JM and Ouldridge, TE},
doi = {10.1063/5.0077865},
journal = {Journal of Chemical Physics},
title = {Minimal mechanism for cyclic templating of length-controlled copolymers under isothermal conditions},
url = {http://dx.doi.org/10.1063/5.0077865},
volume = {156},
year = {2022}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The production of sequence-specific copolymers using copolymer templates is fundamental to the synthesis of complex biological molecules and is a promising framework for the synthesis of synthetic chemical complexes. Unlike the superficially similar process of self-assembly, however, the development of synthetic systems that implement templated copying of copolymers under constant environmental conditions has been challenging. The main difficulty has been overcoming product inhibition or the tendency of products to adhere strongly to their templates—an effect that gets exponentially stronger with the template length. We develop coarse-grained models of copolymerization on a finite-length template and analyze them through stochastic simulation. We use these models first to demonstrate that product inhibition prevents reliable template copying and then ask how this problem can be overcome to achieve cyclic production of polymer copies of the right length and sequence in an autonomous and chemically driven context. We find that a simple addition to the model is sufficient to generate far longer polymer products that initially form on, and then separate from, the template. In this approach, some of the free energy of polymerization is diverted into disrupting copy–template bonds behind the leading edge of the growing copy copolymer. By additionally weakening the final copy–template bond at the end of the template, the model predicts that reliable copying with a high yield of full-length, sequence-matched products is possible over large ranges of parameter space, opening the way to the engineering of synthetic copying systems that operate autonomously.
AU  - Juritz,J
AU  - Poulton,JM
AU  - Ouldridge,TE
DO  - 10.1063/5.0077865
PY  - 2022///
SN  - 0021-9606
TI  - Minimal mechanism for cyclic templating of length-controlled copolymers under isothermal conditions
T2  - Journal of Chemical Physics
UR  - http://dx.doi.org/10.1063/5.0077865
UR  - http://arxiv.org/abs/2111.04164v1
UR  - http://hdl.handle.net/10044/1/94353
VL  - 156
ER  -

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