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{Berengut:2020:10.1021/acsnano.0c07696,
author = {Berengut, J and Kui, Wong C and Berengut, J and Doye, J and Ouldridge, T and Lee, L},
doi = {10.1021/acsnano.0c07696},
journal = {ACS Nano},
pages = {17428--17441},
title = {Self-limiting polymerization of DNA origami  subunits with strain accumulation},
url = {http://dx.doi.org/10.1021/acsnano.0c07696},
volume = {14},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Biology demonstrates how a near infinite array of complex systems and structures at many scales can originate from the self-assembly of component parts on the nanoscale. But to fully exploit the benefits of self-assembly for nanotechnology, a crucial challenge remains: How do we rationally encode well-defined global architectures in subunits that are much smaller than their assemblies? Strain accumulation via geometric frustration is one mechanism that has been used to explain the self-assembly of global architectures in diverse and complex systems a posteriori. Here we take the next step and use strain accumulation as a rational design principle to control the length distributions of self-assembling polymers. We use the DNA origami method to design and synthesize a molecular subunit known as the PolyBrick, which perturbs its shape in response to local interactions via flexible allosteric blocking domains. These perturbations accumulate at the ends of polymers during growth, until the deformation becomes incompatible with further extension. We demonstrate that the key thermodynamic factors for controlling length distributions are the intersubunit binding free energy and the fundamental strain free energy, both which can be rationally encoded in a PolyBrick subunit. While passive polymerization yields geometrical distributions, which have the highest statistical length uncertainty for a given mean, the PolyBrick yields polymers that approach Gaussian length distributions whose variance is entirely determined by the strain free energy. We also show how strain accumulation can in principle yield length distributions that become tighter with increasing subunit affinity and approach distributions with uniform polymer lengths. Finally, coarse-grained molecular dynamics and Monte Carlo simulations delineate and quantify the dominant forces influencing strain accumulation in a molecular system. This study constitutes a fundamental investigation of the use of strain accumula
AU  - Berengut,J
AU  - Kui,Wong C
AU  - Berengut,J
AU  - Doye,J
AU  - Ouldridge,T
AU  - Lee,L
DO  - 10.1021/acsnano.0c07696
EP  - 17441
PY  - 2020///
SN  - 1936-0851
SP  - 17428
TI  - Self-limiting polymerization of DNA origami  subunits with strain accumulation
T2  - ACS Nano
UR  - http://dx.doi.org/10.1021/acsnano.0c07696
UR  - http://hdl.handle.net/10044/1/85773
VL  - 14
ER  -
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