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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{Nikolados:2019:10.1021/acssynbio.8b00531,
author = {Nikolados, E and Weisse, A and Ceroni, F and Oyarzun, D},
doi = {10.1021/acssynbio.8b00531},
journal = {ACS Synthetic Biology},
pages = {1231--1240},
title = {Growth defects and loss-of-function in synthetic gene circuits},
url = {http://dx.doi.org/10.1021/acssynbio.8b00531},
volume = {8},
year = {2019}
}

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RIS format (EndNote, RefMan)

TY - JOUR
AB - Synthetic gene circuits perturb the physiology of their cellular host. The extra load on endogenous processes shifts the equilibrium of resource allocation in the host, leading to slow growth and reduced biosynthesis. Here we built integrated host-circuit models to quantify growth defects caused by synthetic gene circuits. Simulations reveal a complex relation between circuit output and cellular capacity for gene expression. For weak induction of heterologous genes, protein output can be increased at the expense of growth defects. Yet for stronger induction, cellular capacity reaches a tipping point, beyond which both gene expression and growth rate drop sharply. Extensive simulations across various growth conditions and large regions of the design space suggest that the critical capacity is a result of ribosomal scarcity. We studied the impact of growth defects on various gene circuits and transcriptional logic gates, which highlights the extent to which cellular burden can limit, shape, and even break down circuit function. Our approach offers a comprehensive framework to assess the impact of host-circuit interactions in silico, with wide-ranging implications for the design and optimization of bacterial gene circuits.
AU - Nikolados,E
AU - Weisse,A
AU - Ceroni,F
AU - Oyarzun,D
DO - 10.1021/acssynbio.8b00531
EP - 1240
PY - 2019///
SN - 2161-5063
SP - 1231
TI - Growth defects and loss-of-function in synthetic gene circuits
T2 - ACS Synthetic Biology
UR - http://dx.doi.org/10.1021/acssynbio.8b00531
UR - http://hdl.handle.net/10044/1/70931
VL - 8
ER -