In this section

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{Schaerli:2018:10.15252/msb.20178102,
author = {Schaerli, Y and Jiménez, A and Duarte, JM and Mihajlovic, L and Renggli, J and Isalan, M and Sharpe, J and Wagner, A},
doi = {10.15252/msb.20178102},
journal = {Molecular Systems Biology},
title = {Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution},
url = {http://dx.doi.org/10.15252/msb.20178102},
volume = {14},
year = {2018}
}

Download

RIS format (EndNote, RefMan)

TY - JOUR
AB - Phenotypic variation is the raw material of adaptive Darwinian evolution. The phenotypic variation found in organismal development is biased towards certain phenotypes, but the molecular mechanisms behind such biases are still poorly understood. Gene regulatory networks have been proposed as one cause of constrained phenotypic variation. However, most pertinent evidence is theoretical rather than experimental. Here, we study evolutionary biases in two synthetic gene regulatory circuits expressed in Escherichia coli that produce a gene expression stripe—a pivotal pattern in embryonic development. The two parental circuits produce the same phenotype, but create it through different regulatory mechanisms. We show that mutations cause distinct novel phenotypes in the two networks and use a combination of experimental measurements, mathematical modelling and DNA sequencing to understand why mutations bring forth only some but not other novel gene expression phenotypes. Our results reveal that the regulatory mechanisms of networks restrict the possible phenotypic variation upon mutation. Consequently, seemingly equivalent networks can indeed be distinct in how they constrain the outcome of further evolution.
AU - Schaerli,Y
AU - Jiménez,A
AU - Duarte,JM
AU - Mihajlovic,L
AU - Renggli,J
AU - Isalan,M
AU - Sharpe,J
AU - Wagner,A
DO - 10.15252/msb.20178102
PY - 2018///
SN - 1744-4292
TI - Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution
T2 - Molecular Systems Biology
UR - http://dx.doi.org/10.15252/msb.20178102
UR - http://hdl.handle.net/10044/1/63525
VL - 14
ER -