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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{Frei:2020:10.1038/s41467-020-18392-x,
author = {Frei, T and Cella, F and Tedeschi, F and Gutiérrez, J and Stan, G-B and Khammash, M and Siciliano, V},
doi = {10.1038/s41467-020-18392-x},
journal = {Nature Communications},
title = {Characterization and mitigation of gene expression burden in mammalian cells},
url = {http://dx.doi.org/10.1038/s41467-020-18392-x},
volume = {11},
year = {2020}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Despite recent advances in circuit engineering, the design of genetic networks in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here, we demonstrate that transiently expressed genes in mammalian cells compete for limited transcriptional and translational resources. This competition results in the coupling of otherwise independent exogenous and endogenous genes, creating a divergence between intended and actual function. Guided by a resource-aware mathematical model, we identify and engineer natural and synthetic miRNA-based incoherent feedforward loop (iFFL) circuits that mitigate gene expression burden. The implementation of these circuits features the use of endogenous miRNAs as elementary components of the engineered iFFL device, a versatile hybrid design that allows burden mitigation to be achieved across different cell-lines with minimal resource requirements. This study establishes the foundations for context-aware prediction and improvement of in vivo synthetic circuit performance, paving the way towards more rational synthetic construct design in mammalian cells.
AU  - Frei,T
AU  - Cella,F
AU  - Tedeschi,F
AU  - Gutiérrez,J
AU  - Stan,G-B
AU  - Khammash,M
AU  - Siciliano,V
DO  - 10.1038/s41467-020-18392-x
PY  - 2020///
SN  - 2041-1723
TI  - Characterization and mitigation of gene expression burden in mammalian cells
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-020-18392-x
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32934213
UR  - http://hdl.handle.net/10044/1/83938
VL  - 11
ER  -