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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{Tomazou:2018:10.1016/j.cels.2018.03.013,
author = {Tomazou, M and Barahona, M and Polizzi, K and Stan, G},
doi = {10.1016/j.cels.2018.03.013},
journal = {Cell Systems},
pages = {508--520.e5},
title = {Computational re-design of synthetic genetic oscillators for independent amplitude and frequency modulation},
url = {http://dx.doi.org/10.1016/j.cels.2018.03.013},
volume = {6},
year = {2018}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - To perform well in biotechnology applications, synthetic genetic oscillators must be engineered to allow independent modulation of amplitude and period. This need is currently unmet. Here, we demonstrate computationally how two classic genetic oscillators, the dual-feedback oscillator and the repressilator, can be re-designed to provide independent control of amplitude and period and improve tunability—that is, a broad dynamic range of periods and amplitudes accessible through the input “dials.” Our approach decouples frequency and amplitude modulation by incorporating an orthogonal “sink module” where the key molecular species are channeled for enzymatic degradation. This sink module maintains fast oscillation cycles while alleviating the translational coupling between the oscillator's transcription factors and output. We characterize the behavior of our re-designed oscillators over a broad range of physiologically reasonable parameters, explain why this facilitates broader function and control, and provide general design principles for building synthetic genetic oscillators that are more precisely controllable.
AU  - Tomazou,M
AU  - Barahona,M
AU  - Polizzi,K
AU  - Stan,G
DO  - 10.1016/j.cels.2018.03.013
EP  - 520
PY  - 2018///
SN  - 2405-4712
SP  - 508
TI  - Computational re-design of synthetic genetic oscillators for independent amplitude and frequency modulation
T2  - Cell Systems
UR  - http://dx.doi.org/10.1016/j.cels.2018.03.013
UR  - https://www.cell.com/cell-systems/fulltext/S2405-4712(18)30110-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405471218301108%3Fshowall%3Dtrue
UR  - http://hdl.handle.net/10044/1/56677
VL  - 6
ER  -