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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{Plesa:2023:10.1007/s10910-023-01495-3,
author = {Plesa, T and Dack, A and Ouldridge, T},
doi = {10.1007/s10910-023-01495-3},
journal = {Journal of Mathematical Chemistry},
pages = {1980--2018},
title = {Integral feedback in synthetic biology: negative-equilibrium catastrophe},
url = {http://dx.doi.org/10.1007/s10910-023-01495-3},
volume = {61},
year = {2023}
}

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RIS format (EndNote, RefMan)

TY - JOUR
AB - A central goal of synthetic biology is the design of molecular controllers that can manipulate the dynamics of intracellular networks in a stable and accurate manner. To address the factthat detailed knowledge about intracellular networks is unavailable, integral-feedback controllers(IFCs) have been put forward for controlling molecular abundances. These controllers can maintainaccuracy in spite of the uncertainties in the controlled networks. However, this desirable feature isachieved only if stability is also maintained. In this paper, we show that molecular IFCs can sufferfrom a hazardous instability called negative-equilibrium catastrophe (NEC), whereby all nonnegative equilibria vanish under the action of the controllers, and some of the molecular abundancesblow up. We show that unimolecular IFCs do not exist due to a NEC. We then derive a familyof bimolecular IFCs that are safeguarded against NECs when uncertain unimolecular networks,with any number of molecular species, are controlled. However, when IFCs are applied on uncertain bimolecular (and hence most intracellular) networks, we show that preventing NECs generallybecomes an intractable problem as the number of interacting molecular species increases. NECstherefore place a fundamental limit to design and control of molecular networks.
AU - Plesa,T
AU - Dack,A
AU - Ouldridge,T
DO - 10.1007/s10910-023-01495-3
EP - 2018
PY - 2023///
SN - 0259-9791
SP - 1980
TI - Integral feedback in synthetic biology: negative-equilibrium catastrophe
T2 - Journal of Mathematical Chemistry
UR - http://dx.doi.org/10.1007/s10910-023-01495-3
UR - https://link.springer.com/article/10.1007/s10910-023-01495-3
UR - http://hdl.handle.net/10044/1/105397
VL - 61
ER -