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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{Perin:2020:10.1101/2020.07.17.206227,
author = {Perin, G and Fletcher, T and Sagi-Kiss, V and Gaboriau, DCA and Carey, MR and Bundy, JG and Jones, PR},
doi = {10.1101/2020.07.17.206227},
title = {Calm on the surface, dynamic on the inside. Molecular homeostasis in response to regulatory and metabolic perturbation of<i>Anabaena</i>sp. PCC 7120 nitrogen metabolism},
url = {http://dx.doi.org/10.1101/2020.07.17.206227},
year = {2020}
}

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RIS format (EndNote, RefMan)

TY - JOUR
AB - <jats:title>Abstract</jats:title><jats:p>Nitrogen is a key macro-nutrient required for the metabolism and growth of biological systems. Although multiple nitrogen sources can serve this purpose, they are all converted into ammonium/ammonia as a first step of assimilation. It is thus reasonable to expect that molecular parts involved in the transport of ammonium/ammonia across biological membranes (i.e. catalysed by AMT transporters) connect with the regulation of both nitrogen and central carbon metabolism. In order to test this hypothesis, we applied both (1) genetic (i.e. Δ<jats:italic>amt</jats:italic>mutation) and (2) environmental treatments to a target biological system, the cyanobacterium Anabaena sp. PCC 7120. Cyanobacteria have a key role in the global nitrogen cycle and thus represent a useful model system. The aim was to both (1) perturb sensing and low-affinity uptake of ammonium/ammonia and (2) induce multiple inner N states, followed by targeted quantification of key proteins, metabolites and enzyme activities, with experiments intentionally designed over a longer time-scale than the available studies in literature. We observed that the absence of AMT transporters triggered a substantial response at a whole-system level, affecting enzyme activities and the quantity of both proteins and metabolites, spanning both N and C metabolism. Moreover, the absence of AMT transporters left a molecular fingerprint indicating N-deficiency even under N replete conditions (i.e. greater GS activity, lower 2-OG content and faster nitrogenase activation upon N deprivation). Contrasting with all of the above dynamic adaptations was the striking near-complete lack of any externally measurable phenotype (i.e. growth, photosynthesis, pigments, metabolites). We thus conclude that this species evolved a highly robust and adaptable molecular network to maintain homeostasis, resulting in substantial internal but minimal external perturbations.
AU - Perin,G
AU - Fletcher,T
AU - Sagi-Kiss,V
AU - Gaboriau,DCA
AU - Carey,MR
AU - Bundy,JG
AU - Jones,PR
DO - 10.1101/2020.07.17.206227
PY - 2020///
TI - Calm on the surface, dynamic on the inside. Molecular homeostasis in response to regulatory and metabolic perturbation of<i>Anabaena</i>sp. PCC 7120 nitrogen metabolism
UR - http://dx.doi.org/10.1101/2020.07.17.206227
ER -

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