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Synthetic Biology underpins advances in the bioeconomy

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.

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  • Journal article
    Ferdous Z, Fuchs S, Behrends V, Trasanidis N, Vlachou D, Christophides GKet al.,

    Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding

    <jats:title>Abstract</jats:title><jats:p>Vitellogenesis and oocyte maturation require anautogenous female <jats:italic>Anopheles</jats:italic> mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito <jats:italic>Anopheles coluzzii</jats:italic>. We show that RNA interference (RNAi) silencing of <jats:italic>SCD1</jats:italic> and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by <jats:italic>SCD1</jats:italic> knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the <jats:italic>SCD1</jats:italic> KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune respo

  • Journal article
    Poulton JM, Ouldridge TE,

    Edge-effects dominate copying thermodynamics for finite-length molecular oligomers

    Living systems produce copies of information-carrying molecules such as DNAby assembling monomer units into finite-length oligomer (short polymer) copies.We explore the role of initiation and termination of the copy process in thethermodynamics of copying. By splitting the free-energy change of copyformation into informational and chemical terms, we show that copy accuracyplays no direct role in the overall thermodynamics. Instead, it isthermodynamically costly to produce outputs that are more similar to theoligomers in the environment than sequences obtained by randomly samplingmonomers. Copy accuracy can be thermodynamically neutral, or even favoured,depending on the surroundings. Oligomer copying mechanisms can thus function asinformation engines that interconvert chemical and information-based freeenergy. Hard thermodynamic constraints on accuracy derived for infinite-lengthpolymers instead manifest as kinetic barriers experienced while the copy istemplate-attached. These barriers are easily surmounted by shorter oligomers.

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