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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.
@article{Sou:2017:10.1002/bit.26225,
author = {Sou, SN and Jedrzejewski, PM and Lee, K and Sellick, C and Polizzi, KM and Kontoravdi, C},
doi = {10.1002/bit.26225},
journal = {Biotechnology and Bioengineering},
pages = {1570--1582},
title = {Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia},
url = {http://dx.doi.org/10.1002/bit.26225},
volume = {114},
year = {2017}
}
TY - JOUR
AB - Despite the positive effects of mild hypothermic conditions on monoclonal antibody (mAb) productivity (qmAb) during mammalian cell culture, the impact of reduced culture temperature on mAb Fc-glycosylation and the mechanism behind changes in the glycan composition is not fully established. The lack of knowledge about the regulation of dynamic intracellular processes under mild hypothermia restricts bioprocess optimisation. To address this issue, a mathematical model that quantitatively describes CHO cell behaviour and metabolism, mAb synthesis and its N-linked glycosylation profiles before and after the induction of mild hypothermia is constructed using two sets of parameters. Results from this study show that the model is capable of representing experimental results well in all of the aspects mentioned above, including the N-linked glycosylation profile of mAb produced under mild hypothermia. Most importantly, comparison between model simulation results for different culture temperatures suggest the reduced rates of nucleotide sugar donor production and galactosyltransferase (GalT) expression to be critical contributing factors that determine the variation in Fc-glycan profiles between physiological and mild hypothermic conditions in stable CHO transfectants. This is then confirmed using experimental measurements of GalT expression levels, thereby closing the loop between the experimental and the computational system. The identification of bottlenecks within CHO cell metabolism under mild hypothermic conditions will aid bioprocess optimisation, e.g., by tailoring feeding stradegies to improve NSD production, or manipulating the expression of specific glycosyltransferases through cell line engineering.
AU - Sou,SN
AU - Jedrzejewski,PM
AU - Lee,K
AU - Sellick,C
AU - Polizzi,KM
AU - Kontoravdi,C
DO - 10.1002/bit.26225
EP - 1582
PY - 2017///
SN - 1097-0290
SP - 1570
TI - Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia
T2 - Biotechnology and Bioengineering
UR - http://dx.doi.org/10.1002/bit.26225
UR - http://hdl.handle.net/10044/1/42617
VL - 114
ER -