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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{Sou:2017:10.1002/bit.26456,
author = {Sou, SN and Ken, L and Nayyar, K and Polizzi, KM and Sellick, C and Kontoravdi, C},
doi = {10.1002/bit.26456},
journal = {Biotechnology and Bioengineering},
pages = {512--518},
title = {Exploring cellular behaviour under transient geneexpression and its impact on mAb productivity and Fc glycosylation},
url = {http://dx.doi.org/10.1002/bit.26456},
volume = {115},
year = {2017}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Transient gene expression (TGE) is a methodology employed in bioprocessing for the fast provision of recombinant protein material. Mild hypothermia is often introduced to overcome the low yield typically achieved with TGE and improve specific protein productivity. It is therefore of interest to examine the impact of mild hypothermic temperatures on both the yield and quality of transiently-expressed proteins and the relationship to changes in cellular processes and metabolism. In this study, we focus on the ability of a Chinese hamster ovary cell line to galactosylate a recombinant monoclonal antibody (mAb) product. Through experimentation and flux balance analysis, our results show that TGE in mild hypothermic conditions led to a 76% increase in qP compared to TGE at 36.5°C in our system. This increase is accompanied by increased consumption of nutrients and amino acids, together with increased production of intracellular nucleotide sugar species and higher rates of mAb galactosylation, despite a reduced rate of cell growth. The reduction in biomass accumulation allowed cells to redistribute their energy and resources towards mAb synthesis and Fc-glycosylation. Interestingly, the higher capacity of cells to galactosylate the recombinant product in TGE at 32°C appears not to have been assisted by the upregulation of galactosyltransferases (GalTs), but by the increased expression of N-acetylglucosaminyltransferase II (GnTII) in this cell line, which facilitated the production of bi-antennary glycan structures for further processing.
AU  - Sou,SN
AU  - Ken,L
AU  - Nayyar,K
AU  - Polizzi,KM
AU  - Sellick,C
AU  - Kontoravdi,C
DO  - 10.1002/bit.26456
EP  - 518
PY  - 2017///
SN  - 1097-0290
SP  - 512
TI  - Exploring cellular behaviour under transient geneexpression and its impact on mAb productivity and Fc glycosylation
T2  - Biotechnology and Bioengineering
UR  - http://dx.doi.org/10.1002/bit.26456
UR  - http://hdl.handle.net/10044/1/50815
VL  - 115
ER  -