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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{Jimenez:2016:10.1038/srep28547,
author = {Jimenez, del Val I and Polizzi, K and Kontoravdi, C},
doi = {10.1038/srep28547},
journal = {Scientific Reports},
title = {A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation},
url = {http://dx.doi.org/10.1038/srep28547},
volume = {6},
year = {2016}
}

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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Glycosylation greatly influences the safety and efficacy of many of the highest-selling recombinant therapeutic proteins (rTPs). In order to define optimal cell culture feeding strategies that control rTP glycosylation, it is necessary to know how nucleotide sugars (NSs) are consumed towards host cell and rTP glycosylation. Here, we present a theoretical framework that integrates the reported glycoproteome of CHO cells, the number of N-linked and O-GalNAc glycosylation sites on individual host cell proteins (HCPs), and the carbohydrate content of CHO glycosphingolipids to estimate the demand of NSs towards CHO cell glycosylation. We have identified the most abundant N-linked and O-GalNAc CHO glycoproteins, obtained the weighted frequency of N-linked and O-GalNAc glycosites across the CHO cell proteome, and have derived stoichiometric coefficients for NS consumption towards CHO cell glycosylation. By combining the obtained stoichiometric coefficients with previously reported data for specific growth and productivity of CHO cells, we observe that the demand of NSs towards glycosylation is significant and, thus, is required to better understand the burden of glycosylation on cellular metabolism. The estimated demand of NSs towards CHO cell glycosylation can be used to rationally design feeding strategies that ensure optimal and consistent rTP glycosylation.
AU  - Jimenez,del Val I
AU  - Polizzi,K
AU  - Kontoravdi,C
DO  - 10.1038/srep28547
PY  - 2016///
SN  - 2045-2322
TI  - A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/srep28547
UR  - http://hdl.handle.net/10044/1/33608
VL  - 6
ER  -

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