Imperial College London

Dr Cleo Kontoravdi

Faculty of EngineeringDepartment of Chemical Engineering

Reader in Biosystems Engineering
 
 
 
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Contact

 

+44 (0)20 7594 6655cleo.kontoravdi98 Website

 
 
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Location

 

516ACE ExtensionSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
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64 results found

Cardenas-Fernandez M, Bawn M, Hamley-Bennett C, Bharat PKV, Subrizi F, Suhaili N, Ward DP, Bourdin S, Dalby PA, Hailes HC, Hewitson P, Ignatova S, Kontoravdi C, Leak DJ, Shah N, Sheppard TD, Ward JM, Lye GJet al., 2017, An integrated biorefinery concept for conversion of sugar beet pulp into value-added chemicals and pharmaceutical intermediates, FARADAY DISCUSSIONS, Vol: 202, Pages: 415-431, ISSN: 1359-6640

JOURNAL ARTICLE

Goers L, Ainsworth C, Goey CH, Kontoravdi C, Freemont PS, Polizzi KMet al., 2017, Whole-cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 114, Pages: 1290-1300, ISSN: 0006-3592

JOURNAL ARTICLE

Goers L, Ainsworth C, Goey CH, Kontoravdi C, Freemont PS, Polizzi KMet al., 2017, Cover Image, Volume 114, Number 6, June 2017., Biotechnol Bioeng, Vol: 114

Cover Legend The cover image, by Lisa Goers et al., is based on the Article Whole-cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production, DOI: 10.1002/bit.26254.

JOURNAL ARTICLE

Goey CH, Tsang JMH, Bell D, Kontoravdi Cet al., 2017, Cascading effect in bioprocessing-The impact of mild hypothermia on CHO cell behavior and host cell protein composition., Biotechnol Bioeng

A major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture conditions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the HCP profile. We examined how temperature downshift (TDS) to mild hypothermia affects key upstream performance indicators, that is antibody titre, HCP concentration and HCP species, across the cell culture decline phase and at harvest through the lens of changes in cellular behavior. Mild hypothermic conditions introduced on day 5 of fed-batch Chinese hamster ovary (CHO) cell bioreactors resulted in a lower cell proliferation rate but larger percentages of healthier cells across the cell culture decline phase compared to bioreactors maintained at standard physiological temperature. Moreover, the onset of apoptosis was less evident in mild hypothermic cultures. Consequently, mild hypothermic cultures took an extra 5 days to reach an integral viable cell concentration (IVCC) and antibody yield similar to that of the control at standard physiological temperature. When cell viability dropped below 80%, mild hypothermic cell cultures had a reduced variety of HCP species by 36%, including approximately 44% and 27% lower proteases and chaperones, respectively, despite having similar HCP concentration. This study suggests that TDS may be a good strategy to provide cleaner downstream feedstocks by reducing the variety of HCPs and to maintain product integrity by reducing the number of proteases and chaperones.

JOURNAL ARTICLE

Sou SN, Jedrzejewski PM, Lee K, Sellick C, Polizzi KM, Kontoravdi Cet al., 2017, Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 114, Pages: 1570-1582, ISSN: 0006-3592

JOURNAL ARTICLE

Sou SN, Lee K, Nayyar K, Polizzi KM, Sellick C, Kontoravdi Cet al., 2017, Exploring cellular behaviour under transient gene expression and its impact on mAb productivity and Fc-glycosylation., Biotechnol Bioeng

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. This article is protected by copyright. All rights reserved.

JOURNAL ARTICLE

Klymenko OV, Shah N, Kontoravdi C, Royle KE, Polizzi KMet al., 2016, Designing an Artificial Golgi Reactor to Achieve Targeted Glycosylation of Monoclonal Antibodies, AICHE JOURNAL, Vol: 62, Pages: 2959-2973, ISSN: 0001-1541

JOURNAL ARTICLE

Niu H, Shah N, Kontoravdi C, 2016, Modelling of amorphous cellulose depolymerisation by cellulases, parametric studies and optimisation, BIOCHEMICAL ENGINEERING JOURNAL, Vol: 105, Pages: 455-472, ISSN: 1369-703X

JOURNAL ARTICLE

del Val IJ, Polizzi KM, Kontoravdi C, 2016, A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322

JOURNAL ARTICLE

Fan Y, Del Val IJ, Mueller C, Sen JW, Rasmussen SK, Kontoravdi C, Weilguny D, Andersen MRet al., 2015, Amino Acid and Glucose Metabolism in Fed-Batch CHO Cell Culture Affects Antibody Production and Glycosylation, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 521-535, ISSN: 0006-3592

JOURNAL ARTICLE

Fan Y, Del Val IJ, Muller C, Lund AM, Sen JW, Rasmussen SK, Kontoravdi C, Baycin-Hizal D, Betenbaugh MJ, Weilguny D, Andersen MRet al., 2015, A multi-pronged investigation into the effect of glucose starvation and culture duration on fed-batch CHO cell culture, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 2172-2184, ISSN: 0006-3592

JOURNAL ARTICLE

Niv H, Leak D, Shah N, Kontoravdi Cet al., 2015, Metabolic characterization and modeling of fermentation process of an engineered Geobacillus thermoglucosidasius strain for bioethanol production with gas stripping, CHEMICAL ENGINEERING SCIENCE, Vol: 122, Pages: 138-149, ISSN: 0009-2509

JOURNAL ARTICLE

Oliveira PH, Mairhofer J, Alves PM, Lara AR, Kontoravdi Cet al., 2015, Advances in the Development of Biotherapeutics, BioMed Research International, Vol: 2015, ISSN: 2314-6133

JOURNAL ARTICLE

Polizzi KM, Kontoravdi C, 2015, Genetically-encoded biosensors for monitoring cellular stress in bioprocessing, CURRENT OPINION IN BIOTECHNOLOGY, Vol: 31, Pages: 50-56, ISSN: 0958-1669

JOURNAL ARTICLE

Sou SN, Sellick C, Lee K, Mason A, Kyriakopoulos S, Polizzi KM, Kontoravdi Cet al., 2015, How does mild hypothermia affect monoclonal antibody glycosylation?, Biotechnology and Bioengineering, Vol: 112, Pages: 1165-1176, ISSN: 1097-0290

JOURNAL ARTICLE

Behjousiar A, Constantinou A, Polizzi KM, Kontoravdi Cet al., 2014, FIBS-enabled Noninvasive Metabolic Profiling, Jove-Journal of Visualized Experiments, ISSN: 1940-087X

JOURNAL ARTICLE

Jedrzejewski PM, del Val IJ, Constantinou A, Dell A, Haslam SM, Polizzi KM, Kontoravdi Cet al., 2014, Towards Controlling the Glycoform: A Model Framework Linking Extracellular Metabolites to Antibody Glycosylation, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 15, Pages: 4492-4522, ISSN: 1422-0067

JOURNAL ARTICLE

Kyriakopoulos S, Kontoravdi C, 2014, A Framework for the Systematic Design of Fed-Batch Strategies in Mammalian Cell Culture, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 111, Pages: 2466-2476, ISSN: 0006-3592

JOURNAL ARTICLE

Kyriakopoulos S, Kontoravdi C, 2014, Insights on biomarkers from Chinese hamster ovary ‘omics’ studies, Pharmaceutical Bioprocessing, Vol: 2, Pages: 389-401, ISSN: 2048-9145

JOURNAL ARTICLE

Todri E, Amenaghawon AN, del Val IJ, Leak DJ, Kontoravdi C, Kucherenko S, Shah Net al., 2014, Global sensitivity analysis and meta-modeling of an ethanol production process, CHEMICAL ENGINEERING SCIENCE, Vol: 114, Pages: 114-127, ISSN: 0009-2509

JOURNAL ARTICLE

Chen N, Bennett MH, Kontoravdi C, 2013, Analysis of Chinese hamster ovary cell metabolism through a combined computational and experimental approach, Cytotechnology, Vol: Online First

JOURNAL ARTICLE

Jedrzejewski PM, Jimenez del Val I, Polizzi KM, Kontoravdi Cet al., 2013, Applying quality by design to glycoprotein therapeutics: experimental and computational efforts of process control, Pharmaceutical Bioprocessing, Vol: 1, Pages: 51-69

JOURNAL ARTICLE

Jimenez Del Val I, Constantinou A, Dell A, Haslam S, Jedrzejewski P, Polizzi KM, Kontoravdi Cet al., 2013, An integrated mechanistic model for nucleotide sugar metabolism and monoclonal antibody glycosylation, Pages: 658-659

CONFERENCE PAPER

Jimenez del Val I, Constantinou A, Dell A, Haslam S, Polizzi KM, Kontoravdi Cet al., 2013, A quantitative and mechanistic model for monoclonal antibody glycosylation as a function of nutrient availability during cell culture, 23rd European Society for Animal Cell Technology (ESACT) Meeting: Better Cells for Better Health

CONFERENCE PAPER

Kontoravdi C, 2013, Systematic methodology for the development of mathematical models for biological processes., Methods Mol Biol, Vol: 1073, Pages: 177-190

Synthetic biology gives researchers the opportunity to rationally (re-)design cellular activities to achieve a desired function. The design of networks of pathways towards accomplishing this calls for the application of engineering principles, often using model-based tools. Success heavily depends on model reliability. Herein, we present a systematic methodology for developing predictive models comprising model formulation considerations, global sensitivity analysis, model reduction (for highly complex models or where experimental data are limited), optimal experimental design for parameter estimation, and predictive capability checking. Its efficacy and validity are demonstrated using an example from bioprocessing. This approach systematizes the process of developing reliable mathematical models at a minimum experimental cost, enabling in silico simulation and optimization.

JOURNAL ARTICLE

Kontoravdi C, Samsatli NJ, Shah N, 2013, Development and design of bio-pharmaceutical processes, CURRENT OPINION IN CHEMICAL ENGINEERING, Vol: 2, Pages: 435-441, ISSN: 2211-3398

JOURNAL ARTICLE

Kyriakopoulos S, Polizzi KM, Kontoravdi C, 2013, Comparative analysis of amino acid metabolism and transport in CHO variants with different levels of productivity, JOURNAL OF BIOTECHNOLOGY, Vol: 168, Pages: 543-551, ISSN: 0168-1656

JOURNAL ARTICLE

Kyriakopoulos S, Polizzi KM, Kontoravdi C, 2013, Dynamic profiling of amino acid transport and metabolism in Chinese hamster ovary cell culture., Pages: P97-P97, ISSN: 1753-6561

CONFERENCE PAPER

Polizzi KM, Hallett JP, Kontoravdi C, Shah Net al., 2013, Frontier manufacturing: Scaling up synthetic biology

CONFERENCE PAPER

Royle K, Jimenez Del Val I, Miller A, Polizzi KM, Kontoravdi Cet al., 2013, Designing a synthetic Golgi reactor, Pages: 341-342

CONFERENCE PAPER

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