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

 

Overview

My interests lie in the area of biotechnology with particular focus on the application of systems engineering principles to bioprocessing. The group's research involves the systematic integration of model-based tools, such as sensitivity analysis, design of experiments and optimisation, with experimentation on mammalian cell culture systems with a focus on metabolism and protein quality.

GC

 

Furthermore, our group is working towards establishing more robust processes for cell line selection and culture operation. I also work closely with Dr. Karen Polizzi (Department of Life Sciences) in the area of neurodegeneration, in particular on Alzheimer's disease.

I am a member of the Centre for Process Systems Engineering.

Current research projects include:

frontier manufacturing: scaling-up synthetic biology


In collaboration with Dr Karen Polizzi, Dr Francesca Ceroni, Prof. Jason Hallett and Prof Nilay Shah

Postdoctoral Researchers: Drs Ignacio Moya Ramirez, Gizem Buldum, Vaishali Thaore and Dimitra Gialama

PhD students: Ms Chiara Heide and Ms Elli Makrydaki

Synthetic biology has the potential to revolutionise the way we make a host of consumer products from materials and energy to food and medicine. In order for this impact to be realised, we must find the best way to translate laboratory discoveries into operating industrial production processes. The challenge here is to transition from existing factories into the factories of the future.

In this part of the project, we are focusing on healthcare, specifically the manufacture of medicinal compounds and therapeutic proteins. These are already largely made using biological systems, but the existing processes are expensive and complicated. Also, in the future, it would be more efficient to make these medicines as and when they are needed (point-of-care manufacture). Our goals are to make simpler, more cost effective, point-of-care manufacturing systems using a combination of the above mentioned platform technologies: enzyme microreactors, cell-free protein production systems, and biosensors. 

Model-driven optimisation of bioprocess design

PhD student: Mr Pavlos Kotidis

One of the most important post-translational modifications for the efficacy and safety of the final product is N-linked glycosylation. The glycan that is attached to the constant region of the mAb is known to have a significant impact on its potency. Galactose and uridine lead to increased UDP-Gal intracellular concentration, the nucleotide sugar donor that delivers the galactose residue to the growing oligosaccharide chain. However, precursor addition can perturb cell metabolism and halt cell proliferation. There is therefore a trade-off between positive effects on the glycan profile and potential negative effects on cell growth, which can, in turn, impact on product titre. Following the Quality by Design (QbD) paradigm where the desired quality of the final product is determined at the process design stage, controlling the glycosylation of the produced mAb is of great interest.In this project, we are developing a mechanistic mathematical model that describes CHO cell growth and metabolism, nucleotide sugar donors synthesis and mAbs N-linked glycosylation for different galactose and uridine feeding strategies and are using it for optimal process design.

 

NSD

The metabolic pathway of mammalian nucleotide sugar metabolism



Controlling Fab Terminal Sialylation of antibodies

PhD student: Mr Calum McIntosh

In collaboration with Dr. Karen Polizzi and MedImmune

20% of all IgG antibodies contain Fab glycans. Glycans are composed of a range of sugars whose presence or absence affects the biological qualities of a drug.  Sialic acid is one such sugar; its role is to “cap” the glycan chain, protecting the internal sugars, which when exposed are bound by receptors and cleared to host lysosomes. The presence of sialic acid is linked to an increase in biologic half-life along with a reduced inflammatory response. In this work, we are investigating the effect of cell culture temperature and pH as well as a range of cell line engineering strategies on glycan composition, sialic acid content and site occupancy.

Towards advanced modelling of whole bioprocesses

 PhD student: Mr Sakhr Alhuthali

There is a rising concern of downstream performance being affected by composition of the process lines, which is primarily determined by the upstream activities. However, knowledge on dynamics between the upstream and downstream operations has not yet been explored. It is therefore an untapped research in the biopharmaceutical field to understand the integration and communication between these two operations, leading to the main research objective of this PhD - to develop a robust framework for analysing and simulating the cell culture process with respect to the build-up of host cell protein impurities, which enables us to analyse how upstream decisions impact downstream performance according to the concept of Quality by Design.

Alumni

Dr. Cher Goey (2018)

PhD: Cascading effects in bioprocessing: the impact of cell culture environment on CHO cell behaviour and host cell protein species

Dr. Kristian Mc Caul (2017)

PhD: A platform for the optimisation of metabolic pathways for glycosylation to achieve a narrow and targeted glycoform distribution

Dr. Susie Nga Sou (2016)

PhD: Understanding the impact of bioprocess conditions on monoclonal antibody glycosylation in mammalian cell cultures through experimental and computational analyses

Dr. Philip Jedrzejewski (2016)

PhD: A platform for the optimisation of metabolic pathways for glycosylation to achieve a narrow and targeted glycoform distribution

Dr. Ioanna Stefani (2015)

PhD: Unravelling the role of endoplasmic reticulum stress in familial Alzheimer's Disease  

Dr. Sarantos Kyriakopoulos (2014)

PhD: Amino acid transport and metabolicm in CHO cells

Dr. Ali Behjousiar (2014)

PhD: In situ FRET biosensors for the in vivo measurement of metabolites during cell culture

Dr. Kate Royle (2014)

PhD: Improving the specific productivity of Pichia pastoris

Dr. Ning Chen (2013)

PhD: Modelling of protein-producing Chinese hamster ovary cells (in collaboration with Lonza Biologics)

Dr. Ioscani Jimenez del Val (2013)

PhD: Assessment of the interactions between bioprocess conditions and protein glycosylation in antibody-producing mammalian cell cultures

Ms. Ioanna Psygka (2014)

MSc: Designing an artificial Golgi reactor

Mr. Albert Garcia Madrid (2014)

MSc: The effects of mild hypothermia in GS-CHO fed-batch culture

Mr. Sambit Ghosh (2013)

MSc: Advanced modelling of whole bioprocesses

Mr. François-Xavier Blaudin de The (2012)

MSc: Computational analysis of the role of ER stress in Alzheimer’s disease

Mr. Andrew Nosakhare Amenaghawon (2010)

MSc: Evaluation of ethanol stripping from fermenters

Mr. Themis Kyprianou (2010)

MSc: Designing artificial signalling networks to detect and correct protein aggregation

Mr. John Bender (2009)

MSc: Optimization of Productivity of antibody-secreting mammalian cell cultures

Mr. Rahul Bagga (2009)

MSc: Model-Based analysis of nutrient membrane transport and cell metabolism

Research Staff

Constantinou,A

Fadda,S

Klymenko,O

Niu,H

Penumathsa,B