Biological Systems Engineering

The Biological Systems Engineering group within the Sargent Centre focuses on the development of mathematical models for biological systems. Topics of interest include industrial biotechnology, bioprocessing, systems biology and biomedical systems. Recent projects received significant funding from the Research Councils and the European Research Council and saw closer collaboration between Imperial and UCL in this research field.

Selected examples from the current project portfolio on biomedical systems are listed below:

Dr Vivek Dua is working on ion transport modelling for cystic fibrosis.

Cystic fibrosis (CF) is genetic disease of the lung. Dr Dua’s team have developed a mathematical model of the ion transport for CF patients, which shows that loss of apical chloride permeability alone cannot explain the observed voltage data, but an increased apical sodium permeability must also take place. This insight opens up new avenues for potential therapies for the CF.

Professor David Bogle is collaborating with researchers in UCL’s Cancer Institute on network analysis of DNA damage response and cellular signalling in different KRAS mutated colorectal cancer cell lines. Personalized treatments have been postulated as the way forward in treating most types of cancer. This project has developed a systems analysis approach to the problem using gene expression microarray technology to explore the difference between different metastatic colorectal cancer cell lines in order to expose potential diagnostic measures and explain the response to different treatments.

The groups of Professors Pistikopoulos and Mantalaris are working on a number of biomedical systems, including cancer treatment and anaesthesia control. Specifically, Acute Myeloid Leukaemia (AML) is a subtype of blood cancer which only affects cells belonging to the myeloid lineage. The prescribed treatment is chemotherapy scheduled in several cycles. The mechanism behind drug action requires cell proliferation. AML cells are indeed highly proliferative and will be targeted by the drug; however, other stem cells that are actively duplicating in order to regenerate healthy cellular material will also be affected. It is thus critical to reach a trade-off between killing cancer cells and keeping a minimum number of healthy cells. In that direction, the research team is building a model based on patient- and disease- specific characteristics in order to design more rational chemotherapy protocols that are less risky and milder for the patient. In parallel, the group is developing modelling, optimisation and explicit model predictive control strategies for anaesthesia drug delivery systems. Closed-loop model predictive control strategies for anaesthesia are aimed at improving patient safety and to fine-tuning drug delivery, routinely performed by the anaesthetist.

Professor David Bogle is working with colleagues in UCL’s Hepatology Department on understanding the function of the liver in health and disease. Firstly, they are following a combined computational modelling and experimental approach to assess the role of metabolic zonation across the sinusoid in healthy liver and the consequences of its dysregulation in disease. Their research focuses in particular on carbohydrate and lipid metabolism. Secondly, they are exploring the possibility of using a new biomaterial as a cell support in bioartificial liver using the zonated
model. They are investigating if cells can be grown throughout the cryogel support in the artificial organ, if they show signs of cell-cell communication, and whether they retain liver specific function over a period of time.

Dr Krishnan’s group is working on the development of a multiscale/multilevel modelling framework for elucidating the effects of intrinsic and induced drug resistance in solid tumours at the cell and tissue scale, as well as developing an integrated framework for combined drug transport in the blood, interstitium and its effect on and interplay with cellular factors.

In Industrial Biotechnology and Bioprocessing, we have several projects including the following:

Professors Pistikopoulos and Mantalaris are developing population balance models for cell culture systems. The objective of their research is the development of a framework, experimental and mathematical, that facilitates the study of mammalian cell cultures as a sum of subpopulations with individual growth/metabolic and productivity characteristics. They are also involved in model-based optimization and control for process intensification in chemical and biopharmaceutical systems. Process Intensification (PI) is the response to world-wide changes in the chemical/biopharmaceutical industry for specific end-use product properties and stricter energy and environmental constraints. In this framework, research aims to overcome the limitations on implementing PI by establishing a new methodological design approach for sustainable, intensified chemical/biopharmaceutical plant design. Within this scope, four specific processes (Chromatography, Polymerization, Crystallization, Oxidation) are examined in detail.

Research in Dr Krishnan’s group has focussed on signal transduction and gene regulatory networks/processes and their control of cellular processes of basic and applied interest. It involves modelling in collaboration with experimentalists (cell biologists, biomedical scientists, synthetic biologists). Activities include modelling feedback regulation of protein synthesis at the translation stage, the development of new probabilistic Boolean networks based modelling approaches for modelling translation; tools for dissecting the complexity of translation in systems and synthetic biology, spatial control of signal transduction in signalling modules and networks and information processing in complex biochemical mechanisms: multi-site phosphorylation.

Dr Cleo Kontoravdi and colleagues in Life Sciences are examining the impact of bioprocess conditions on protein product quality using modelling and experimentation. Their most recent work focuses on developing dynamic metabolic flux analysis approaches in order to quantitatively determine the impact of nutrient availability on protein glycosylation. In parallel, they have developed algorithms for media and feed formulation for Chinese hamster ovary cell culture.

Professor Nilay Shah and Dr Cleo Kontoravdi are working with colleagues at UCL’s Biochemical Engineering and Chemistry Departments on the manufacture of chemicals and pharmaceutical intermediates from sugar beet pulp. The research team is evaluating the process economics, energy and carbon balances for potential novel flowsheets, while setting up unit operations and process models to develop whole system models and perform life cycle analysis.

Finally, Professor Shah and Dr Kontoravdi are involved in the recently awarded Frontier Manufacturing award in Synthetic Biology. The goal is to drive a paradigm shift in the industrial scale production of chemicals, therapeutics, fuels and materials, revolutionising the translation and commercial exploitation of advances in biosciences and physical sciences through synthetic biology. At the heart of this approach is the application and integration of new synthetic biology production vectors into novel process technologies, thereby dovetailing cutting edge biological and chemical transformations.