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Biochemical engineering research themes: industrial biotechnology, macromolecular bioprocessing and cell & gene therapy bioprocessing
Industrial biotechnology
The focus is on the efficient synthesis of chemicals and pharmaceuticals from renewable resources. This entails a multidisciplinary approach integrating biological and chemical catalysis with high throughput bioprocess design and scale-up.
This multidisciplinary group focuses on the integration of biological and chemical catalysis for the synthesis of next generation chemicals and pharmaceuticals. In recent years the group has won major awards in the areas of Chemical Biology (Royal Society of Chemistry, 2010), Bioprocessing (Institution of Chemical Engineers, 2010) and for the translation of research into industrial practice (Evonik Science-to-Business award, 2008). Synthetic Biology underpins our research on the discovery and design of biological catalysts for industrial application. This includes aspects of metagenomics, enzyme, pathway and cellular engineering. A wide range of enzymes are under investigation including cytochrome P450s, norcoclaurine synthases, ketone reductases (KREDs), transketolases and transaminases. These are being expressed in a range of chasis organisms including Corynebacterium glutamicum, E. coli and Pichia pastoris.
In parallel we are interested in novel techniques for High Throughput Bioprocess Design, including microfluidic and automated microwell based systems, and novel engineering solutions to enhance reaction productivity e.g. chemo-enzymatic reaction cascades, multi-phase and photobioreactor design, continuous flow reactors and in-situ techniques for substrate supply/product removal. Mathematical modelling approaches aid in efficient experimental design (statistical Design of Experiments, DoE), biocatalyst design and evaluation (metabolic pathway and systems modelling), bioreactor design and scale-up (Computational Fluid Dynamics, CFD) and environmental impact analysis (Life Cycle Analysis, LCA)
Macromolecular bioprocessing
The focus is on the creation of scalable processes for the cost-effective manufacture of macromolecular therapies including proteins, viral vaccines, DNA, and mRNA. This is achieved by using advanced high-throughput engineering tools, and computational modelling, for bioprocess design and scale-up.
Research in Macromolecular Bioprocessing is headed by the £10M EPSRC Future Targeted Healthcare Manufacturing Hub, and also the £7M EPSRC Future Vaccines Manufacturing Hub, hosted in the Department of Biochemical Engineering with collaborations from across UCL (Dept. Public Health Economics) and from Imperial College London, Loughborough University, Manchester University, Nottingham University, Oxford University, Warwick university. The focus is on creating methods and tools to rapidly assess a new molecule’s ease of manufacture and formulation, bioprocess design, and costs of goods. We are also addressing the challenges associated with patient stratification towards potentially personalised medicines. The ultimate objective is to achieve efficient conversion of potent new therapies to the patient at a cost which the NHS can afford.
Key Areas
- Ultra Scale-Down (USD) of key unit operations for the recovery & purification of micromolecules
- Microwell methods for the rapid screening of process options
- Advanced methods for assay deployment and for efficient experimental design
- Decisional tools for the better integration of business and process decision making
- Assessment of manufacturing alternatives including life cycle analysis
- Biophysical characterisation of protein heterogeneity and aggregation mechanisms
- Formulation and protein engineering to maximise product shelf-life
- Machine learning and artificial intelligence for digital data analysis and process control
Cell and gene therapy bioprocessing
Through multidisciplinary collaborations with clinicians and industry, our mission is to provide the research expertise to enable the manufacture of safe, clinically efficacious and cost effective cell therapies for delivery to patients.
The focus of cell therapy bioprocessing activity is to accelerate the safe, clinical efficacious and cost effective translation of cell therapies into commercial products. This activity spans the entire range of cell therapy activities as well as tissue engineering. The distinctive UCL approach involves taking a ‘whole bioprocess’ view from donor or patient biopsy all the way through to clinical implantation into the patient. To date fundamental bioprocess research in collaboration with clinical groups and companies has supported the development and clinical application of various cell therapies. Achievements include preclinical filing for Phase 1 clinical trials for cell therapy in acute spinal cord injury, clinical proof of concept studies in tissue-engineered trachea, clinical trials for tissue-engineered larynx and routine clinical practice in the regeneration of corneas. Future research priorities will focus on novel cell and bioprocess engineering techniques to improve manufacturing efficiency and methods for health technology assessment to support rapid clinical adoption of new cell therapies
Key Areas
- Creation of ultra-scale down and microfluidic methods for early stage bioprocess development
- Design of novel bioreactor and bioprocessing technologies
- Study and optimisation of the impact of oxygen tension on stem cell culture
- Decisional tools research to identify the most cost-effective manufacturing routes for cell therapies
- Healthcare economics