The focus of this module is to provide students with an up-to-date, detailed knowledge of upstream and downstream processing technology, within an international bioindustry context. Spanning the production of biomolecules of relevance to both the pharmaceutical (‘red’) and industrial (‘white-grey’) biotechnology sectors, and with a specific emphasis on mammalian and microbial cell biosystems, a key goal is to convey the integrated nature of modern bioprocess development. Students who complete this module will be equipped with a knowledge and understanding of mainstream bioprocess design heuristics so that they may engage productively within multidisciplinary process development teams.
1: Market perspectives: from ‘cell’ to ‘sell’: Module introduction and orientation regarding scope of course and information resources. The evolving relationship between enabling bioprocess innovation and industrial requirements: how the market defines early stage research and development goals. Production cost–economic analysis of different product classes, interfaced with required return-on-investment.
2. Choice of cell factory for bioprocesses: Factors influencing the choice of in vitro cell production platforms for industrial processes: comparison of bacteria, yeasts, filamentous fungi and mammalian cells.
3. Human health biopharmaceutical production: A technical and market review of the different classes of biologicals, encompassing an upstream bioprocess design perspective. The production and characterization of a selection of the following biopharmaceuticals will be studied: therapeutic monoclonal antibodies, cytokines, growth factors, hormones; blood product/enzymes and vaccines.
4. Large scale mammalian cell culture technology for biopharmaceutical production I: Cell nutrition and growth: Cell nutrition, physiology and growth requirements (contrasted with microbial systems). An overview of culture media formulation and the role of each component. Overflow metabolism and strategies for control. Strategies for optimizing medium compositions.
5. Large scale mammalian cell culture technology for biopharmaceutical production II: Culture modes and bioreactor design configurations beyond the stirred tank reactor: Mammalian cell bioreactor types: design principles and control of the physical-chemical environment. Design and use of microcarriers. Disposable technologies.
6. Downstream processing: Definitions of product purity according to industry sector. General heuristics for designing protein purification schemes, with an integrated consideration of biomolecule properties and cost-effectiveness of different purification technologies. Cell separation-harvesting. Cell disruption. Product isolation from clarified aqueous phase (dewatering). Product purification by chromatography. Whole broth processing. Membrane adsorption chromatography.
7. Biopharmeceutical process characterization case study: Production of recombinant coagulation Factor IX (Benefix®).
8. Mutation breeding for over-production of primary and secondary metabolites: Classical mutagenesis and directed selection strategies in the context of the microbial control of metabolite production. Removal of induction control in catabolic enzymes. Overcoming catabolite repression. Over-production of primary metabolites. Over-production of secondary metabolites. Directed evolution.
9. Metabolic engineering of enzymes by directed mutagenesis and gene editing: PCR-based methods. Original single primer (M13) approaches. CRISPR-Cas-9; Zinc Finger Nucleases; Transcription Activator-like Effector-based Nucleases.
10. Studies in industrial biotechnology manufacturing I: Microbiological processes for the production of amylases. Enzyme requirements for use in detergents, starch processing, bakery products, textiles and the paper industry. Protein engineering for improved performance.
11. Studies in industrial biotechnology manufacturing 2: Microbiological processes for the production of proteases. Enzyme requirements for use in detergent industries. Protein engineering of subtilisins for improved performance.
12. Studies in industrial biotechnology manufacturing 3: Microbiological processes for the production of amino acids. Regulation of amino acid synthesis in the cell. Over-production of amino acids by mutation- selection. Detailed review of processes for industrial scale production of L-lysine and L-glutamate.
Practical Programme
Production of streptavidin using the filamentous prokaryote, Streptomyces avidinii, grown in stirred tank bioreactor.
Investigation of the principles of preparative and analytical glycobiology using a model glycoprotein, Ribonuclease B (exo-glycosidase digestion of glycoprotein followed by electrophoresis).
1: Market perspectives: from ‘cell’ to ‘sell’
Module introduction and orientation regarding scope of course and information resources. The evolving relationship between enabling bioprocess innovation and industrial requirements: how the market defines early stage research and development goals. Production cost–economic analysis of different product classes, interfaced with required return-on-investment.
2. Choice of cell factory for bioprocesses
Factors influencing the choice of in vitro cell production platforms for industrial processes: comparison of bacteria, yeasts, filamentous fungi and mammalian cells.
3. Human health biopharmaceutical production
A technical and market review of the different classes of biologicals, encompassing an upstream bioprocess design perspective. The production and characterization of a selection of the following biopharmaceuticals will be studied: therapeutic monoclonal antibodies, cytokines, growth factors, hormones; blood product/enzymes and vaccines.
4. Large scale mammalian cell culture technology for biopharmaceutical production I
Cell nutrition and growth: Cell nutrition, physiology and growth requirements (contrasted with microbial systems). An overview of culture media formulation and the role of each component. Overflow metabolism and strategies for control. Strategies for optimizing medium compositions.
5. Large scale mammalian cell culture technology for biopharmaceutical production II
Culture modes and bioreactor design configurations beyond the stirred tank reactor: Mammalian cell bioreactor types: design principles and control of the physical-chemical environment. Design and use of microcarriers. Disposable technologies.
6. Downstream processing
Definitions of product purity according to industry sector. General heuristics for designing protein purification schemes, with an integrated consideration of biomolecule properties and cost-effectiveness of different purification technologies. Cell separation-harvesting. Cell disruption. Product isolation from clarified aqueous phase (dewatering). Product purification by chromatography. Whole broth processing. Membrane adsorption chromatography.
7. Biopharmaceutical process characterization case study
Production of recombinant coagulation Factor IX (Benefix®).
8. Mutation breeding for over-production of primary and secondary metabolites
Classical mutagenesis and directed selection strategies in the context of the microbial control of metabolite production. Removal of induction control in catabolic enzymes. Overcoming catabolite repression. Over-production of primary metabolites. Over-production of secondary metabolites. Directed evolution.
9. Metabolic engineering of enzymes by directed mutagenesis and gene editing
PCR-based methods. Original single primer (M13) approaches. CRISPR-Cas-9; Zinc Finger Nucleases; Transcription Activator-like Effector-based Nucleases.
10. Studies in industrial biotechnology manufacturing I
Microbiological processes for the production of amylases. Enzyme requirements for use in detergents, starch processing, bakery products, textiles and the paper industry. Protein engineering for improved performance.
11. Studies in industrial biotechnology manufacturing 2
Microbiological processes for the production of proteases. Enzyme requirements for use in detergent industries. Protein engineering of subtilisins for improved performance.
12. Studies in industrial biotechnology manufacturing 3
Microbiological processes for the production of amino acids. Regulation of amino acid synthesis in the cell. Over-production of amino acids by mutation- selection. Detailed review of processes for industrial scale production of L-lysine and L-glutamate.
Practical Programme
Production of streptavidin using the filamentous prokaryote, Streptomyces avidinii, grown in stirred tank bioreactor.Investigation of the principles of preparative and analytical glycobiology using a model glycoprotein, Ribonuclease B (exo-glycosidase digestion of glycoprotein followed by electrophoresis).
Learning outcomes will be primarily achieved through lectures and laboratory exercises, complemented by a case study (report assignment, student presentation and discussion group), self-directed learning and in-course assessment.
| Module Content & Assessment | |
|---|---|
| Assessment Breakdown | % |
| Formal Examination | 60 |
| Other Assessment(s) | 40 |