Prof. Chris Lowe
Director of the Institute of Biotechnology, Professor of Biotechnology
|Qualifications/honours||OBE, FREng, FInstP, FRSC
Pierce Award for Outstanding Contributions to the Field of Affinity Chromatography, 1989
David Curnow Prize in Clinical Chemistry, 1991
Schlumberger Stichting Prize, 1994
Queen's Award for Technological Achievement, 1996
Silver Jubilee Medal - Chromatographic Society, 2002
Fellow, Russian Academy of Medical Sciences, 2002
Henry Dale Medal and Prize: The Royal Institution (London), 2003
Life Membership: The Royal Institution (London), 2003
Royal Society of Chemistry Industrially-Sponsored Award in Sensors: Medal and Prize, 2005
Dade-Behring Award for Clinical Chemistry, 2006
"Most Entrepreneurial Scientist of the UK" Award: UKSEC, 2006
Queen's Anniversary Prize for Higher and Further Education: The Royal Anniversary Trust, 2007
|Address|| Department of Chemical Engineering and Biotechnology
(previously Institute of Biotechnology)
University of Cambridge
Tennis Court Road
|Telephone||+44 (0)1223 (3)34157|
|Research group||Healthcare Biotechnology|
|Themes||Modelling, Measurement, Microstructure Engineering, Processes, Biotechnology|
Research descriptionMy group's primary research interest is in healthcare biotechnology, particularly where it is applied to the high-value low-volume sectors of biopharmaceuticals, sensors and diagnostics and microbial technology. The work is highly multidisciplinary and not only covers aspects of molecular biology, biochemistry, microbiology, chemistry, physics, electronics and engineering, but also the entire range from fundamental science to strategic and applied science, much of which has significant commercial application.
My group has been involved since 1970 in the development of a variety of novel high-resolution affinity techniques for the purification of high value biopharmaceutical proteins. Global markets in excess of $100B currently exist for highly purified antibodies, growth factors, cytokines, hormones, clotting factors, fibrinolytics, erythropoietin, vaccines, diagnostic enzymes, peptides, oligonucleotides and whole genes. It is estimated that within a decade, 25% of all pharmaceuticals will belong to this class of so-called information-rich drugs. However, healthcare providers are forcing pharmaceutical manufacturers to reduce the cost of drugs. In response to the pressure, most biotechnology companies are focusing primarily on bioprocess development as a means of increasing efficiency, reducing production costs and imparting a greater manufacturing flexibility. Furthermore, all steps in the production of biopharmaceuticals must be in compliance with cGMP and with current guidelines issued by the FDA and similar agencies elsewhere. Thus, biological molecules isolated from natural, recombinant or transgenic sources must be shown to have acceptably low levels of host proteins, DNA, pyrogens, prions, leachates from the separation media and viruses. In addition to these purity criteria, regulatory reform is introducing new paradigms, such as the concept of the "well-characterised biologic". This concept requires that the biological molecule be characterised for its identity, purity, impurity profile and potency, including determination of the structure and quantification of the purity, with the impurities quantified and, where possible, identified. Regulatory reform for well-characterised biologics is likely to stimulate the development of new high-resolution separation processes. Of particular concern is the resolution and purification of variants of the target itself, resulting from differences in glycosylation, folding, sequence, oxidation and a multitude of other post-translational modifications. Heterogeneity originates from a number of sources, some of which arise during the expression of the protein, while others are generated during particular downstream operations. Isoforms may be generated by truncation caused by errors in processing the protein during secretion, during accumulation or from side reactions associated with cleavage of a co-expressed fusion protein, by misfolding during in vitro refolding of the target protein after production in a denatured form by certain, especially bacterial, expression systems or by post-translational modifications such as glycosylation, phosphorylation, sulphation and myristoylation. The ability to resolve such heterogeneity is crucial for biopharmaceuticals since product registration is based on a particular isoform composition. More robust processes are required in order to resolve the authentic structure from others in the downstream processing steps. The key drivers for the bioprocessing industry of reducing costs, achieving greater manufacturing flexibility, coupled with the impact of the human genome project, regulatory and environmental changes and the implications of the concept of the well-characterised biologic all present new challenges to the bioprocess engineer.
My group has been involved in the development of highly selective separation technologies based on affinity chromatography since inception of the technique in 1967. The first monograph in this subject was authored by myself and published in 1974 and is still regarded as the standard text. Over the years we have introduced new concepts such as immobilised coenzymes and "group specific" adsorbents, "biomimetic" ligands and the notion of de novo ligand design and intelligent combinatorial libraries. Current work is aimed at exploiting computer-aided molecular design and rational combinatorial chemistry for the development of affinity adsorbents for target biopharmaceuticals, particularly clotting factors and immunotherapeutics, developing techniques for the resolution of variants and post-translational isoforms, introducing novel combinatorial chemistries using multi-component Ugi-Passerini reactions and developing new methods for fractionating the human serum proteome.
This work was acknowledged by receipt of the Queen's Award for Technological Achievement in 1996 in recognition of both the significance of the scientific advance and its commercial success. I have been awarded the Jubilee Silver Medal of the Chromatographic Society in 2002. It is generally accepted that this work will become the gold standard procedure in use worldwide for selective processing of high value biopharmaceuticals.
Biosensors and Diagnostics
My group has been heavily committed to promoting the imaginative combination of biological science with electronics and materials science for the development of novel biosensors and diagnostics. The requirement for chemical intelligence is particularly acute in human healthcare and veterinary medicine, the agri-food, pharmaceutical and petrochemical industries environmental monitoring, defence and security. The development of biosensor technology has promulgated the emergence of "alternate site" diagnostic testing in the ward, outpatients, surgery, home, field or workplace. Much of my groups' activities have been directed towards the development of new technologies applicable to sensors that may be applied in an "alternate site" format. Thus, the group has pioneered a number of developments in biosensor technology over the last two decades, including concepts based on optoelectronics, SPR, conductance, fibre optics, acoustic waveguides, resonant mirrors, micromachined, electromagnetic and holographic devices, and a host of underpinning technologies designed to immobilise, spatially arrange and orientate biological molecules on transducer surfaces. These fundamental studies at the interface of biology with microelectronics, physics and materials science have been extended into new sensor technologies based on holography, including a holographic "virtual" instrument and the use of holographic optical elements, new self-assembling grating fabrication techniques, high frequency acoustics, miniaturised NMR and the use of piezoelectric nanomaterials as nanosensors. Current work is aimed at developing novel technologies for multiplexed assays, point-of-care, developing world and real-time continuous monitoring of patients suffering debilitation diseases.
This combination of new transducer and underpinning technologies, with financial support from the BBSRC and many other organisations, has led to tangible deliverables, including the formation of three new companies, Affinity Sensors Ltd (formerly Fisons Applied Sensor Technology Ltd), Cambridge Sensors Ltd (formerly Environmental Sensors Ltd), Smart Holograms Ltd, Rebha Ltd and Paramata Ltd.
Enzyme, Protein and Microbial Technology
My group has accrued considerable expertise in enzyme and microbial technology over the last 15-20 years and has a special interest in coenzyme-requiring enzymic processes for application in biotransformations and biosensors. Much of this work originated in early work on immobilised nicotinamide nucleotide coenzymes (NAD(P)(H)) for applications in affinity chromatography, although it was quickly realised that such systems had significant implications in enzyme technology if such immobilised coenzymes were coenzymically active. More recently, a programme on biomimetic coenzymes designed to synthesise novel durable redox coenzymes based on a template molecule, the blue textile dye, Cibacron Blue F3G-A, led subsequently to the use of computer-aided molecular design to generate redox coenzymes de novo. More recent work has exploited microorganisms as a source of novel enzymes for use in biosensors for illicit drugs, heavy metals and other analytes of interest to the oil exploration industry. In current work, we are pioneering the use of nano-scale reactors and are engaged in a fundamental study of germinant receptor function in spore germination. This study is expected to lead to new rapid diagnostics for sporogenic pathogens, potential vaccines and more rational decontamination procedures.
Research keywordsAcoustics, affinity chromatography, antibodies, biopharmaceuticals, biosensors, holography, sporogenic organisms
Glucose-Sensitive Holographic Sensors for Monitoring Bacterial Growth. M-C Lee, S. Kabilan, A. Hussain, X. Yang, J. Blyth and C.R. Lowe (2004) Anal. Chem. 76, 5748-5755.
Artificial Protein L for the Purification of Immunoglobulins and Fab-fragments by Affinity Chromatography. A. C. A. Roque, M.A. Taipa and C.R. Lowe (2005) J. Chromatogr. A, 1064, 157-167.
Designed Boronate Ligands for Glucose-Selective Holographic Sensors. X-P Yang, M-C Lee, F. Sartain, X. Pan and C.R. Lowe (2006) Chemistry - A European Journal, 12, 8491-8497.
A Holographic Lactate Sensor. F. Sartain, X-P Yang and C.R. Lowe (2006) Anal. Chem. 78, 5664-5670.
Complexation of L-Lactate with Boronic Acids: A Combined NMR and Holographic Analysis. F.K. Sartain, X-P Yang and C.R. Lowe (2008) Chemistry - A European Journal 14, 4060-4067.
Evidence for a Cross-Linking Mechanism Underlying Glucose-Induced Contraction of Phenylboronate Hydrogels. X. Pan, X. Yang and C.R. Lowe (2008) J. Mol. Recognit. 21, 205-209.
A Novel Encoded and Multiplexed SPR Sensor Platform. K. F. Kastl, C. R. Lowe and C. E. Norman (2008) Anal. Chem. 80, 7862-7869.
Amino Acid Substitutions in Transmembrane Domains 9 and 10 of GerVB that Affect the Germination Properties of Bacillus megaterium Spores.G. Christie and C.R. Lowe (2008) J. Bacteriol. 190, 8009-8017.
Affinity Ligands for Immunoglobulins Based on the Multicomponent Ugi Reaction. J. M. Haigh, A. Hussain, M. L. Mimmack and C. R. Lowe (2009) J Chromatogr B Analyt Technol Biomed Life Sci., 877, 1440-1452.
Holographic Enzyme Inhibition Assays for Drug Discovery. Eu Vian Tan and C.R. Lowe (2009) Anal. Chem. 81, 7579-7589.
Holographic Sensors for Hydrocarbon Gases and Other Volatile Organic Compounds. J.L. Martinez-Hurtado, C.A.B. Davidson, J. Blyth and C.R. Lowe (2010) Langmuir, 26, 15694-15699.
Identification of a Receptor Subunit and Putative Ligand-Binding Residues involved in the Bacillus megaterium QM B1551 Spore Germination Response to Glucose. G. Christie, H. Götzke and C.R. Lowe (2010) J Bacteriol. 192, 4317-4326.
Label-Free Genetic and Proteomic Marker Detection within a Single Flow-Cell Assay.K.F. Kastl, C.R. Lowe and C.E. Norman (2010) Biosens. Bioelectron. 26, 1719-1722.
Mutational Analysis of Bacillus megaterium QM B1551 Cortex-Lytic Enzymes.G. Christie, F.I. Ustok, Q. Lu, L.C. Packman and C.R. Lowe (2010) J. Bacteriol. 192, 5378-5389.