Professor Michael Bushell
Professor of Microbiology
Email: m.bushell@surrey.ac.uk
Phone: Work: 01483 68 9277
Room no: 04 AW 01
Office hours
Mon-Fri 9-5.30 by appointment only.
Further information
Biography
I am Professor of Microbiology in the Microbial Sciences Division, where I was formerly Head of Division. Prior to joining the University, I worked in the Pharmaceutical industry (Pfizer and GSK). I did my PhD with Alan Bull at the University of Kent on the physiology of Aspergillus nidulans in chemostat culture and my first degree (in Microbiology) at Kings College London.
I am currently a member of the BBSRC IBTI committee and the Food Standard Agency ACNFP committee and the External Advisory Group for the Applied Biotechnology Research Cluster of the University of Westminster.
I live in Farnham with Carole and my hobbies include skiing, football, rugby, music, theatre, dancing and hanging out with friends in bars and cafes.
Research Interests
My current interests involve genome scale metabolic network modeling and advanced bioreactor technology applied to the physiology of a range of microorganisms.
Specific topics include antibiotic biosynthesis, bioreactor performance and micro-morphology of Streptomyces, recombinant protein production in Pichia pastoris and the role of Pseudomonas infections in cystic fibrosis.
Current grants
| Growth-associated gene essentiality in Streptomyces | BBSRC | £341,559 PI |
| In silico study of lignocellulosic biofuel processes | BBSRC | £446,778 PI |
The interplay between two-component signal transduction systems and genome scale metabolic in S.coelicolor | BBSRC | £714,859 CoI |
| BBSRC | £530,000 CoI |
| Metabolic engineering of Streptomyces | Eli Lilly | £90,000 PI |
Recently completed grants:
Development of a transcriptome-constrained genome-scale bioreaction network to provide an in silico model of cell metabolism with predictive power for secondary metabolism in Streptomyces coelicolor.
BBSRC £256,035 PI
Actinogen-integrating genomics-based applications to exploit actinomycetes as a resource for new antibiotics EU £452,987 CoI
Influence of morphology on bioreactor performance of antibiotic-producing micro-organisms Abbott Laboratories, Chicago £90,000 PI
Research Collaborations
Prof C P Smith
Prof JJ McFadden
Dr A Keirzek
Dr G Stewart
Publications
Journal articles
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(2011) 'New Approach To Produce Water Free of Bacteria, Viruses, and Halogens in a Recyclable System'. AMER SOC MICROBIOLOGY APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 77 (3), pp. 847-853.doi: 10.1128/AEM.01645-10Full text is available at: http://epubs.surrey.ac.uk/7417/
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(2011) 'Metabolomic Profiling Can Differentiate Between Bactericidal Effects of Free and Polymer Bound Halogen'. WILEY-BLACKWELL JOURNAL OF APPLIED POLYMER SCIENCE, 119 (2), pp. 709-718.doi: 10.1002/app.32731
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(2011) 'Genome-wide transcriptomic analysis of the response to nitrogen limitation in Streptomyces coelicolor A3(2).'. BMC Res Notes, England: 4Full text is available at: http://epubs.surrey.ac.uk/203297/
Abstract
The present study represents a genome-wide transcriptomic analysis of the response of the model streptomycete Streptomyces coelicolor A3(2) M145 to fermentor culture in Modified Evans Media limited, respectively, for nitrogen, phosphate and carbon undertaken as part of the ActinoGEN consortium to provide a publicly available reference microarray dataset.
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(2011) 'Acorn: a grid computing system for constraint based modeling and visualization of the genome scale metabolic reaction networks via a web interface.'. BioMed Central BMC Bioinformatics, England: 12 (196)Full text is available at: http://epubs.surrey.ac.uk/185976/
Abstract
Constraint-based approaches facilitate the prediction of cellular metabolic capabilities, based, in turn on predictions of the repertoire of enzymes encoded in the genome. Recently, genome annotations have been used to reconstruct genome scale metabolic reaction networks for numerous species, including Homo sapiens, which allow simulations that provide valuable insights into topics, including predictions of gene essentiality of pathogens, interpretation of genetic polymorphism in metabolic disease syndromes and suggestions for novel approaches to microbial metabolic engineering. These constraint-based simulations are being integrated with the functional genomics portals, an activity that requires efficient implementation of the constraint-based simulations in the web-based environment.
- . (2010) 'SurreyFBA: a command line tool and graphics user interface for constraint-based modeling of genome-scale metabolic reaction networks'. OXFORD UNIV PRESS BIOINFORMATICS, 27 (3), pp. 433-434.
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(2010) 'Macroscopic N-Halamine Biocidal Polymeric Beads'. JOHN WILEY & SONS INC JOURNAL OF APPLIED POLYMER SCIENCE, 116 (4), pp. 2396-2408.doi: 10.1002/app.31774
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(2009) 'Optimizing Halogenation Conditions of N-Halamine Polymers and Investigating Mode of Bactericidal Action'. JOHN WILEY & SONS INC JOURNAL OF APPLIED POLYMER SCIENCE, 113 (4), pp. 2404-2412.doi: 10.1002/app.30390
- . (2008) 'Biocidal polymers (II): Determination of biological activity of novel N-halamine biocidal polymers and evaluation for use in water filters'. ELSEVIER SCIENCE BV REACTIVE & FUNCTIONAL POLYMERS, 68 (10), pp. 1448-1458.
- . (2008) 'Selection of objective function in genome scale flux balance analysis for process feed development in antibiotic production'. ACADEMIC PRESS INC ELSEVIER SCIENCE METABOLIC ENGINEERING, 10 (5), pp. 227-233.
- . (2008) 'Biocidal polymers (I): Preparation and biological activity of some novel blocidal polymers based on uramil and its azo-dyes'. ELSEVIER SCIENCE BV REACTIVE & FUNCTIONAL POLYMERS, 68 (1), pp. 248-260.
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(2007) 'Transcriptomic analysis identifies growth rate modulation as a component of the adaptation of mycobacteria to survival inside the macrophage'. AMER SOC MICROBIOLOGY JOURNAL OF BACTERIOLOGY, 189 (11), pp. 3969-3976.doi: 10.1128/JB.01787-06Full text is available at: http://epubs.surrey.ac.uk/184935/
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(2007) 'GSMN-TB: a web-based genome scale network model of Mycobacterium tuberculosis metabolism'. BIOMED CENTRAL LTD GENOME BIOLOGY, 8 (5) Article number ARTN r89 Full text is available at: http://epubs.surrey.ac.uk/184904/
- . (2006) 'The use of genome scale metabolic flux variability analysis for process feed formulation based on an investigation of the effects of the zwf mutation on antibiotic production in Streptomyces coelicolor'. ELSEVIER SCIENCE INC ENZYME AND MICROBIAL TECHNOLOGY, 39 (6), pp. 1347-1353.
- . (2006) 'Fed batch culture with declining specific growth rate for high-yielding production of a plasmid containing a gene therapy sequence in Escherichia coli DH1'. ELSEVIER SCIENCE INC ENZYME AND MICROBIAL TECHNOLOGY, 39 (1), pp. 47-50.
- . (2006) 'Manipulation of the physiology of clavulanic acid biosynthesis with the aid of metabolic flux analysis'. ELSEVIER SCIENCE INC ENZYME AND MICROBIAL TECHNOLOGY, 39 (1), pp. 149-157.
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(2005) 'Compiling a molecular inventory for Mycobacterium bovis BCG at two growth rates: evidence for growth rate-mediated regulation of ribosome biosynthesis and lipid metabolism.'. J Bacteriol, United States: 187 (5), pp. 1677-1684.Full text is available at: http://epubs.surrey.ac.uk/184910/
Abstract
An experimental system of Mycobacterium tuberculosis growth in a carbon-limited chemostat has been established by the use of Mycobacterium bovis BCG as a model organism. For this model, carbon-limited chemostats with low concentrations of glycerol were used to simulate possible growth rates during different stages of tuberculosis. A doubling time of 23 h (D = 0.03 h(-1)) was adopted to represent cells during the acute phase of infection, whereas a lower dilution rate equivalent to a doubling time of 69 h (D = 0.01 h(-1)) was used to model mycobacterial persistence. This chemostat model allowed the specific response of the mycobacterial cell to carbon limitation at different growth rates to be elucidated. The macromolecular (RNA, DNA, carbohydrate, and lipid) and elemental (C, H, and N) compositions of the biomass were determined for steady-state cultures, revealing that carbohydrates and lipids comprised more than half of the dry mass of the BCG cell, with only a quarter of the dry weight consisting of protein and RNA. Consistent with studies of other bacteria, the specific growth rate impacts on the macromolecular content of BCG and the proportions of lipid, RNA, and protein increased significantly with the growth rate. The correlation of RNA content with the growth rate indicates that ribosome production in carbon-limited M. bovis BCG cells is subject to growth rate-dependent control. The results also clearly show that the proportion of lipids in the mycobacterial cell is very sensitive to changes in the growth rate, probably reflecting changes in the amounts of storage lipids. Finally, this study demonstrates the utility of the chemostat model of mycobacterial growth for functional genomic, physiology, and systems biology studies.
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(2004) 'Characterization of the metabolic burden on Escherichia coli DH1 cells imposed by the presence of a plasmid containing a gene therapy sequence'. JOHN WILEY & SONS INC BIOTECHNOLOGY AND BIOENGINEERING, 88 (7), pp. 909-915.doi: 10.1002/bit.20327
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(2003) 'Cyclic fed-batch culture for production of human serum albumin in Pichia pastoris'. JOHN WILEY & SONS INC BIOTECHNOLOGY AND BIOENGINEERING, 82 (6), pp. 678-683.doi: 10.1002/bit.10616
- . (2002) 'Decreasing the hyphal branching rate of Saccharopolyspora erythraea NRRL 2338 leads to increased resistance to breakage and increased antibiotic production.'. Biotechnol Bioeng, United States: 78 (2), pp. 141-146.
- . (2000) 'Growth limiting substrate affects antibiotic production and associated metabolic fluxes in Streptomyces clavuligerus'. KLUWER ACADEMIC PUBL BIOTECHNOLOGY LETTERS, 22 (22), pp. 1803-1809.
- . (2000) 'The Vancomycin biosynthetic pathway is induced in oxygen-limited Amycolatopsis orientalis (ATCC 19795) cultures that do not produce antibiotic.'. Enzyme Microb Technol, 27 (7), pp. 502-510.
- . (1999) 'Kinetics and manipulation of hyphal breakage and its effect on antibiotic production'. ELSEVIER SCIENCE INC ENZYME AND MICROBIAL TECHNOLOGY, 25 (3-5), pp. 404-410.
- . (1999) 'Sporulation at minimum specific growth rate in Aspergillus nidulans chemostat culture predicted using protein synthesis efficiency estimations.'. J Basic Microbiol, GERMANY: 39 (5-6), pp. 293-298.
- . (1997) 'Manipulation of the physiology of clavulanic acid production in Streptomyces clavuligerus.'. Microbiology, ENGLAND: 143 ( Pt 11), pp. 3573-3579.
- . (1997) 'The effect of morphology and oxygen uptake on penicillin production by Aspergillus nidulans in submerged culture'. CAMBRIDGE UNIV PRESS MYCOLOGICAL RESEARCH, 101, pp. 1237-1241.
- . (1997) 'Effect of small scale culture vessel type on hyphal fragment size and erythromycin production in Saccharopolyspora erythraea'. CHAPMAN HALL LTD BIOTECHNOLOGY LETTERS, 19 (9), pp. 849-852.
- . (1997) 'A physiological model for the control of erythromycin production in batch and cyclic fed batch culture'. SOC GENERAL MICROBIOLOGY MICROBIOLOGY-UK, 143, pp. 475-480.
- . (1996) 'Effect of hyphal micromorphology on bioreactor performance of antibiotic-producing Saccharopolyspora erythraea cultures'. SOC GENERAL MICROBIOLOGY MICROBIOLOGY-UK, 142, pp. 1783-1788.
- . (1995) 'The physiology of erythromycin biosynthesis in cyclic fed batch culture'. SOC GENERAL MICROBIOLOGY MICROBIOLOGY-UK, 141, pp. 3105-3111.
Teaching
First year
Microbiology – microbes and Man; BMS1010
I currently lecture on the use of microbes by Pharma and other Companies for the manufacture of Bioproducts (both biomedical and other products you may not have realised were made by microbes). Click on the links below for further information on these topics.
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LINK2 http://sbms.surrey.ac.uk/default.aspx
Second year
Microbiology Systems; BMS2028
My 12 lectures provide your one stop shop for an introduction to microbial bioproducts, their uses and the tricks we play on the unsuspecting microorganisms to force then to produce what we want.
LINK 1
LINK2 http://sbms.surrey.ac.uk/default.aspx
Third year
Biomedical Microbial Products; BMS3032
This course was designed with consultation with Biotech and Pharma companies. I often get phone calls from potential employers asking me to recommend good students from the course for vacancies in those companies. I take the students to the cutting edge of the science behind bioproducts, integrating the latest findings from my own research where I can.
LINK 1
LINK2 http://sbms.surrey.ac.uk/default.aspx
Practical Microbial Bioproduct Discovery; BMS3031
Originally designed to complement 3032 (which it still synergizes with, this course can now be taken as a stand-alone module. You will be given an example of how to discover new biopharmaceuticals to order.
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