Dr. Michael Butler

Michael Butler
Distinguished Professor
Animal Cell Technology

Department of Microbiology
University of Manitoba,
Winnipeg, Manitoba
CANADA R3T 2N2

Telephone: +1-204-474-6543
FAX: +!-204-474-7603

mailto:butler@cc.umanitoba.ca

Mike Butler outside Buller building

 

 

 

Lab group/ Dept Microbiology

 

 

  

Ben Dionne                                    Carine Villacres                                         Bo Liu

 

 

 

       Katrin Braasch                      Vince Jung                          Sarah Chan                               

 

Maureen Spearman

 

Katrin and the bioreactor

             Analyzing important data                

 

Course in "Animal Cell Technology" at Universidade Federal de Rio da Janeiro, Brazil (2007)

 

Mike Butler/ Brief Profile

Distinguished Professor of Animal Cell Technology, Dept Microbiology, University of Manitoba, Canada (2008-).

Scientific Director of MabNet; NSERC-funded strategic network for the production of single-type glycform monoclonal antibodies (2010-)

Previous academic appointments: Associate Dean (Research), NSERC/ Apotex Industrial Research Chair in Fermentation Technology, University of Manitoba; Principal Lecturer/ Biotechnology at Manchester Metropolitan University; Visiting Scientist/ Professor at MIT, Animal Virus Inst, (Pirbright), University of Oxford & University of Rio de Janeiro.

Qualifications: BSc (Biochemistry, Birmingham), Cert Ed (Birmingham), MSc (Chemistry, U of Waterloo), PhD (Biochemistry, King’s, U of London).

Editor: Biotechnology Advances, Biotechnology and Bioengineering, Encyclopedia of Cell Technology, Open Biotechnology Journals.

Member: Biochemical Society, Canadian Soc. of Microbiology, Canadian. Soc Chemical Engineering, International Soc. for Protein Expression (Board member).  elected to executive committee of European Society of Animal Cell Technology (ESACT), Advisory panel of Cell Culture Engineering

Publications: 7 books, >100 peer-reviewed scientific articles.

Commercial: President of Biogro Technologies Inc. (serum-free media development)

Research interests: animal cell technology, glycosylation, development of mammalian cell culture bioprocesses for scale-up and industrial production

Recent Awards: Winner of the 2004 Synergy Award by NSERC (Canadian Research Council) for innovation involving University-Industry collaboration.

2008: Distinguished Professor award (1 of 20 at University of Manitoba)

Membership of grant awarding agencies: NSERC/ committee on University/Industry grants (Ottawa), NSF/ Small Business Fund (Washington), MHRC/ Health research (Winnipeg), Alberta Ingenuity Fund

International: Chair of organizing committee for Conference on Protein Expression in Animal Cell (PEACe) Angra dos Reis, BRAZIL, September 16-20, 2007;
Leader of Biotechnology sub-group in Canadian government Department of Foreign Affairs mission to Brazil, Advisory panel to Swedish program on Biotechnology at the Stockholm Royal Inst. Technology, Chair of SFI Advisory panel (Dublin, Ireland)

PRESENT RESEARCH ACTIVITY

Mammalian Cell Technology:   The research focuses on strategically important themes in the area of recombinant protein and viral vaccine production from mammalian cell cultures. This includes the use of techniques of biochemistry and cell physiology in the development of bioprocesses for the production of biologicals and biopharmaceuticals. The research activity aims to characterise and control the cell culture process so that product synthesis is maximised. This can be achieved by the enhancement of cell specific protein expression or by attaining high cell densities. The quality of biopharmaceuticals is particularly important to ensure full biological activity and this has encouraged a study of the control of post-translational modification of glycoproteins. The culture systems used in the programme include several commercially important producer lines eg: Vero, MRC-5, BHK, MDCK, CHO and hybridomas.    These include hybridomas that are capable of secreting monoclonal antibodies, transfected cells (eg: CHO) for specific protein expression and Vero (or MRC-5) cells grown on microcarriers which are important for vaccine production. Serum-free formulations have been specifically designed for these cell lines. The rights to the formulations have been transferred to a commercial spin-off company (Biogro Technologies Inc) for which Butler is the major share holder. 

 The scientific challenge for the use of mammalian cells in large-scale processes is the development of robust bioprocesses that favor high productivity from relatively fragile cell lines (Butler, 2005a,b).  

The scope of the present work can be summarised as follows :-

• Glycomics and post-translational modification of products
• Selection and adaptation for robustness
• Metabolic engineering for improved efficiency of energy metabolism
• Serum-free, chemically defined media for cell growth
• Virus production from anchorage-dependent mammalian cells

For an article on the industrial application of the research : taking it from the lab to the drugstore

Recent funding for MabNet:  $5 million over 5 years

RECENT INVITED LECTURES

•   Monitor and control of glycosylation in mammalian cell bioprocesses. Cambridge Healthtech Institute, Boston, USA August  2011
•   Integrating and downstream processing: the production of proteins with a restricted glycoform profile. BioProcess International Conference, Nice April 2011.
•   Controlling PTMs via cell culture. Informa Life Sciences Brussels Sept 2010.
•   Characterization and control of protein glycosylation in cell bioprocesses protein glycosylation in cell bioprocesses Cambridge Healthtech Institute, San Diego April, 2010.
•   Insights into relationship between protein expression and glycosylation profile.  IBC Meeting “Recombinant Protein & Complex Biologic Development & Production.” Carlsbad, CA, March 2010   
• Strategies for enhanced productivity of a hydrophobic recombinant protein.. 9^thConference on Protein Expression in Animal Cells. Jackson Hole, Wyoming USA 2009
• The control of glycosylation in mammalian cell bioprocesses. IBC meeting on Post-translational modification, Prague September 2009
• Control of glycosylation in bioreactors.  Lonza Biologics plc., UK  September 2008
• Cell metabolism and its control in culture. Third International School on Biopharmaceutical production from animal cell cultures.  Federal Universidad de Rio de Janeiro, Brazil. July 2008
• Effects of Cell Culture Conditions on Glycosylation.  IBC Life Sciences conference on Cell line development and Engineering. San Diego. California, June 2008
• Biopharmaceuticals:  production to high yields and good quality.  International Symposium: Challenges in Pharmaceutical Research.  Universidad Autonoma del Estado de Morelos (March 2008).
• What causes altered glycosylation in mammalian cells ?  A study in glycomics.  Pfizer Missouri (June, 2007)
• The effect of culture conditions on the glycosylation of proteins secreted by mammalian cells. IBC Life Sciences conference on Post-translational modification, Prague (Nov 2007). 
• Rational methods of developing cell culture media.  IBC Life Sciences Conference on Cell line Development and Engineering.  La Jolla , California (June 2007)
• Four lectures at Brazilian Universities: Rio de Janeiro, Campinas and Sao Paulo (Feb/March 2007)
• Glycomics as a means to characterize Congenital Disorders of Glycosylation. Dept Pathology, University of  Manitoba (December 2006)
• Current methods for determining glycosylation. Bioprocess International. IBC Life Sciences Conference. San Francisco (November 2006)
• The effect of culture conditions on the glycosylation of proteins secreted by mammalian cells.  Seminario de Instituto de Biotecnologia, Universidad Nacional de Mexico (November, 2006)
• What causes altered glycosylation in mammalian cells ?  A study in glycomics.  Manitoba Centre for Proteomics (April 2006). 
• The effect of micro-nutrients on cellular productivity and metabolism in serum-free media.  Bioprocess International. IBC Life Sciences Conference. Berlin (April 2005) 
• The effect of micro-nutrients on cell metabolism in serum-free media. Transmissible Spongifom Encephalopathies. IBC Life Sciences Conference.  Washington (2004).
• The effect of culture conditions on the glycosylation of proteins secreted by mammalian cells.  3^rd Conference on Recombinant Protein Production. Tavira, Portugal  (November 2004)
• Cell Culture and Upstream Processing. IBC Life Sciences Conference. Boston (October 2004), Berlin (September 2004)
• “Opportunities in animal cell technology”  Meeting for collaboration between Brazil-Canada, Sao Paulo, 2003  
• Culture parameters that cause perturbations in the glycosylation of proteins secreted by mammalian cells.  6^th Conference on Protein Expression in Animal Cells. Mont Tremblant, Quebec 2003
• Protein glycosylation is controlled by cell culture conditions. American Chemical Soc, New Orleans, March 2003
• Culture parameters that cause perturbations in the glycosylation of proteins secreted by mammalian cells. Canadian Society of Chemical Engineering.  Vancouver, Oct 2002
• Recombinant protein production from mammalian cells grown in the Cytopilot fluidized bed bioreactor.  Amersham Biosciences seminars, Piscataway, Philadelphia & New York, Nov 2001
• Congenital Disorders of glycosylation.  Dept Biochemistry, Oxford University  July 2001
• Congenital Disorders of glycosylation  School of Biological Sciences, University of Kent August 2001
• Erythropoietin production from mammalian cells grown in the Cytopilot fluidized bed bioreactor "The solution to your bioprocessing equation". Amersham/Pharmacia Biotech.Montreal & Toronto October 2000
• Parameters that affect the glycosylation of products from mammalian cell culture Biotechnology Research Institute, NRC, Montreal, Canada June 2000.
• “Nutrient requirements for the growth of mammalian cells in culture” and “Development of serum-free media for the growth of Vero cells and production of reovirus”.  Merck Co., Westpoint, May 2000
• New drugs for the future: Biotechnology leads the way into the next millennium.  On the Edge lecture series. University of Manitoba, April 2000
• Production of reovirus from microcarrier cultures of Vero cells. American Chemical Society,    San Francisco, March 2000
• The importance of micro-nutrients to mammalian cell productivity in serum-free cultures.  Bayer. San Francisco, February 2000           

  EDITOR:

• The Encyclopedia of Cell Technology: J.Wiley Biotechnology Series published 200
• Biotechnology Advances, Elsevier (1999-)
• Editorial Board: Biotechnology and Bioengineering (2003-)
• Editorial Board of Open Biotechnology Journals, Bentham Science publ. (2006-)
• Comprehensive Biotechnology. Volume 1 “Science behind biotechnology”, Elsevier (2008-)

PUBLICATIONS

BOOKS

• Castilho, L., Moraes, A., Augusto, E. & Butler, M. (Eds) 2008.  “Animal Cell Technology: from Biopharmaceuticals to Gene Therapy” 21 Chapters 518 pages  publ. Taylor & Francis.
• Butler, M. (Ed) 2007 Cell Culture and Upstream Processing. 250 pages publ Bios/ Taylor & Francis, Oxford
• Butler, M. 2004   Animal Cell Culture and Technology 2^nd edition 256 pages publ. Bios Scientific, Oxford.
• Butler,M. 1996. Animal Cell Culture and Technology 114 pages Oxford University Press
• Butler, M. and M.M. Dawson (eds). 1992. Cell Culture: Labfax 268 pages publ. Bios Scientific, Oxford.
• Butler, M. (Ed.) 1991. Mammalian Cell Biotechnology: A Practical Approach 245 pages; Oxford Univ. Press.
• Butler, M. 1987. "Animal Cell Technology: Principles and Products" 180 pages Open University Press.

REFEREED ARTICLES AND REVIEWS

Tharmalingam T, Sunley K, Spearman M, and Butler M. Enhanced Production of Human Recombinant Proteins from CHO cells Grown to High Densities in Macroporous Microcarriers.  Mol Biotechnol DOI 10.1007/s12033-011-9401-y

Maureen Spearman, Ben Dionne, and Michael Butler “The Role of Glycosylation in Therapeutic Antibodies”  In Antibody Expression and Production, Cell Engineering 7, M. Al-Rubeai (ed.), publ. Springer Science+Business Media B.V. 2011

Rodriguez J, Spearman M, Tharmalingam T, Sunley K, Lodewyks C, Huzel N and Butler M. High productivity of human recombinant beta-interferon from a low-temperature perfusion culture. J.Biotechnol.. 150: 509–5182010.

Sarah Murrell, Suh-Chin Wu and Michael Butler.  Dengue virus and the development of a vaccine.  Biotechnology Advances 29: 239-247, (2011)

David J. Harvey, Jaak Jaeken, Mike Butler, Alison J. Critchley, Pauline M. Rudd and Raymond A. Dwek “Fragmentation of negative ions from N-linked carbohydrates, Part 4. Fragmentation of complex glycans lacking substitution on the 6-antenna”    J of  Mass Spectrometry 45(5) 528-535:  2010

Durocher, Y and Butler, M  Expression Systems for therapeutic glycoprotein production.  Critical Opinions in Biotechnology 20(6) 700-7007: 2009    

Nikolic-Jaric,M., Romanuik, SF,,Ferrier,GA,_ Bridges,GE, Butler,M,.Sunley,K, Thomson,DJ and Freeman,MR  “Microwave Frequency Sensor for Detection of Biological Cells in  Microfluidic Channels” Biomicrofluidics 3, 034103 (2009); doi:10.1063/1.3187149

 

Butler, M.,Sparling, R.and  Court,D. “The energy metabolism of bacterial, fungal and animal cells used for industrial production.”  Encyclopedia of Industrial Biotechnology, Wiley publ. in press  2009.

 

Butler,M.  and  Perreault,H. “Approaches and Methods for determining Glycosylation”  Encyclopedia of Industrial Biotechnology, Wiley publ . in press  2009.

 

Sunley, K., Tharmalingam,T. and Butler,M.  (2008) CHO cells adapted to hypothermic growth produce high yields of recombinant beta-interferon.  Biotech Progress 24(4):898-906.

 

Tharmalingam, T.Sunley, K. and Butler,M.  (2008) High yields of monomeric recombinant beta-interferon from macroporous microcarrier cultures under hypothermic conditions. Biotech Progress 24(4): 832-838.

 

Butler, M.  “Mammalian cell lines and glycosylation: a case study.” In Biopharmaceuticals: post translational modifications  (Ed: G.Walsh) publ. Wiley VCH in press 2008.

 

 

 

Butler,M. “Post translational modification of  recombinant proteins” (Portuguese) for “Tecnologia do Cultivo de Celulas Animais: de Biofarmacos a Terapia Genetica” (Ed. E.Augusto) 2008 Editora Roca

 

Tharmalingam, T,. Ghebeh, H,. Wuerz, T and Butler,M. . (2008)  Pluronic enhances the robustness and reduces the cell attachment of mammalian cells.    Molecular Biotechnology 39(2), 167-77.

 

Amable, P and  Butler,M. Cell metabolism and its control in culture  In Castilho et al (Eds) “Animal Cell Technology: from Biopharmaceuticals to Gene Therapy”  Taylor & Francis 2008

 

Butler,M. “Post translational modification of  recombinant proteins”  In Castilho et al (Eds) “Animal Cell Technology: from Biopharmaceuticals to Gene Therapy”  Taylor & Francis 2008

 

Liu C-C, Lee S-C, Butler M, Wu S-C (2008) High genetic stability of dengue virus propagated in MRC-5 cells as compared to the virus propagated in vero cells.  PLoS ONE 3(3): e1810.

 

Chia-Chyi Liu, Wei-Cheng Lian, Michael Butler, Suh-Chin Wu.  (2007). High immunogenic enterovirus 71 strain and Its production using serum-free microcarrier Vero cell culture.  Vaccine. 25(1):19-24.

 

Majid, F.A,A. Butler M.and.Al-Rubeai M (2007) Glycosylation of an immunoglobulin produced from a murine hybridoma cell line: the effect of culture mode and the anti-apoptotic gene, bcl-2. Biotechnol Bioeng. 97(1) 156-169.

 

Butler, M. and Spearman, M. “Cell counting and viability measurements” in Animal Cell Biotechnology ­ Methods and Protocols (ed: Ralf Poertner) Humana Press March  2007 .

 

Spearman, M., Rodriguez, J. Huzel, N., Sunley, K. and Butler, M.(2007) Effect of Culture Conditions on Glycosylation of Recombinant beta-Interferon in CHO Cells. In "Animal Cell Technology: From target to market" (Smith, R. ed.) European Society for Animal Cell Technology 17, 200-203.

 Butler, M. (2006) Optimisation of the cellular metabolism of glycosylation for recombinant proteins produced by mammalian cell systems. Cytotechnology 50: 57-76 

 

Restelli, V, Wang, M-D, Huzel, N, Ethier, M, Perreault, H and Butler, M. (2006). The effect of dissolved oxygen on the production and the glycosylation profile of recombinant human erythropoietin produced from CHO cells. Biotech Bioeng 94 (3): 481-494.

 

Burgener, A., Coombs, K. and Butler, M. (2006). Intracellular ATP and total adenylate concentrations are critical predictors of reovirus productivity from Vero cells.   Biotech Bioeng 94 (4): 667-679.

 

Butler, M.  Animal cell cultures: recent achievements and perspectives in the production of biopharmaceuticals. (2005) Applied Microbiology and Biotechnology   68: 283-291.

 

Burgener, A. and Butler, M. “ Medium development” for “Cell Culture Technology for Pharmaceutical and Cell-based Therapies” (eds. Ozturk & Hu) pp 41-79 CRC Press 2005.

 

Butler, M. Biomanufacturing: the key to success in biotechnology (2005). Biotechnology Focus 8(3): 10-12.

 

Rodriguez, J., Spearman, M., Huzel, N. and Butler, M. (2005) Enhanced production of monomeric interferon-β by CHO cells through the control of culture conditions. Biotechnology Progress 21(1) 22-30.

 

Spearman, M., Rodriguez, J., Huzel, N. and Butler, M. (2004) Production and glycosylation of recombinant beta-interferon in suspension and Cytopore microcarrier cultures of CHO cells. Biotechnology Progress 21(1) 31-39

 

Butler, M., Quelhas, D., Critchley, A.J., Carchon, H., Hebestreit, H.F.,Hibbert, R.G., Vilarinho, L.,Teles, E., Matthijs, G., Schollen, Argibay, P., Harvey, D.J., Dwek, R.A., Jaeken, J. and Rudd, P.M. 2003 Detailed glycan analysis of serum glycoproteins of patients with congenital disorders of glycosylation indicates the specific enzyme defect and, coupled with proteomics, provides an insight into pathogenesis.    Glycobiology 13: 601-622.

 

Ethier,M., Saba, J.A., Spearman,M., Krokhin,O.,Butler,M.,Ens,W., Standing,K.G.and Perreault,H. 2003. Application of the StrOligo algorithm for the automated structure assignment of complex N-linked glycans from glycoproteins using tandem mass spectrometry. Rapid Communications in Mass Spectrometry 17 (24),: 2713-2720.

 

Saba, JA., Kunkel, J.P., Jan, D.CH., Ens, W.E., Standing, K.G., Butler, M., Jamieson, J.C. and Perreault, H. 2002 “A study of IgG glycosylation in monoclonal and polyclonal species by electrospray and matrix-assisted laser desorption/ ionization mass spectrometry” Anal Biochem. 305: 16-31.

Restelli,V. and Butler,M. 2002 “The effect of cell culture parameters on protein glycosylation”   Cell Engineering Vol 3: Glycosylation (Al-Rubeai ed.)   pp. 61-92 publ. Kluwer, Dordrecht.

Butler,M. 2002. “Genetic engineering of hybridomas.” In Encyclopedia of Physical Sciences and Technology. (ed. R.A.Meyers) Volume 7: 427-443 publ.Academic Press.

Yang,M. and Butler,M. 2002. Effects of ammonia and glucosamine on the heterogeneity of erythropoietin glycoforms. Biotechnology Progress. 18: 129-138.

Wang M-D, Yang, M., Huzel, N. and Butler, M. 2002 Erythropoietin production from CHO cells grown by continuous culture in a fluidized-bed bioreactor Biotech Bioeng 77:194-203.

Ghebeh, H., Gillis, J. and Butler, M. 2002. Measurement of the cell surface hydrophobicity of cultured mammalian cell lines. J. Biotechnol. 95: 39-48.

Barnabé, N., Butler, M. and Hasinoff,B.B. 2001 “The effect of the catalytic topoisomerase II inhibitor dexrazane (ICRF-187) on CC9C10 hybridoma viability and productivity” Cytotechnology 37: 107-117:

Burgener, A., Patrick, M., Coombs, K., Moffatt, D., Huzel, N. and Butler, M 2001. “The modification of a serum-free media formulation for the production of reovirus and the growth of Vero, MRC-5, MDCK and BHK cells” In "Animal Cell Technology: From target to market" (Lindner-Olsson, E, Chatzissavidou, N. and Lullau, E. eds.) European Society for Animal Cell Technology 17, 200-203.

Butler, M., Burgener, A., Patrick, M., Berry,M., Moffatt, D., Huzel, N., Barnabé,N. and Coombs,K. 2000. Application of a serum-free medium for the growth of Vero cells and the production of reovirus Biotech. Progress 16(5): 854-858.

Yang,M. and Butler,M. 2000. The effect of ammonia on the glycosylation of human recombinant erythropoietin in culture Biotech. Progress 16(5): 751-759.

Yang,M. and Butler,M. 2000. Enhanced erythropoietin heterogeneity in a CHO culture is caused by proteolytic degradation and can be eliminated by a high glutamine level. Cytotechnology 34 (1-2): 83-99.

Barnabé, N. and Butler, M. 2000The effect of glucose and glutamine on the intracellular nucleotide pool and oxygen uptake rate of a murine hybridoma. Cytotechnology 34 (1-2): 47-57.

Kunkel, J.P., Jan, D.C.H., Butler,M. and Jamieson, J.C. 2000. Comparisons of the glycosylation of a monoclonal antibody produced under nominally-identical cell culture conditions in two different bioreactors. Biotechnol. Progress 16 (3), 462-470.

Yang,M. and Butler,M. 2000. Effects of ammonia on CHO cell growth, erythropoietin production and glycosylation. Biotech. Bioeng. 68: 370-380.

Butler M., Kunkel J, Jan D., Huzel N. and Jamieson J.. (2000) The glycosylation of immunoglobulin (IgG) in bioreactors. Biotecnologia Aplicada , 17(3): 191.

Broadhurst, E.R. and Butler, M. 2000. The inhibitory effect of glutamate on the growth of a murine hybridoma is caused by competitive inhibition of the x^-_C transport system required for cystine utilization. Cytotechnology 32: 45-61.

Butler,M. 2000 "Equipment and laboratory design for cell culture" In: Encyclopedia of Cell Technology (Spier R.E. ed.) pp. 680-691 publ. J.Wiley, NY

Butler, M. 2000 "Measurement of cell viability " In: Encyclopedia of Cell Technology (Spier R.E. ed.) pp. 887-891 publ. J.WileyNY

Butler, M., Huzel, N., Barnabé, N., Gray, T. and Bajno, L. 1999. Linoleic acid improves the robustness of cells in agitated cultures. Cytotechnology 30 (1-3): 27-36.

Berry, J.M., Barnabé, N., Coombs,K. M. and Butler, M. 1999. Production of reovirus type-1 and type-3 from Vero cells grown on solid and macroporous microcarriers. Biotech. Bioeng. 62 (1): 12-19.

Butler, M. 1999. Cell counting and viability measurements. pp. 131-144 in Methods in Molecular Biology (ed. N.Jenkins). Humana Press, New Jersey.

Wang, M.D., Yang, M. Huzel N. and Butler, M. 1999. "Erythropoietin production from CHO cells grown in a fluidized-bed bioreactor with macroporous beads" In "Products from cells; cells as products" (Bernard, A, Griffiths, B., Noe, W. and Wurm, F. eds.) European Society for Animal Cell Technology 16, 307-309.

Christie, A. and Butler, M. 1999. The adaptation of BHK cells to a non-ammoniagenic glutamate-based culture medium. Biotech & Bioeng 64 (3): 298-309.

Butler,M., Sparling, R. and Xiao,X. 1999 "Energy Metabolism, Microbial and Animal Cells" In Encyclopedia of Bioprocess Technology: Fermentation, Biocatalysis, and Bioseparation (Ed. M. C. Flickinger and S. W. Drew) Vol. 2, pp 929 - 947.

Ghebeh,H., Handa-Corrigan,A. and Butler,M. 1998. Development of an assay to measure the surfactant, Pluronic F-68 in cell culture medium. Anal. Biochem. 262 (1): 39-44.

Kunkel, J.P., Jan, D.C.H., Jamieson, J.C. and Butler, M. 1998. Dissolved oxygen concentration in serum-free continuous culture affects N-linked glycosylation of a monoclonal antibody. J. Biotechnol. 62 (1); 55-71.

Barnabé,N. and Butler,M. 1998. The relationship between intracellular UDP-N-acetyl hexosamine nucleotide pools and monoclonal antibody production in a mouse hybridoma. J. Biotechnol. 60 (1-2): 67-80.

Butler,M., Huzel,N., Barnabé,N., Bajno,L and Gray,T. 1998 Intracellular fatty acid composition affects cell yield, energy metabolism and cell damage in agitated cultures. In "New developments and new applications in Animal Cell Technology" (Merten, O-W., Perrin, P. and Griffiths, B. eds.) European Society for Animal Cell Technology 15, 197-203.

Butler,M., Huzel,N. and Barnabé,N. 1997. Unsaturated fatty acids enhance cell yields and perturb the energy metabolism of an antibody-secreting hybridoma. Biochem J. 322, 615-623.

Jan,D.C.H., Petch, D., Huzel, N. and Butler, M. 1997.   The effect of dissolved oxygen on the metabolic profile of a murine hybridoma grown in serum-free medium in continuous culture. Biotech. Bioeng. 54 (2), 153-164.

Berry,J.M., Huebner,E. and Butler,M. 1997. Cell productivity is overestimated by the crystal violet nuclei counting technique. In Animal Cell Technology: From vaccines to genetic medicine. (Carrondo, J.T., Griffiths, B. and Moreira, J.L.P. eds.) European Society for Animal Cell Technology 14, 461-466.

Butler, M. and Huzel, N. 1997. Optimisation of the fatty acid composition of a hybridoma enhances Mab production and perturbs energy metabolism. In “Animal Cell Technology: From vaccines to genetic medicine” (Carrondo, J.T., Griffiths, B. And Moreira, J.L.P. eds.) European Society for Animal Cell Technology 14, 657-662.

Jan, D.C.H., Petch, D.A., Huzel, N. and Butler, M. 1997. The metabolic profile of a murine hybridoma grown in serum-free medium at various oxygen concentrations. In “Animal Cell Technology: From vaccines to genetic medicine” (Carrondo, J.T., Griffiths, B. And Moreira, J.L.P. eds.) European Society for Animal Cell Technology 14, 791-796.

Berry,J.M., Huebner,E. and Butler,M. 1996. The crystal violet nuclei staining technique leads to anomalous results in monitoring mammalian cell cultures. Cytotechnology 21 (1), 73-80.

Ng, Y-C., Berry, J.M. & Butler, M.1996. Optimisation of physical parameters for cell attachment and growth on macroporous microcarriers. Biotech. Bioeng 50 (6), 627-635.

Butler, M. and Chu,C.C. 1996. "Cell culture and biotechnology" In `Cell Biology' 2nd edition (eds. Smith, C.A. and Wood, E.J.) pp. 87-110 publ. Chapman & Hall, London .

Petch,D. and Butler,M. 1996. The effect of alternative carbohydrates on the growth and antibody production of a murine hybridoma. Applied Biochem. and Biotech. 59 (1): 93-104.

Butler,M. and Huzel,N. 1995. The effect of fatty acids on hybridoma cell growth and antibody productivity in serum-free cultures. J. Biotechnol. 39, 165-173.

Butler,M. and Huzel,N. 1995. The effect of unsaturated fatty acids on the growth, metabolism and productivity of a murine hybridoma. In "Animal Cell Technology: developments towards the 21st century" (Beuvery, E.C., Griffiths, J.B. and Zeijlemaker, W.P. eds.) European Society for Animal Cell Technology. 13, 125-129.

Christie,A. and Butler,M. 1994. Glutamine-based dipeptides are utilized in mammalian cell culture by extracellular hydrolysis catalyzed by a specific peptidase. J. Biotechnol. 37, 277-290.

Butler,M. and Christie,A. 1994. Adaptation of mammalian cells to non-ammoniagenic media. Cytotechnology 15, 87-94.

Barnabe,N. and Butler,M. 1994. Effect of temperature on nucleotide pools and monoclonal antibody production in a mouse hybridoma. Biotech. Bioeng. 44, 1235-1245.

Petch,D. and Butler,M. 1994. A profile of energy metabolism in a murine hybridoma: glucose and glutamine utilization. J.Cell Physiol. 161, 71-76.

Christie,A. and Butler,M. 1994. Growth and metabolism of a murine hybridoma in cultures containing glutamine-based dipeptides. Focus 16.1, 9-13.

Christie,A. and Butler,M. 1994. The effect of glutamine-containing dipeptides on the growth and productivity of a hybridoma. In "Animal Cell Technology: products of today, prospects for tomorrow" (Spier, R.E., Griffiths, J.B. and Berthold,W. eds.) European Society for Animal Cell Technology. 12, 164-166.

Fitzpatrick,L. Jenkins,H.A. and Butler,M. 1993. Glucose and glutamine metabolism of a murine B-lymphocyte hybridoma grown in batch culture. Applied Biochem. and Biotech. 43, 93-116.

Cole,C.R., Smith,C.A. and Butler,M. 1993.   Specific activities of glycosyltransferase enzymes vary with monoclonal antibody productivity in murine hybridomas. Biotech. Lett. 15(6) 553-558.

McDermott,R.H. and Butler,M. 1993. Uptake of glutamate, not glutamine synthetase, regulates adaptation of mammalian cells to glutamine-free medium. J. Cell Sci. 104(1) 51-58.

Jenkins, H.A., Butler, M. and Dickson, A.J. 1992. Characterization of the importance of glutamine metabolism to hybridoma cell growth and productivity. J. Biotechnol. 23, 167-182.

Butler, M. 1992. "Serum-free media for neuronal cell culture" pp. 55-75 In 'Cell Lines in Neurobiology: A practical approach' (Wood, J.N. ed). OxfordUniversity Press

Jenkins, H.A., L. Fitzpatrick, and M. Butler. 1992. Energy metabolism of murine hybridomas. In "Animal Cell Technology: Developments, processes and products" (Spier, R.E., Griffiths, J.B. and MacDonald,C. eds.) European Society for Animal Cell Technology. 11, 243-247.

Butler, M. and A. Barnett. 1991. "Cell culture and biotechnology" In `Molecular Biology and Biotechnology' (eds. Smith, C.A. and Wood, E.J.) pp. 213-234 Chapman & Hall, London.

Hassell, T., S. Gleave and M. Butler. 1991. Growth inhibition in animal cell culture: the effect of lactate and ammonia. Appl. Biochem. Biotech. 30(1), 29-41.

Butler, M. 1991. "The characteristics and growth of cultured cells" 1-25 In `Mammalian Cell Biotechnology: A practical approach' (Butler, M. ed). OxfordUniversity Press.

Butler, M., T. Hassell, C. Doyle, S. Gleave, and P. Jennings. 1991. The effect of metabolic by products on animal cells in culture. In "Production of Biologicals from Animal Cells in Culture" (Spier, R.E., Griffiths, J.B. and Meigner, B. eds.) European Society for Animal Cell Technology, 10, 226-228.

Thomas, R.H., H.A. Jenkins and M. Butler. 1991. Adaptation of anchorage-dependent cells to glutamine-free medium. In "Production of Biologicals from Animal Cells In Culture" (Spier, R.E., Griffiths, J.B. and Meigner, B. eds) European Society for Animal Cell Technology 10, 276-278.

Doyle, C. and M. Butler. 1990. The effect of pH on the toxicity of ammonia to a murine hybridoma. J. Biotechnol. 15, 91-100.

Hassell, T. and M. Butler. 1990. Adaptation to non-ammoniagenic medium and selective substrate feeding lead to enhanced yields in animal cell cultures. J. Cell Sci. 96, 501-508.

Butler, M. 1990. The use of animal cell and tissue culture in biotechnology. The Genetic Engineer and Biotechnologist 10, 13-15.

Butler, M. and H. Jenkins. 1989. Nutritional aspects of growth of animal cells in culture. J. Biotechnol. 12, 97-110.

Butler, M. 1988. A comparative review of microcarriers available for the growth of anchorage-dependent animal cells." pp. 284-303 In Animal Cell Biotechnology, vol. 3 (eds Griffiths, B. and Spier, R.E.) Academic Press.

Butler, M. 1988. "Processes with animal cell and tissue cultures" pp. 249-316 In Biotechnology: A comprehensive treatise, vol. 6b (eds Rehm, H.J. and Reed, G.) VCH Verlag.

Butler, M., T. Hassell, and A. Rowley. 1987. "The use of microcarriers in the culture of anchorage-dependent animal cells" pp. 64-74 In Plant and Animal Cells: process possibilities (eds. Webb, C. and Mavituna, F.) Ellis Horwood.

Butler, M. 1987. Growth limitations in microcarrier cultures. Advances in Biochemical Engineering 34, 57-84.

Sayer, T., M. Butler, and A. MacLeod. 1987. The attachment of MDCK cells in three types of microcarriers in different serum-free media In "Modern Approaches to Animal Cell Technology" (Spier, R.E. and Griffiths, J.B. eds.) European Society of Animal Cell Technology 9, 264-279.

Hassell, T., I. Allen, A. Rowley, and M. Butler. 1987. The use of a glutamine-free media for the growth of three cell lines in microcarrier culture. In Modern Approaches to Animal Cell Technology (Spier, R.E. & Griffiths, J.B. eds.) European Society of Animal Cell Technology. 9, 245-263.

Butler, M. 1987. Animal Cell Biotechnology vols 1 & 2, Spier & Griffiths (eds.) Book review. Vaccine 5(4) 323 

Butler, M. 1986. "Serum-free media" pp. 91-108 In Mammalian Cell Technology (ed. W.G. Thilly) Butterworths.

Butler, M. 1985. "Growth limitations in high density microcarrier cultures" Developments in Biological Standardization. ( European Society for Animal Cell Technology) 60: 269-280.

Butler, M. and R.E. Spier. 1984. The effects of glutamine utilisation and ammonia production on the growth of BHK cells in microcarrier cultures. J. Biotechnol. 1: 187-196.

Butler, M. 1983. Biotechnology - making micro-organisms work for man. Esso magazine 127: 16-19.

Butler, M., T. Imamura, J. Thomas, and W.G. Thilly. 1983. High yields from microcarrier cultures by medium perfusion. J. Cell Sci. 61: 351-363.

Butler, M., and W.G. Thilly. 1982. MDCK microcarrier cultures: Seeding density effects and amino acid utilization. In Vitro 18: 213-219.

Butler, M., A.E.J. Haskew, and M.M. Young. 1980. Copper tolerance in the green alga, Chlorella vulgaris. Plant, Cell and Environment 3, 119-126.

Hall, A., A.H. Fielding, and M. Butler. 1979. Mechanism of copper tolerance in the marine fouling alga, Ectocarpus siliculosus - evidence for an exclusion mechanism. Marine Biology 54: 195-199.

Butler, M. and J.B. Capindale. 1975. Assimilation of citric acid and adipic acid by the blue-green alga, Anabaena variabilis. Can. J. Microbiol. 21: 1372-1378.

Butler, M., A. Darbre and H.R.V. Arnstein. 1975. Amino acids attached to transfer ribonucleic acid in vivo. Biochem. J. 150: 419-432.

Butler, M., and A. Darbre. 1974. Determination of amino acids by gas-liquid chromatography with the nitrogen-sensitive thermionic detector. J. Chromatogr. 101: 51-56.

Butler, M., A. Darbre, and H.R.V. Arnstein. 1973. Analysis of amino acids attached to transfer ribonucleic acid by means of gas-liquid chromatography. Biochem. Soc. Trans. 1: 610.