Paul Dalby
Reader in Biochemical Engineering
Graduate Admissions Tutor
Phone:+44 (0)20 7679 2962
Fax: +44 (0)20 7383 2348
p.dalby@ucl.ac.uk
Education
PhD MRC Centre for Protein Engineering, Cambridge University (1997)
MA (Hons) (Cantab) Natural Sciences, Cambridge University, Gonville & Caius College (1994)
Professional Appointments, Honours and Awards
Chair of the RSC Biotechnology Group Committee (2008-present). Member since 2003
Member of the Royal Society of Chemistry (2005-present)
Member of the Protein Society (2006–present)
Associate Member of the Institute of Chemical Engineers (2003-present)
Evonik European Science-to-Business Award (2008)
Postdoctoral fellowship, School of Medicine , University of Pennsylvania (1998-2000)
Gonville & Caius College Dunlop Scholarship (1994-1997)
Gonville & Caius College Senior Scholarship (1993-1994)
James Arthur Ramsay Prize in Chemistry & Biology (1993)
Editorial Board Member for Open Biotechnology Journal (2007-present)
Editorial Advisory Board for Recent Patents in Biotechnology (2006-present)
Research Interests
Paul Dalby leads research at UCL on the application of protein engineering and biophysics in the fields of biocatalysis and biopharmaceutical manufacturing.
As part of the Bioconversion-Chemistry-Engineering Interface (BiCE) Programme, he has applied a combination of directed evolution and bioinformatics to improve the activity, substrate specificity and enantioselectivityof biocatalytic enzymes under biotransformation process conditions. Closely collaborating with Professor John Ward (Biochemistry and Molecular Biology) and Dr Helen Hailes (Chemistry), novel enzymes have been engineered which produce complex chiral molecules with reversed enantioselectivities to those observed in the parent enzyme. The BiCE programme, led by Prof Gary Lye, involves a multidisciplinary team of researchers from three UCL faculties, and aims to establish novel techniques that speed the development of the next generation of complex pharmaceuticals. It is supported by a group of 13 leading national and international companies who comprise the BiCE Industrial Steering Group.
A major focus of Paul’s work is to establish biophysical techniques that can be used to better understand the interactions between proteins, additives and process conditions for protein refolding from inclusion bodies, and for liquid or freeze-dried formulations of biopharmaceuticals. Protein inclusion body refolding studies have included collaborations with Prof Howard Chase at Cambridge University, and with Prof Nigel Titchener-Hooker, while freeze-drying work currently involves a collaboration with Dr Paul Matejtschuk at NIBSC. He has developed novel microplate-based screening techniques for protein stability, protein refolding, and enzyme activity that will enable the rapid design of enhanced bioprocesses, formulations and delivery of therapeutic proteins. In BBSRC (BRIC) supported research he has translated these techniques to an even more high-throughput and less sample intensive microfluidic device. Paul also has collaborations with Dirk Werling at the Royal Veterinary College, Hatfield, UK, to develop novel protein conjugate vaccines for animal diseases, and Professor Stephen Perkins at UCL to analyse the solution conformations of antibody-based therapeutics and their aggregation mechanisms.
Funding for the above research has come from the UK BBSRC, EPSRC, the TSB Technology Programme and a range of company collaborators.
Teaching and Training Activities
Paul’s current teaching activities span all years of the various degree course programmes operated by the Department. These include coordination of the Introduction to Biochemical Engineering and the final year research project modules, as well as the post-experience MBI® training module in Biocatalysis and the PhD/EngD induction training course. He also teaches aspects of biochemistry, enzyme kinetics, biocatalysis and protein engineering at all levels from undergraduate to Masters level students. In particular he manages teaching at the interface between biochemistry and biochemical engineering.
Paul also has administrative roles as Departmental Postgraduate Research Admissions Tutor, and Departmental undergraduate staff-student consultative committee Chair.
Selected Publications
*If you would like further information on any of these publications or news of related research, please contact p.dalby@ucl.ac.uk
Cázares, A., Galman, J.L., Crago, L.G., Smith, M.E.B., Strattford, J., Ríos-Solís, L., Lye, G.J., Dalby, P.A., Hailes, H.C. (2010) Organic & Biomolecular Chemistry. Non-alpha-hydroxylated aldehydes with evolved transketolase enzymes. doi: 10.1039/b924144b Cover of issue 8(6) 2010, March 21.
Hailes, H.C., Dalby, P.A., Lye, G.J., Baganz, F., Micheletti, M., Szita, N., Ward, J.M. (2010) Current Organic Chemistry. a, a'-Dihydroxyketones and 2-Amino-1, 3-diols: Synthetic and Process Strategies using Biocatalysts. In press.
Smith, M.E.B., Chen, B.H., Hibbert, E.G., Kaulmann, U., Smithies, K., Galman, J.L., Baganz, F., Dalby, P.A., Hailes, H.C., Lye, G.J., Ward, J.M., Woodley, J.M., Micheletti, M. (2009) Org. Proc. Res. Dev. 14(1), 99-107. A Multi-Disciplinary Approach Toward the Rapid and Preparative Scale Biocatalytic Synthesis of Chiral Amino Alcohols: A Concise Transketolase / w- Transaminase-Mediated Synthesis of (2S, 3S)-2-Aminopentane-1,3-diol. (10.1021/op900190y)
Grant, Y., Matejtschuk, P., Dalby, P.A. 2009. Rapid optimisation of protein freeze-drying formulations using ultra scale-down and factorial design of experiment in microplates. doi:10.1002/bit.22448
Paramesvaran, J., Hibbert, E.G., Russell, A.J., Dalby, P.A. 2009. Distributions of enzyme residues yielding mutants with improved substrate specificities from two different directed evolution strategies. Protein Engineering Design and Selection. 22(7), 401-411.
Mannall, G.J., Myers, J.P., Liddell, J., Titchener-Hooker, N.J., Dalby, P.A. 2009. Ultra scale-down of protein refold screening in microwells: Challenges, solutions and application. Biotech. Bioeng. 103(2), 329-340.
Smith, M.E.B., Hibbert, E.G., Jones, A.B., Dalby, P.A., Hailes, H.C. 2008. Enhancing and reversing the enantioselectivity of E. coli transketolase via single point mutations. Adv Syn Catal. 350, 2631-2638.
Chen, B.H., Hibbert, E.G., Dalby, P.A. and Woodley, J.M. 2008. A new approach to bioconversion reaction kinetic parameter identification. AIChE J. 58, 2155-2163.
Hibbert, E.G., Senussi, T., Smith, M.E.B., Costelloe, S.J., Ward, J.M., Hailes, H.C., Dalby, P.A. 2008. Directed evolutions of transketolase substrate specificity towards an aliphatic aldehyde. J. Biotechnol. 134, 240-245.
Costelloe, S.J., Ward, J.M., and Dalby, P.A. 2008. Evolution of the TPP-dependent enzyme family. J. Molecular Evolution. 66, 36-49. doi: 10.1007/s00239-007-9056-2
Aucamp, J.P., Martinez-Torres, R.J., Hibbert, E.G. and Dalby, P.A. 2008. A microplate-based evaluation of complex denaturation pathways: Structural stability of E. coli transketolase.Biotech. Bioeng. 99, 1303-1310. doi:10.1002/bit.21705
Hibbert, E.G., Senussi, T., Costelloe, S.J., Lei, W., Smith, M.E.B., Ward, J.M., Hailes, H.C., and Dalby, P.A. 2007. Directed evolution of transketolase activity on non-phosphorylated substrates. Journal of Biotechnology131, 425-432. doi:10.1016/j.jbiotec.2007.07.949
Martinez-Torres, R.J., Aucamp, J.P., George, R. and Dalby, P.A. 2007. Structural stability of E. coli transketolase to urea denaturation. Enzyme Microb. technol.41, 653-662. doi:10.1016/j.enzmictec.2007.05.019
Mannall, G. J., Titchener-Hooker, N. J. and Dalby, P. A. 2007. Factors affecting protein refolding yields in a fed-batch and batch-refolding system. Biotech. Bioeng. 97 , 1523-1534.
doi: 10.1002/bit.21377
Ingram, C. U., Bommer, M., Smith, M. E. B., Dalby, P. A., Ward, J. M., Hailes, H.C., Lye, G. J. 2007. One-pot synthesis of amino-alcohols using a de-novo transketolase and b -alanine:pyruvate transaminase pathway in Escherichia coli.Biotech. Bioeng.96, 559-569. doi: 10.1002/bit.21125
Chen, B. H., Sayar, A., Kaulmann, U., Dalby, P. A., Ward, J. M. and Woodley, J. M. 2006. Reaction modelling and simulation to assess the integrated use of transketolase and ω-transaminase for the synthesis of an aminotriol. Biocatal. Biotrans.24: 449-457. doi:10.1080/10242420601068668
Mannall, G. J., Titchener-Hooker, N. J., Chase, H. A. and Dalby, P. A. 2006. A critical assessment of the impact of mixing on dilution refolding. Biotech. Bioeng.93: 955-963. doi: 10.1002/bit.20796
Smith, M. E. B., Smithies, K., Senussi, T., Dalby, P. A. and Hailes, H. C. 2006. The First Mimetic of the Transketolase Reaction. Eur J. Org. Chem. 1121-1123. doi: 10.1002/ejoc.200500986
Aucamp, J.P., Cosme, A.M., Lye, G.J., Dalby, P.A. 2005. High-throughput measurement of protein stability in microtiter plates. Biotech Bioeng., 89 (5): 599-607. doi: 10.1002/bit.20397
Dalby, P.A. 2003. Optimizing enzyme function by directed evolution. Curr. Opin. Struct. Biol., 13 (4): 500-505. doi:10.1016/S0959-440X(03)00101-5
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