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UCL Department of Biochemical Engineering

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Prof Paul Dalby

Prof Paul Dalby

Professor of Biochemical Engineering and Biotechnology

Dept of Biochemical Engineering

Faculty of Engineering Science

Joined UCL
1st Feb 2000

Research summary

Prof Paul Dalby is Co-Director of the EPSRC Future Targeted Healthcare Manufacturing Hub, Director of the associated EPSRC Centre for Doctoral Training, and a Fellow of the Royal Society of Chemistry.  His research focuses on routes to improve the stability and activity of biocatalytic enzymes and therapeutic proteins, for ease of manufacture, formulation and delivery to patients.  His work combines computationally-guided protein engineering and formulation, with biophysical characterisations, to understand the factors that influence protein stability, and then feeding back to inform the protein engineering strategies.  

Paul has pioneered the use of smart directed evolution libraries guided by protein structure analysis, substrate docking in silico, and bioinformatics. He has used this to improve the stability, activity, substrate range and enantioselectivity of a range of biocatalytic enzymes. Collaborating with Professor John Ward (Biochemical Engineering) 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. He has also pioneered (and patented) the concept of substrate walking for iteratively evolving an enzyme towards acceptance of progressively more distant substrates.

A major focus of Paul's work is to elucidate aggregation mechanisms in therapeutic protein formulations, in both the liquid and freeze-dried states.  He has established automated techniques to formulate proteins, and to evaluate their stability in response to excipients, both conformationally, and kinetically. He also collaborates extensively with Dr Paul Matejtschuk (NIBSC), and Prof Stephen Perkins (UCL) to achieve these aims. He is also Co-Director of the EPSRC Future Targeted Healthcare Manufacturing Hub, which in partnership with nearly 40 UK companies, aims to tackle the challenges emerging in the manufacture of increasingly stratified protein therapies, and personalised (precision) cell therapies such as CAR-T.  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 recent BBSRC (BRIC) supported research, in collaboration with the London Centre for Nanotechnology, he established these techniques within an even more high-throughput and less sample intensive microfluidic device, which also enabled optical heating to be coupled to optical interrogation of label-free samples.

Funding for the above research has come from the UK BBSRC, EPSRC, the TSB Technology Programme and a range of company collaborators.

Since July 2008 Paul has been Chair of the Royal Society of Chemistry's Biotechnology Subject Group which aims to engage academia, industry and the public in debate and scientific discussion on advances in Biotechnology. He received the Evonik European Science-to-Business Award in November 2008 for his work on engineering enzyme routes for the production of chiral intermediates.

Teaching summary

Paul's current teaching activities span all years of the various degree course programmes operated by the Department. He coordinates several modules including Protein Biochemistry and Biophysics for Engineers (Yr2 UG), Chemistry for Biochemical Engineers (Yr3 UG), Research Projects (Yr4 UG), and the post-experience MBI training module in Biocatalysis. He also teaches aspects of protein biochemistry, formulation, enzyme kinetics, biocatalysis and protein engineering, on a range of other modules for undergraduate and Masters level students. 

Paul also has a key administrative role as Director of the EPSRC Centre for Doctoral Training in Emergent Macromolecular Therapies.

Education

University of Cambridge
PhD, Biological Chemistry | 1997
University of Cambridge
MA, Natural Sciences | 1994
University of Cambridge
BA Hons, Natural Sciences | 1993

Biography

Paul Dalby is a Professor in Biochemical Engineering and Biotechnology at University College London, where he has been a principle investigator since April 2000. His protein engineering research aims to address key challenges in understanding protein formulation and aggregation, as well as to generate novel enzyme biocatalysts.

He graduated with a Natural Sciences degree from the University of Cambridge and received his PhD in 1998, also from the University of Cambridge, for work on protein engineering and protein folding under the guidance of Sir Prof Alan Fersht. He then undertook a Postdoctoral research fellowship at the University of Philadelphia, with Bill DeGrado.  Paul Dalby leads research at UCL on the application of protein engineering and biophysics in the fields of biocatalysis and biopharmaceutical manufacturing and formulation. 

Publications