SEMINAR

Evolving Proteins: Bio-inspired Chemistry

Abstract
Protein engineering is a rapidly growing area of research that can facilitate a great many practical applicarions. Engineering on the molecular level implies protein modification that can be made in a variety of ways. We use a bio-inspired approach: directed evolution. This approach mirrors what happens in nature; mutant libraries are created and desirable traits selected for. This technology can be used to alter the substrate specificity of an enzyme as well as enhance it stability and improve its solubility (1) – all useful processes if we are to create practical catalysts.

In addition to producing enzymes with enhanced catalytic properties, directed evolution offers a new and powerful tool with which to probe enzyme mechanics. Mutants with enhanced catalytic properties can be probed with structural tools and spectroscopic techniques to give a better understanding of how they function. This information can then be used to engineer another generation of enzymes (2).

References
(1) Liu,J-W., Yan Boucher, Y., Stokes. HW, and Ollis, DL. Improving protein solubility: the use of the Escherichia coli dihydrofolate reductase gene as a fusion reporter. Protein Expression and Purification (2006) 47(1) 258-263.

(2) Porter, J.L., Boon, P.L.S., Murray, T.P., Huber, T.L. Collyer, C.A. and Ollis, D.L. Directed evolution of new and improved enzyme functions using and evolutionary intermediate and multi-directional search. ACS Chemical Biology (2015) 10(2):611-21.

BIOGRAPHY

2005-present: Professor, Protein Crystallography and Engineering Lab, RSC
1992 – 2006: Senior Fellow, Protein Crystallography and Engineering Lab, RSC
1991-1991: Associate Professor (with Tenure) Northwestern University, U.S.A.
1986-1991: Assistant Professor, Northwestern University, U.S.A.Postdoctoral Research 1980-1985: post-Doctoral (with Steitz) Yale University, USA

Research Interests

X-ray crystallography: protein structure determination, protein structure and function studies: of replication proteins, proteins involved in nitrogen uptake in bacteria and receptor structure and function. Protein engineering with an emphasis on directed evolution.

Selected publications

Ollis, D. L., Brick, P., Hamelin, R., Huong, N. G. and Steitz, T. A. (1985) Structure of the Large Fragment of Escherichia coli DNA Polymerase I Complexed with dTMP. Nature, 313, 762-766.

Ollis, D. L., Kline, C. and Steitz, T. A. (1985) Domain of E. coli DNA Polymerase I Shows Sequence Homology with T7 DNA Polymerase. Nature, 313, 818-819.

Ollis, D. L., Cheah, E., Cygler, M., Dijkstra, B., Frolow, F., Franken, S. M., Harel, M., Remington, S. J., Silman, I., Schrag, J., Sussman, J. L., Verschueren, K. H. G. and Goldman, A. (1992) The alpha/beta Hydrolase Fold. Protein Engineering, 5, 197-211.

Jaggi, R., van Heeswijk, W. C., Westerhoff, H. V., Ollis, D. L., and Vasudevan, S. G. (1997) The two opposing activities of adenylyl transferase reside in distinct homologous domains, with intramolecular signal transduction. The EMBO Journal, 16, 5562-5571.

Carr, P. D., Gustin, S. E., Church, A. P., Murphy, J. M., Ford, S. C., Mann, D. A., Woltring, D. M., Walker, I., Ollis, D. L. and Young, I. G. (2001) Structure of the complete extracellular domain of the common  subunit of the human GM-CSF, IL-3 and IL-5 receptors reveals a novel dimer configuration. Cell, 104, 291-300.

Yang, H., Carr, P.D., Yu-McLoughlin, S., Liu, J.W., Horne, I. Qui, X., Jeffries, C.M.J., Russell, R.J., Oakeshott, J.G. and Ollis, D.L. (2003) Evolution of an organophosphate-degrading enzyme: a comparison of natural and directed evolution. Protein engineering 16(2) 135-145.