Division Head: Synthetic Biology and Biotechnology
Our research focuses on implementing Darwinian evolution in a test tube to generate novel proteins with custom-made properties. We are interested in applying methods of in vitro selection and evolution to the generation of de novo enzymes as well as to tailoring existing enzymes to a wide variety of useful properties. We have established a general method to generate novel protein enzymes from scratch – enzymes that have not been found in nature. Our method employs the mRNA display technology, which generates libraries of proteins that are covalently linked to their coding mRNA. This stable connection between genotype and phenotype allows for the selection of proteins from large libraries with complexities well beyond the limits of conventional screening technologies. This method enables us to search for new enzymes in libraries of trillions of protein variants in a single experiment.
One objective of our research is to create enzymes as ‘designer catalysts’ because there is considerable interest in harnessing the power of enzymes for the synthesis of chemicals and pharmaceuticals and for the conversion of biomass. We are also studying our new enzymes in detail and evolve them further to help elucidate basic principles of biocatalysis and protein evolution.
The research carried out in our lab combines a number of different disciplines, including molecular biology, biochemistry, organic chemistry and protein engineering.
In the News: (Research Highlight - NASA) (Science Highlight - Stanford Synchrotron) (CBS Highlight) (SciTechDaily) (ScienceDaily) (Minnesota Daily) (reddit) (most read article of Nature Chem. Biol. !)
Morelli, A., Haugner III, J. C. & Seelig, B.: Thermostable artificial enzyme isolated by in vitro selection. PLOS ONE 2014 (in press). (PDF)
Chao, F.-A., Morelli, A., Haugner III, J. C., Churchfield, L., Hagmann, L. N., Shi, L., Masterson, L. R., Sarangi, R., Veglia, G. & Seelig, B.: Structure and dynamics of a primordial catalytic fold generated by in vitro evolution. Nature Chem. Biol. 2013 (9) 81-83. (PDF)
Traaseth, N. J., Chao, F.-A., Masterson, L. R., Mangia, S., Garwood, M., Michaeli, S., Seelig, B., Veglia, G.: Heteronuclear Adiabatic Relaxation Dispersion (HARD) for Quantitative Analysis of Conformational Dynamics in Proteins. J. Magn. Reson. 2012 (219) 75-82. (Pubmed) (PDF)
Seelig, B.: mRNA display for the selection and evolution of enzymes from in vitro-translated protein libraries. Nature Protocols. 2011 (6) 540-552. (PDF)
Golynskiy, M. V. & Seelig, B.*: De novo enzymes – from computational design to mRNA Display. Trends Biotechnol. 2010 (27) 340-345. (On the Cover & PDF)
Seelig, B.: An autocatalytic network for ribozyme self-construction. Nature Chem. Biol. 2008 (4) 654-655. (News & Views)
Seelig, B. & Szostak, J.W.: Selection and evolution of enzymes from a partially randomized non-catalytic scaffold. Nature, 2007 (44) 828-831. (PDF) (Supplementary Information) (News & Views in Nature) (Spotlight in ACS Chem. Biol.) (Highlight in Nature Chem. Biol.)
Keiper, S., Bebenroth, D., Seelig, B., Westhof, E. & Jäschke, A.: An architecture of a Diels-Alder ribozyme with a preformed catalytic pocket. Chem. Biol. 2004 (11) 1217-1227. (PDF)
Keefe, A.D., Wilson, D.S., Seelig, B. & Szostak, J.W.: One-step purification of recombinant proteins using a nanomolar-affinity streptavidin-binding peptide, the SBP-tag. Protein Expr. Purif. 2001 (23) 440-446. (PDF)
Jäschke, A. & Seelig, B.: Evolution of DNA/RNA as catalysts for chemical reaction. Curr. Opin. Chem. Biol. 2000 (4) 257-262. (PDF)
Seelig, B., Keiper, S., Stuhlmann, F. & Jäschke, A.: Enantioselective ribozyme catalysis of a bimolecular cycloaddition reaction. Angew. Chem. Int. Ed. 2000 (39) 4576-4579. (PDF)
Sengle, G., Jenne, A., Arora, P. S., Seelig, B., Nowick, J. S., Jäschke, A. & Famulok, M.: Synthesis, incorporation efficiency, and stability of disulfide bridged functional groups at RNA 5'-Ends. Bioorg. Med. Chem. 2000 (8) 1317-1329. (PDF)
Seelig, B. & Jäschke, A.: Ternary conjugates of guanosine monophosphate as initiator nucleotides for the enzymatic synthesis of 5'-modified RNAs. Bioconjugate Chem. 1999 (10) 371-378. (PDF)
Seelig, B. & Jäschke, A.: A small catalytic RNA motif with Diels-Alderase activity. Chem. Biol. 1999 (6) 167-176. (PDF)
Seelig, B. & Jäschke, A.: Site-specific modification of enzymatically synthesized RNA: transcription initiation and Diels-Alder reaction.Tetrahedron Lett. 1997 (38) 7729-7732. (PDF)