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Burckhard Seelig

Associate Professor

Expertise:

Lab Website

Research Description

Our research group implements Darwinian molecular evolution in a test tube to:

(A)  Generate novel proteins for synthetic biology and biomedical applications

(B)  Study the origin and evolution of functional proteins

(C)  Investigate the history of the genetic code

We apply methods of in vitro and in vivo selection and evolution to generate de novo proteins with custom-made properties. We also tailor existing enzymes to a variety of useful applications.  We established a general method to design novel enzymes from scratch - enzymes that have not been found in nature.  This method is based on the mRNA display technology, which enables us to search for new enzymes in libraries of trillions of protein variants in a single experiment. These library complexities are well beyond the limits of conventional screening technologies.

Our projects comprise both applied and basic research.  One objective of our work is to create enzymes as 'designer catalysts' to harness the power of enzymes for the synthesis of chemicals and pharmaceuticals, and for biomedical applications.  In addition, we study our new proteins in detail to help elucidate fundamental principles of biocatalysis, protein evolution and the origin of the genetic code.

The research carried out in our lab combines a number of different disciplines, including molecular biology, biochemistry, organic chemistry and protein engineering.


Recent Publications

In the News: (Research Highlight - NASA) (Science Highlight - Stanford Synchrotron) (CBS Highlight) (SciTechDaily) (ScienceDaily) (Minnesota Daily) (reddit) (most read article of Nature Chem. Biol. !)

Newton, M. S., Morrone, D., Lee, K.-H. & Seelig, B. (2018) Genetic code evolution investigated through synthesis and characterisation of proteins from reduced alphabet libraries. ChemBioChem. 2018 (PDF)

Newton, M. S., Cabezas, Y. & Seelig, B.: Advantages of mRNA display. Meth. Mol. Biol. 2017 (in press)

Morelli, A., Cabezas, Y., Mills, L. J. & Seelig, B.: Extensive libraries of gene truncation variants generated by in vitro transposition. Nucleic Acids Res. 2017 (doi: 10.1093/nar/gkx030) (PDF)

Lane M. D., & Seelig, B.: Highly efficient recombinant production and purification of streptococcal cysteine protease streptopain with increased enzymatic activity. Protein Expr. Purif. 2016 (121) 66-72. (PDF) (Pubmed)

Lane M. D., Seelig B.: Advances in the directed evolution of proteins. Curr. Opin. Chem. Biol. 2014 (22) 129-136. (PDF) (Pubmed)

Morelli, A., Haugner III, J. C. & Seelig, B.: Thermostable artificial enzyme isolated by in vitro selection. PLOS ONE 2014 9(11): e112028 (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) (NCB website)
In the News: (Research Highlight - NASA) (Science Highlight - Stanford Synchrotron) (CBS Highlight) (SciTechDaily) (ScienceDaily) (Minnesota Daily) (reddit) (most read article of Nature Chem. Biol.!)

Golynskiy, M. V., Haugner III, J. C. & Seelig, B.: Highly diverse protein library based on the ubiquitous (β/α)8 enzyme fold yields well-structured proteins through in vitro folding selection. ChemBioChem 2013 (14) 1553-1563. (PDF)

Haugner III, J. C. & Seelig, B.: Universal labeling of 5’-triphosphate RNAs by artificial RNA ligase enzyme with broad substrate specificity. Chem. Commun. 2013 (49) 7322-7324. (PDF) (Recommended by F1000Prime)

Golynskiy, M. V., Haugner III, J. C., Morelli, A., Morrone, D., & Seelig, B.: In vitro evolution of enzymes. Meth. Mol. Biol. 2013 (978) 73-92. (PDF) (Pubmed)

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. (PDF)(Pubmed)

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.) (Chemical & Engineering News)

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)

P:
(612) 626-6281
E:

seelig@umn.edu

358A Gortner
1479 Gortner Avenue
St. Paul, MN 55108