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.

Lee, K. H., Distefano, M.D. & Seelig, B. (2023) Facile immobilization of pyridoxal 5′-phosphate using p-diazobenzoyl derivatized Sepharose 4B. Results Chem. PMID: (PDF) (Pubmed)

Zhu, B., Du, Z., Dai, Y., Kitaguchi, T., Behrens, S. & Seelig, B. (2023) Nanodroplet-based reagent delivery into water-in-fluorinated-oil droplets. Biosensors PMID: (PDF) (Pubmed)

Medina-Carmona, E., Gutierrez-Rus, L., Manssour-Triedo, F., Newton, M. S., Gamiz-Arco, G., Mota, A. J., Cuerva, J. M., Andrés-León, E., Ortega-Roldan, J. L., Seelig, B., Ibarra-Molero, B., Sanchez-Ruiz, J. M. (2023) Cell survival enabled by leakage of a labile metabolic intermediate. Mol. Biol. Evol. PMID: 36788592 (PDF) (Pubmed)

Tong, C. L. Kanwar, N, Morrone, D., & Seelig, B. (2022) Nature-inspired engineering of an artificial ligase enzyme by domain fusion. Nucleic Acids Res. (19) 11175. PMID: 36243966 (PDF) (Pubmed)

Kanwar, N., Blanco, C., Chen, I. A. & Seelig, B. PacBio sequencing output increased 5-fold through uniform and directional concatenation. Sci. Rep. 2021 (11) 18065 PMID: 34508117 (PDF) (Pubmed) In the News: (genomeweb)

Kanwar, N., Blanco, C., Chen, I. A. & Seelig, B. PacBio sequencing output increased 5-fold through uniform and directional concatenation. Sci. Rep. 2021 In press

Gamiz-Arco, G., Gutierrez-Rus, L.I., Risso, V.A., Ibarra-Molero, B., Hoshino, Y., Petrovic, D., Justicia, J., Cuerva, J.M., Romero-Rivera, A., Seelig, B., Gavira, J.A., Kamerlin, S.C.L., Gaucher, E.A., Sanchez-Ruiz, J.M. Novel heme-binding enables allosteric modulation in an ancient TIM-barrel glycosidase. Nature Commun. 2021 PMID (PDF) (Pubmed) In the News: (Human Frontier Science Program)

Tong, C. L., Lee, K.-H. &  Seelig B. De novo proteins from random sequences through in vitro evolution. Curr. Opin. Struct. Biol. 2021 (68), 129-134. PMID: (PDF)

Newton, M. S., Cabezas-Perusse, Y., Tong, C. L. & Seelig, B. In vitro selection of peptides and proteins - advantages of mRNA display. ACS Synth. Biol. 2020 (9), 181-190. PMID: 31891492 (PDF) (Pubmed)

Blanco, C., Verbanic, S., Seelig, B. & Chen, I. EasyDIVER: a pipeline for assembling and counting high throughput sequencing data from in vitro evolution of nucleic acids or peptides. Bioinformatics. J. Mol. Evol. 2020 (88), 477-481. PMID: 32529275 (PDF) (Pubmed)

Blanco, C., Verbanic, S., Seelig, B. & Chen, I. High throughput sequencing of in vitro selections for proteins using mRNA display. Phys. Chem. Chem. Phys. 2020 PMID: 31967131 (PDF) (Pubmed)

Newton, M. S., Morrone, D., Lee, K.-H. & Seelig, B. Genetic code evolution investigated through synthesis and characterisation of proteins from reduced alphabet libraries. ChemBioChem. 2019 (20) 846-856. (PDF) (Pubmed)

Shan, Q., Baltes, N. J., Atkins, P., Kirkland, E. R., Zhang, Y., Baller, J. A., Lowder, L. G., Malzahn, A. A., Haugner, J. C., Seelig, B., Voytas, D. F., Qi, Y. ZFN, TALEN and CRISPR-Cas9 mediated homology directed gene insertion in Arabidopsis: a disconnect between somatic and germinal cells. J. Genet. Genomics. 2018 (18) 30173-5. PMID 30598393 (PDF) (Pubmed)

Seelig, B. Multifunctional enzymes from reduced genomes - model proteins for simple primordial metabolism Molecular Microbiol. 2017 (105), 505-7. PMID 8665040 (PDF) (Pubmed)

Morelli, A., Cabezas, Y., Mills, L. J. & Seelig, B.: Extensive libraries of gene truncation variants generated by in vitro transposition. Nucleic Acids Res. 2017 (45) e78 (PDF) (Pubmed)

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) (Pubmed)

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: (ACS Cent Sci) (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) (Pubmed)

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) (Pubmed)

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)
In the News: (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) (Paper was top 5 downloaded article for the journal in 2002.)

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)

Ph.D. in Biochemistry, Freie Universität Berlin, Germany, 1999

Postdoctoral Fellow, Harvard University