Justin Siegel, Ph.D.
The primary thrust of my research is to develop new tools and the knowledge necessary to rapidly and reliably discover novel enzyme catalysts. The projects selected have a synergy between tool & knowledge development, education, and societal impact. Research within the lab generally is focused around the use and development of computational modeling tools to evaluate how changes to a protein sequence, and therefore structure, results in a modulation of function. As members of the Rosetta Commons the majority of the modeling work carried out in the lab is done within the Rosetta Molecular Modeling Suite. We follow up the in silico modeling through in vitro studies leveraging recent breakthroughs from the field of synthetic biology to experimentally evaluate the properties of the designed proteins. On occasion we conduct in vivo studies of how the engineered proteins work within living organisms, however these studies are often done in collaboration with other groups. To date we have discovered and engineered enzymes to treat celiac disease, fight anthrax infections, catalyze novel chemistry never before observed in nature, produce high value chemicals, fixate carbon dioxide, and modulate the properties of various foods we eat.
Graduate Group Affiliations
O'Brien, T.E., S.J. Bertolani, D.J. Tantillo, and J.B. Siegel, Mechanistically informed predictions of binding modes for carbocation intermediates of a sesquiterpene synthase reaction. Chemical Science, 2016. 7(7): p. 4009-4015.
Carlin, D.A.*, R.W. Caster*, X. Wang, S.A. Betzenderfer, C.X. Chen, V.M. Duong, C.V. Ryklansky, A. Alpekin, N. Beaumont, H. Kapoor, N. Kim, H. Mohabbot, B. Pang, R. Teel, L. Whithaus, I. Tagkopoulos, and J.B. Siegel, Kinetic Characterization of 100 Glycoside Hydrolase Mutants Enables the Discovery of Structural Features Correlated with Kinetic Constants. PLoS One, 2016. 11(1): p. e0147596.
Siegel, J.B.*, A.L. Smith*, S. Poust, A.J. Wargacki, A. Bar-Even, C. Louw, B.W. Shen, C.B. Eiben, H.M. Tran, E. Noor, J.L. Gallaher, J. Bale, Y. Yoshikuni, M.H. Gelb, J.D. Keasling, B.L. Stoddard, M.E. Lidstrom, and D. Baker, Computational protein design enables a novel one-carbon assimilation pathway. Proc Natl Acad Sci U S A, 2015. 112(12): p. 3704-9.
Mak, W.S., S. Tran, R. Marcheschi, S. Bertolani, J. Thompson, D. Baker, J.C. Liao, and J.B. Siegel, Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway. Nat Commun, 2015. 6: p. 10005.
Lucas, J.E. and J.B. Siegel, Quantitative functional characterization of conserved molecular interactions in the active site of mannitol 2-dehydrogenase. Protein Sci, 2015. 24(6): p. 936-45.
Harger, M.*, L. Zheng*, A. Moon, C. Ager, J.H. An, C. Choe, Y.L. Lai, B. Mo, D. Zong, M.D. Smith, R.G. Egbert, J.H. Mills, D. Baker, I.S. Pultz, and J.B. Siegel, Expanding the product profile of a microbial alkane biosynthetic pathway. ACS Synth Biol, 2013. 2(1): p. 59-62.
Gordon, S.R.*, E.J. Stanley*, S. Wolf, A. Toland, S.J. Wu, D. Hadidi, J.H. Mills, D. Baker, I.S. Pultz, and J.B. Siegel, Computational design of an alpha-gliadin peptidase. J Am Chem Soc, 2012. 134(50): p. 20513-20.
Eiben, C.B.*, J.B. Siegel*, J.B. Bale, S. Cooper, F. Khatib, B.W. Shen, F. Players, B.L. Stoddard, Z. Popovic, and D. Baker, Increased Diels-Alderase activity through backbone remodeling guided by Foldit players. Nat Biotechnol, 2012. 30(2): p. 190-2.
Wu, S.J., C.B. Eiben, J.H. Carra, I. Huang, D. Zong, P. Liu, C.T. Wu, J. Nivala, J. Dunbar, T. Huber, J. Senft, R. Schokman, M.D. Smith, J.H. Mills, A.M. Friedlander, D. Baker, and J.B. Siegel, Improvement of a Potential Anthrax Therapeutic by Computational Protein Design. Journal of Biological Chemistry, 2011. 286(37): p. 32586-32592.
Siegel, J.B.*, A. Zanghellini*, H.M. Lovick, G. Kiss, A.R. Lambert, J.L. St Clair, J.L. Gallaher, D. Hilvert, M.H. Gelb, B.L. Stoddard, K.N. Houk, F.E. Michael, and D. Baker, Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction. Science, 2010. 329(5989): p. 309-13.
- 2015 Acting Director Innovation Institute for Food and Health, UC Davis
- 2014 Business Development Chair, Rosetta Commons
- 2014 International Genetic Engineering Machines Competition: Grand Prize
- 2014 Alfred P. Sloan Research Fellow
- 2013 National Academies Education Fellow
- 2012 Founder: PvP Biologics, Seattle, WA, United States
- 2012 Undergraduate Research Mentorship Award, University of Washington
- 2011 International Genetic Engineering Machines Competition: Grand Prize
- 2011 Fred Hutchinson Cancer Research Center Harold M. Weintraub Graduate Student Award
- 2010 International Genetic Engineering Machines Competition: Best Health and Medicine
- 2007 Founding Member: Bio Architecture Labs, Berkeley, CA, United States
- 2006 Molecular Biophysics NIH Fellow
- 2004 Summer Undergraduate Research Fellowship at the UC, Davis
- 2004 Presidents Undergraduate Fellowship at the UC, Davis