My scientific efforts are focused on combining computational and experimental tools to develop a fundamental knowledge of enzyme catalysis, and applying those principles to design novel proteins of therapeutic or commercial interest. Currently I am working with an international community on the development of Rosetta computational methodology for predicting and designing macromolecular structures, interactions, and functions. Using this methodology I have completed the de novo design of enzymes capable of catalyzing chemical reactions not found in nature, such as the Diels-Alder reaction. This was followed up by working with an online community, Foldit, to further engineer these proteins for enhanced activity. Most recently I have worked on the redesign of naturally occurring enzymes for the degradation of immunogenic gluten proteins, to develop a novel CO2 fixation pathways, and design of a novel anthrax therapeutic. My current focus is on the design of novel biofuel and commodity chemical biosynthetic pathways, the development of novel therapeutics, and the general understanding of the relationship between protein sequence, structure, and function.
For more information, visit the Siegel Lab Website.
Harger M, Zheng L, Moon A, Ager C, An JH, Choe C, Lai YL, Mo B, Zong D, Smith MD, Egbert RG, Mills JH, Baker D, Pultz IS, Siegel JB. Expanding the Product Profile of a Microbial Alkane Biosynthetic Pathway. ACS Synthetic Biology 2012. DOI: 10.1021/sb300061x
Eiben CB*, Siegel JB*, Bale J, Foldit Players, Khatib F, Cooper S, Shen BW, Stoddard BL, Popovic Z, Baker D. Increased Diels-Alderase activity through FoldIt player guided backbone remodeling. Nature Biotechnology 2012: 30: 190-192 DOI: 10.1038/nbt.2109
Wu SJ, Eiben CB, Carra JH, Huang I, Zong D, Liu P, Wu C, Nivala J, Dunbar J, Huber T, Senft J, Schokman R, Smith MD, Mills JH, Friedlander AM, Baker D, Siegel JB. Improvement of a potential anthrax therapeutic by computational protein design. JBC 2011: 286: 32586-32592. DOI: 10.1074/jbc.M111.251041
Siegel JB, Zanghellini A, Lovick HM, Kiss G, Lambert AR, St Clair JL, Gallaher JL, Hilvert D, Gelb MH, Stoddard BL, Houk KN, Michael FE, Baker D. Computational design of an enzyme catalyst for a stereoselective bimolecular Diels-Alder reaction. Science 2010: 329: 309-313. DOI: 10.1126/science.1190239
Honors and Awards
- 2012 Undergraduate Research Mentorship Award, University of Washington
- 2011 Instructor, International Genetic Engineering Machines Competition, Americas Region: Grand Prize, Gold Medal, & Best New Engineered Part
- 2011 Fred Hutchinson Cancer Research Center Harold M. Weintraub Graduate Student Award
- 2010 Instructor, International Genetic Engineering Machines Competition: Gold Medal, Best Health & Medicine Project
- 2009 Instructor, International Genetic Engineering Machines Competition: Gold Medal
- 2007 Molecular Biophysics NIH Fellow
- 2006 Molecular Biophysics NIH Fellow
- 2004 Summer Undergraduate Research Fellowship at the UC, Davis
- 2004 Presidents Undergraduate Fellowship at the UC, Davis