Engineered biological systems, ranging from molecules with new functions to entire organisms, have tremendous practical importance; they can also fundamentally change how we ask questions about the biological principles of function and fitness. Our research aims to invent approaches to engineer new molecules that operate as predicted in biological contexts, and to utilize prediction and engineering to address fundamental questions on the relationship of molecular characteristics, cellular function and organismal fitness. To address the many current challenges in the field – from developing more predictive computational design methods to determining the requirements for function in cells – we combine concepts from computer science, physics, chemistry, mathematics, engineering and biology.
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Selected Publications
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Glasgow AA, Huang YM, Mandell DJ, Thompson M, Ritterson R, Loshbaugh AL, Pellegrino J, Krivacic C, Pache RA, Barlow KA, Ollikainen N, Jeon D, Kelly MJS, Fraser JS, Kortemme T. (2019) Computational design of a modular protein sense-response system. Science. 22;366(6468):1024-1028.
Kundert K, Lucas JE, Watters KE, Fellmann C, Ng AH, Heineike BM, Fitzsimmons CM, Oakes BL, Qu J, Prasad N, Rosenberg OS, Savage DF, El-Samad H, Doudna JA, Kortemme T. (2019) Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs. Nat Commun. 9;10(1):2127.
Ollikainen N, de Jong RM, Kortemme T. (2015) Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity. PLoS Comput Biol. 11(9):e1004335.
Hoersch D, Roh SH, Chiu W, Kortemme T. (2013) Reprogramming an ATP-driven protein machine into a light-gated nanocage. Nat Nanotechnol. 8(12):928-32.
Eames M, Kortemme, T. (2012). Cost-benefit tradeoffs in engineered lac operons. Science 336(6083): 911-915.
Kapp GT, Liu S, Stein A, Wong DT, Reményi A, Yeh BJ, Fraser JS, Taunton J, Lim WA, Kortemme T. (2012). Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair. Proc Natl Acad Sci U S A. 109(14): 5277-82.
Mandell DJ, Kortemme T. (2009). Computer-aided design of functional protein interactions.
Nat Chem Biol 5(11):797-807. (review)
Mandell DJ, Coutsias EA, Kortemme T. (2009). Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling. Nat Methods 6:551–552.
Oberdorf R, Kortemme T. (2009). Complex topology rather than complex membership is a determinant of protein dosage sensitivity. Mol Syst Biol. 5:253.
Smith CA, Kortemme T. (2008). Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction. J Mol Biol. 380(4):742-56.
Kundert K, Lucas JE, Watters KE, Fellmann C, Ng AH, Heineike BM, Fitzsimmons CM, Oakes BL, Qu J, Prasad N, Rosenberg OS, Savage DF, El-Samad H, Doudna JA, Kortemme T. (2019) Controlling CRISPR-Cas9 with ligand-activated and ligand-deactivated sgRNAs. Nat Commun. 9;10(1):2127.
Ollikainen N, de Jong RM, Kortemme T. (2015) Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity. PLoS Comput Biol. 11(9):e1004335.
Hoersch D, Roh SH, Chiu W, Kortemme T. (2013) Reprogramming an ATP-driven protein machine into a light-gated nanocage. Nat Nanotechnol. 8(12):928-32.
Eames M, Kortemme, T. (2012). Cost-benefit tradeoffs in engineered lac operons. Science 336(6083): 911-915.
Kapp GT, Liu S, Stein A, Wong DT, Reményi A, Yeh BJ, Fraser JS, Taunton J, Lim WA, Kortemme T. (2012). Control of protein signaling using a computationally designed GTPase/GEF orthogonal pair. Proc Natl Acad Sci U S A. 109(14): 5277-82.
Mandell DJ, Kortemme T. (2009). Computer-aided design of functional protein interactions.
Nat Chem Biol 5(11):797-807. (review)
Mandell DJ, Coutsias EA, Kortemme T. (2009). Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling. Nat Methods 6:551–552.
Oberdorf R, Kortemme T. (2009). Complex topology rather than complex membership is a determinant of protein dosage sensitivity. Mol Syst Biol. 5:253.
Smith CA, Kortemme T. (2008). Backrub-like backbone simulation recapitulates natural protein conformational variability and improves mutant side-chain prediction. J Mol Biol. 380(4):742-56.
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Highlights from the Lab
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Samuel's QBI interview for the 2017 Dr. Herbert Landahl Mathematical Biophysics Student Excellence Award.
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Amanda's 90-second video, "A generalized strategy for engineering biological sense/response pairs," wins 3rd place in the 2014 Synberc Perfect Pitch Contest!
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Our biosensor project wins first prize in Gen9's inaugural G-Prize contest
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