Professor, Biochemistry and Biophysics, UNC-CH PHD - State University of New York, Stony Brook (click for Full Publication List)

HONORS & AWARDS

• W.M.Keck Foundation Distinguished Young Scholar in Medical Research, 2005-2010
• Searle Scholar, 2004-2007
• Beckman Young Investigator, 2004-2007
• AAAS Newcomb Cleveland Prize, 2004
• Foresight Institute Feynman Prize in Nanotechnology, 2004
• Alfred P. Sloan Fellow, 2004

RESEARCH

Summary: The focus of my laboratory is the development and application of methods for protein design. Proteins are the ultimate nanomachines and we aim to develop methods that can be used to create novel proteins that perform useful tasks. Central to most projects in the laboratory is the molecular modeling software Rosetta. My laboratory is part of a multi institutional team of developers that maintains and extends the capabilities of Rosetta. We have used Rosetta to stabilize proteins, enhance protein binding affinities, redesign protein signaling networks, design new protein structures, and design new protein-protein interactions. We are continually striving to improve the accuracy of Rosetta as well as apply it to new and important biological problems.

Currently, my laboratory is focused on three projects: the design of protein-protein interactions, the design of proteins that can be turned on and off with the light, and the improvement of computational methods for performing protein simulations. Designed protein binders can serve as affinity reagents for the creation of new biosensors and can act as competitive inhibitors with therapeutic value. Light activatable proteins allow scientists to control the activity of proteins in living cells with spatial and temporal resolution. In collaboration with Klaus Hahn’s lab at UNC, we have created a photoactivable variant of the small GTPase Rac1 that allows biologists to use narrow beams of light to move cells around in living animals. Lastly, improvements to the core routines of Rosetta allow for more accurate design and prediction simulations by the thousands of laboratories that have licensed the Rosetta software.

Core Techniques:

• Rosetta molecular modeling program
• Protein Stabilization
• Protein Interface Design
• Protein Binding Analysis

To learn more about our research, please see our group web page.

SELECT PUBLICATIONS

• Stranges PB, Machius M, Miley MJ, Tripathy A, Kuhlman B. Computational design of a symmetric homodimer using β-strand assembly. Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20562-7.
• Der BS, Machius M, Miley MJ, Mills JL, Szyperski T, Kuhlman B. Metal-mediated affinity and orientation specificity in a computationally designed protein homodimer. J Am Chem Soc. 2012 Jan 11;134(1):375-85.
• Jha RK, Wu YI, Zawistowski J, Macnevin C, Hahn KM, Kuhlman B. Redesign of the  PAK1 Autoinhibitory Domain for Enhanced Stability and Affinity in Biosensor Applications. J Mol Biol. 2011 Aug 24
• Sammond DW, Bosch DE, Butterfoss GL, Purbeck C, Machius M, Siderovski DP, Kuhlman B. Computational design of the sequence and structure of a protein-binding peptide. (2011) J Am Chem Soc. 133(12):4190-2.
• Guntas G, Purbeck, C., Kuhlman, B. (2010) Engineering a Protein-Protein Interface using a Computationally Designed Library, Proc Natl Acad Sci, 107, 19296-301.
• Kleiger G, Saha A, Lewis S, Kuhlman B, Deshaies RJ. (2009) Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates. Cell 139, 957.
• Wu, Y, Frey, D., Lungu, O. I., Jaehrig, A., Schlichting, I., Kuhlman, B. and Hahn, K.M. (2009) A genetically encoded photoactivatable Rac controls the motility of living cells. Nature, 461, 104-108.
• Hu, X., Wang, H., Ke, H., & Kuhlman, B. (2007) High-resolution design of a protein loop. Proc Natl Acad Sci, 104, 17668-17673.
• Kuhlman, B., Dantas, G., Ireton, G., Varani, G., Stoddard, B., & Baker, D. (2003) Design of a novel globular protein fold with atomic level accuracy.  Science 302, 1364-1368.

CONTACT INFO

120 Mason Farm Rd
Campus Box # 7260
3096 Genetic Medicine Bldg
Chapel Hill, NC 27599

Office: 919-843-0188
Lab: 919-966-6781

bkuhlman@email.unc.edu

Lab Location: 3100D-F Genetic Medicine

Kuhlman Lab Website