Byron Scott DeLaBarre, M.Sc., Ph.D. byron.delabarre@gmail.com 650 468 5677 (cell) / 781 646 2814 (home) I am a research scientist with strong skills in applying x-ray crystallography and other biophysical techniques to elucidating protein structure. I have successfully used these skills to understand protein conformational changes, protein:ligand interactions and to drive structure-based drug design. I am primarily a structural biologist, but my skills in molecular biology, protein chemistry, biochemistry, enzymology and organic chemistry enable effective interdisciplinary interactions and/or management of groups undertaking these activities. I have multiple years of experience with the drug design process in an industrial setting, most recently in the field of oncology. My postdoctoral work involved the study of large multi-protein membrane associated complexes and my graduate studies centered on solving the de novo structure of an antibiotic drug target. I am seeking a position that will allow me to apply these skills and grow into a management role supervising a group focused on making biomedical advances. Skills Molecular biology DNA construct design PCR cloning protein expression fermentor growth protein purification protein chemistry protein crystallization Biophysics / Biochemistry X-ray diffraction enzyme kinetics CD SEC-MALLS fluorimetry UV/visible spectroscopy mass spectroscopy ITC/DSC Computational Unix/Linux administration python and shell scripting bioinformatics x-ray crystallography data processing protein structure refinement protein structure analysis homology modeling Experience Harvard Medical School, Dept of Cell Biology Scientist Structural studies of membrane channels involved in protein translocation Structural studies of activated and inhibited protein chaperones 2008- Millennium Pharmaceuticals, Structural Biology Group in Department of Chemistry 2006-2008 Scientist I Provided structural information to oncology chemistry for multiple protein targets complexed with small molecule inhibitors from medicinal chemistry group Performed primary literature research on new protein targets, designed expression constructs, purified and crystallized protein, solved structures with novel small molecule compounds and communicated results to project groups Consulted with biochemistry and cellular biology groups on protein homeostasis research in academia through active participation in working and literature review groups Hosted external speakers from academic research institutions as part of novel therapeutic target identification efforts Resume of Byron DeLaBarre / byron.delabarre@gmail.com / 650 468 5677 page 2/4 Experience (continued) Stanford University/HHMI, Depts. Mol. & Cell Phys., Neurobiology & Neuroscience 2001-2006 Yale University/HHMI, Dept. Molecular Biology & Biophysics 2000-2001 Postdoctoral Research Associate with Dr. Axel T. Brunger Cloned, expressed and purified full length mammalian p97/VCP, a 540 kDa membrane associated ATPase that interacts with misfolded proteins in the secretory pathway Determined first complete structure of p97/VCP by X-ray crystallography and three-dimensional reconstruction from cryo-electron microscopy images in multiple nucleotide states. Implemented steady state kinetics assay for ATP hydrolysis by p97/VCP and then successfully used the enzymatic conditions to identify protein substrates of p97/VCP Designed and oversaw implementation of a cell based assay for examining protein misfolding to study p97/VCP mutants based upon the structural findings. Created new methods and refined existing approaches for working with low resolution X-ray diffraction data and the molecular dynamics of models resulting from these studies. Published work in upper tier journals and presented at scientific meetings Bio-Mega Pharmaceuticals, Synthetic Chemistry Department Student Researcher Examined new methods of chiral selectivity in organic synthetic chemistry Synthesized a small fragment of a complex natural product, ionomycin 1990-1991 Notre Dame Radiation Research Lab (DOE) Student Researcher Employed picosecond laser spectroscopy to characterize novel dye molecules 1990 Education Ph.D. Biochemistry McMaster University 1996-2000 Advisor: Dr. A. M. Berghuis Thesis title: The Structure of Homoserine Dehydrogenase from S. cerevisae M.Sc. Inorganic Chemistry McMaster University 1993-1996 Advisor: Dr. C. J. L. Lock (deceased) Thesis title: Chemical Modeling of Zinc Enzymes B.Sc. Honors Applied Chemistry University of Waterloo 1988-1993 Advisor: Dr. L. F. Nazar Senior thesis topic: Characterization of Battery Materials by Powder X-ray Diffraction Honors 2000: Howard Hughes Medical Institute Postdoctoral Fellowship (Research Associate) 2000: Best Senior Graduate Student Seminar – McMaster Dept. of Biochemistry 1999: Ludo Frevel Award – International Centre for Diffraction Data Graduate Scholarship 1998: Pauling Award, 1998 American Crystallographic Association Annual Meeting 1994: Tuition Scholarship for American Crystallographic Association Summer School 1993: Centennial Scholarship, McMaster University 1990: National Science and Engineering Research Council Industrial Research Award 1988-93: Dean’s List, University of Waterloo 1988: Finished in top 1.5 Percentile for Canadian High School Chemistry Contest (Chem13 News). Resume of Byron DeLaBarre / byron.delabarre@gmail.com / 650 468 5677 page 3/4 Peer Reviewed Publications Anderson M.J., DeLaBarre B., Raghunathan A., Palsson B.O., Brunger A.T., Quake S.R. (2007). Crystal structure of a hyperactive Escherichia coli glycerol kinase mutant Gly230 --> Asp obtained using microfluidic crystallization devices. Biochemistry. 46(19), 5722-31. DeLaBarre, B., Brunger, A.T. (2006). Considerations for the refinement of low-resolution crystal structures. Acta(D) Biol. Cryst. 62(8), 923-32. DeLaBarre, B., Christianson, J.C., Kopito, R.R., Brunger, A.T. (2006). Central Pore Residues Mediate the p97/VCP Activity Required for ERAD. Mol. Cell 22(44), 451-62. DeLaBarre, B., Brunger, A.T. (2005). Nucleotide dependent motion and mechanism of action of p97/VCP. J. Mol. Bio. 347(2), 437-452. Brill, L.M., Dechongkit, S., DeLaBarre, B., Stroebel, J., Beachy, R.N., Yeager, M., (2004) Dimerization of Recombinant TMV Movement Protein. J. Virol 78(7), 3372-7. DeLaBarre, B., Brunger, A.T. (2003). Complete Structure of p97/VCP Reveals Communication between Nucleotide Domains. Nature Structural Biology, 10(10), 856-63. Rouiller, I., DeLaBarre, B., May, A.P., Weiss, W., Brunger, A.T., Milligan, R., Wilson-Kubalek, E (2002) Conformational Changes of the Multifunction p97 AAA ATPase during its ATPase Cycle. Nature Structural Biology, 9(12), 950-7. DeLaBarre, B., Thompson, P.R., Wright, G.D., Berghuis, A.M. (2000) The Structure of Homoserine Dehydrogenase Suggests a Novel Mechanism for Oxidoreductases. Nature Structural Biology, 7(3), 238-44. DeLaBarre, B., Jacques, S.L., Pratt, C.E., Ruth, D. Wight, G.D., Berghuis, A.M. (1998) Crystallization and Preliminary X-ray Diffraction Studies of Homoserine Dehydrogenase from S. cerevisae. Acta Cryst. D., 54, 413-415. Das, S., Kamat, P.V., DeLaBarre, B., Thomas, K.G., Ajayaghosh, A., George, M.V. (1992) Photophysics and Photochemistry of Squaraine Dyes. J. Phys. Chem., 96, 10327-30. Other Publications and Presentations DeLaBarre, B., Christianson, J.C., Kopito, R.R., Brunger, A.T. (2007). Central Pore Residues Mediate the p97/VCP Activity Required for ERAD. 7th International Meeting on AAA Proteins. (Cirencester, UK). [Invited Talk] DeLaBarre, B., Brunger, A.T. (2005). The AAA Protein VCP/p97. 6th International Meeting on AAA Proteins. (Styria, Austria). [Invited Talk] DeLaBarre, B., Christianson, J. C., Kopito, R.R., Brunger, A.T. (2005). ATP Dependant Motions in VCP/p97 and its Relation to the 19S Regulatory Component of the Proteosome. Keystone Symposium on Ubiquitin and Signaling. (Taos, NM). [Poster] DeLaBarre, B., Brunger, A.T. (2004). Structure and Function of VCP/p97. FASEB Conference on Ubiquitination & Cellular Regulation. (Saxtons River, VT). [Poster] Resume of Byron DeLaBarre / byron.delabarre@gmail.com / 650 468 5677 page 4/4 Other Publications and Presentations (continued) DeLaBarre, B., Brunger, A.T. (2004). The Structure of Full Length VCP/p97: A Success Story with Low Resolution Crystal Data. 29th Lorne Conference on Protein Structure & Function. (Lorne, Australia) [Talk] DeLaBarre, B., Brunger, A.T. (2003). The X-Ray Structure of Full Length VCP/p97. Conformational Diseases of the Secretory Pathway Keystone Symposium. (Taos, NM). [Invited Talk] DeLaBarre, B., Brunger, A.T. (2003). The Crystal Structure of VCP: How Much Information is There in a Structure of Moderate Resolution? 16th West Coast Protein Crystallography Workshop. (Monterey, CA). [Talk] Brunger, A.T., DeLaBarre, B. (2003). NSF and p97/VCP: Similar at First, Different at Last. FEBS Letters, 555(1), 126-33. [Invited review for 2003 Nobel Committee Membrane Protein Meeting] DeLaBarre, B., Brunger, A.T. (2003). The Crystal Structure of Full Length VCP/p97: Two AAA Domains are Better than One. 5th International Meeting on AAA Proteins. (Warrenton, VA) [Invited Talk] Rouiller I, DeLaBarre B, May AP, Weiss WI, Brunger AT, Milligan RA, Wilson-Kubalek EM (2002). Conformational changes of the multifunction VCP/p97 AAA ATPase during the ATPase cycle. Mol. Bio. Cell 13: 263A-263A,1480 ASCB Meeting [Poster] DeLaBarre, B., Thompson, P.R., Wright, G.D., Berghuis, A.M. (1999). The Structure of Homoserine Dehydrogenase from S. cerevisae Reveals a Novel Catalytic Fold. Protein Science, vol. 8, Suppl. 1 (Boston, MA) [Poster]. DeLaBarre, B., Berghuis, A.M. (1999). The Structure of Homoserine Dehydrogenase: A Story of Economical Phasing. Abstracts of the American Crystallographic Society, 26 ed. (Buffalo, NY) [Poster] DeLaBarre, B., Berghuis, A.M. (1998). Facing the Phasing Problems of Homoserine Dehydrogenase. Abstracts of the American Crystallographic Society, 25 ed. (Washington, DC) [Poster – winner best graduate student poster]. DeLaBarre, B., Wright, G.D. Berghuis, A.M. (1996). Crystallographic Studies of Homoserine Dehydrogenase for the Design of Novel Antifungal Agents. Abstracts of the 17th IUCR Congress (Seattle, WA) [Poster]. DeLaBarre, B., Lock, C. J. L. (1995). A Small Molecule Model of a Zinc Enyzme Active Site. Abstracts of the 78th Canadian Society for Chemistry Conference and Exhibition. (Guelph, Canada) [Poster].