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Brian Sykes

 

Sykes70.jpg
Distinguished University Professor
Ph.D., Stanford University
Department of Biochemistry
Faculty of Medicine & Dentistry
University of Alberta
419a Medical Sciences Building
Edmonton, Alberta, Canada  T6G 2H7 

 

Tel: 780.492.5460
Lab Tel: 780.492.3006
Fax:  780.492.0886
 
Research:
 
Our research involves the elucidation of the structure, dynamics and function of proteins; including the role of intrinsically unfolded regions in regulating biological interactions. The major systems focus of our research is cardiovascular disease. In particular, we are interested in the function of the proteins that make up the thin filament of skeletal and cardiac muscle and regulate contraction; focusing on the calcium sensitive interactions between actin, tropomyosin, and troponin. We are presently studying the effects of drug binding, phosphorylation, acidosis and FHC mutations in the cardiac system. Our major tool is nuclear magnetic resonance spectroscopy, especially the use of multi-nuclear and multi-dimensional NMR techniques combined with the computational techniques of energy minimization and molecular dynamics to determine the structure of proteins in solution. We are also studying prion proteins in order to understand the mechanism of the conversion from the cellular to the Scrapie form; using NMR based metabolomic studies to diagnose human disease; and developing NMR methods for the study of the structure of membrane proteins.
 
Lab Members:
 
Fangze Cai, Graduate Student
Zelin Fu, Graduate Student
Brittney Klein, Lab Assistant

Selected Publications:
 
Wang, D., Robertson, I.M., Li, M.X., McCully, M., Crane, M.L., Luo, Z., Tu, A., Daggett, V., Sykes, B.D., and  Regnier, M. Structural and functional consequences of the cardiac troponin C L48Q Ca2+-sensitizing mutation.
 
Pineda-Sanabria, S., Robertson, I.M., Li, M.X. and Sykes, B.D. Interaction between the regulatory domain of cardiac troponin C and the acidosis resistant cardiac troponin I A162 Cardiovascular Research 97(3); 481-489 (2013).
 
Lee, B.L., Sykes, B.D. and Fliegel, L.  Structural and Functional Insights into the Cardiac Na+/H+ Exchanger, Journal of Molecular and Cellular Cardiology, 61(08): 60-76 (2013).
Robertson IM, Pineda-Sanabria SE, Holmes PC, Sykes BD, Conformation of the critical pH sensitive region of troponin depends upon a single residue in troponin I, Archives of Biochemistry and Biophysics, 552-553:40-49 (2014).
 
Hwang PM,  Cai F, Pineda-Sanabria SE, Corson DC, and Sykes BD, The intrinsically disordered cardiac-specific N-terminal region of troponin I positions the  regulatory domain of troponin C, Proc Natl Acad USA, 111(40), 14412-14417 (2014).
 
Lindert S, Li MX, Sykes BD, and McCammon JA, Computer-aided drug discovery  approach finds calcium sensitizer of the cardiac troponin complex, Chemical Biology & Drug Design, 85(2), 99-106 (2015).
 
Hwang PH and Sykes BD Targeting the sarcomere to correct muscle function, Nat Rev Drug Discovery 14, 313-328 (2015).