David Libich, Ph.D.
All cellular functions, activities, and communications are mediated by protein interactions. Despite their crucial importance, we know relatively little about many of these interactions due in large part to experimental limitations of structural biology. The central theme of the Libich Lab revolves around the determination of the structure and elucidation of the molecular mechanisms of highly dynamic and transient protein interactions. In conjunction with conventional biophysical approaches, we employ a host of cutting-edge NMR methods designed to detect and quantify kinetic, dynamic and structural information from such systems. Our current efforts are focused on understanding the assembly and functional interactions of low-complexity RNA-binding proteins involved in cancer and neurodegenerative processes. These types of proteins are challenging targets for biophysical characterization due to their extreme structural heterogeneity and propensity to aggregate. In particular, we are interested in the oncogenic fusion protein EWS-Fli1 and the structural implications of its role as the sole driver of Ewing's sarcoma. By characterizing, at atomic resolution, the structural features that contribute to both EWS-Fli1 self-association and its macromolecular interactions we will seek to understand the molecular basis of how it influences the genetic program of the cell. In a wider context, these studies will teach us more about the fundamental mechanisms of protein interactions, in both healthy and disease states.
pediatric cancer, Ewing's sarcoma, synovial sarcoma, neurodegenerative processes, ALS, mitochondrial dysfunction, apoptosis, chaperones, protein folding, intrinsic disorder, intrinsically disordered proteins, cancer biology
nuclear magnetic resonance (NMR), fluorescence spectroscopy, circular dichroic spectroscopy, analytical ultracentrifugation, light scattering, protein purification, site-directed mutagenesis, molecular cloning, biophysical and biochemical approaches
Confinement and Stabilization of Fyn SH3 Folding Intermediate Mimetics within the Cavity of the Chaperonin GroEL Demonstrated by Relaxation-Based NMR. Libich DS, Tugarinov V, Ghirlando R, Clore GM Biochemistry: 2017-02-21; 56(7); 903-906 Epub: 2017-02-08. PMID: 28156097 LINK:
Reply to Marchenko et al.: Flux analysis of GroEL-assisted protein folding/unfolding.Libich DS, Tugarinov V, Clore GM Proc Natl Acad Sci U S A: 2015-12-15; 112(50); E6833-4 Epub: 2015-11-24. PMID: 26604310 LINK:
The energetics of a three-state protein folding system probed by high-pressure relaxation dispersion NMR spectroscopy. Tugarinov V, Libich DS, Meyer V, Roche J, Clore GM Angew Chem Int Ed Engl: 2015-09-14; 54(38); 11157-61 PMID: 26352026 LINK:
Intrinsic unfoldase/foldase activity of the chaperonin GroEL directly demonstrated using multinuclear relaxation-based NMR. Libich DS, Tugarinov V, Clore GM Proc Natl Acad Sci U S A: 2015-07-21; 112(29); 8817-23 Epub: 2015-06-29. PMID: 26124125 LINK:
Characterizing methyl-bearing side chain contacts and dynamics mediating amyloid β protofibril interactions using ¹³C(methyl)-DEST and lifetime line broadening. Fawzi NL, Libich DS, Ying J, Tugarinov V, Clore GM
Angew Chem Int Ed Engl: 2014-09-22; 53(39); 10345-9 Epub: 2014-08-11. PMID: 25130489 LINK: The intrinsically disordered structural platform of the plant defence hub protein RPM1-interacting protein 4 provides insights into its mode of action in the host-pathogen interface and evolution of the nitrate-induced domain protein family.
Sun X, Greenwood DR, Templeton MD, Libich DS, McGhie TK, Xue B, Yoon M, Cui W, Kirk CA, Jones WT, Uversky VN, Rikkerink EH FEBS J: 2014-09-01; 281(17); 3955-79 Epub: 2014-08-08. PMID: 25039985 LINK:
Probing the transient dark state of substrate binding to GroEL by relaxation-based solution NMR. Libich DS, Fawzi NL, Ying J, Clore GM Proc Natl Acad Sci U S A: 2013-07-09; 110(28); 11361-6 Epub: 2013-06-24. PMID: 23798407 LINK:
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University of Guelph Ph.D. (Biophysics)
University of Guelph B.Sc. (Biochemistry)