Claudiu GradinaruPh.D. | Professor | Physics | Biophysics and Physical Chemistry
single-molecule biophysics, intrinsically-disordered proteins, GPCRs, computational methods, bioanalytical chemistry
Gradinaru biophysics research laboratory uses advanced laser and detection technology to capture conformational dynamics and molecular interactions at the single-molecule level. Single-molecule techniques are widely applied in life sciences and nanotechnology due to their unique ability to go beyond the intrinsic disorder and complexity of biological systems and provide new insights for how they work and for therapeutic intervention. Ultrasensitive microscopes in our lab, designed and built specifically for single-molecule fluorescence imaging and spectroscopy, provide a wide range of photon-level experimental capabilities, making the lab unique in Canada. Currently, the Gradinaru lab focuses on two main directions of research. First, we integrate single-molecule fluorescence data with other structural data (NMR, SAXS) and polymer physics theory to understand the determinants of “fuzzy structures” in biology and how intrinsically-disordered proteins (IDPs) interact with other molecules. Second, we measure nanometer-scale distances and nanosecond-to-second dynamics in G protein coupled-receptors (GPCRs), a large class of membrane proteins that are the main target of medicinal drugs. Our goal is to define how/when/where GPCRs activate and oligomerize in the cell membrane and how their innate structural flexibility couples to quaternary organization and biased signaling.
PHY100H5, PHY332H5, and PHY347H5 (undergraduate); PHY2707H1 (graduate)
Gomes, G.-N. W.; Krzeminski, M.; Namini, A.; Martin, E. W.; Mittag, T.; Head-Gordon, T.; Forman-Kay, J. D.; Gradinaru, C. C., Conformational Ensembles of an Intrinsically Disordered Protein Consistent with NMR, SAXS, and Single-Molecule FRET. Journal of the American Chemical Society 2020, 142 (37), 15697-15710.
Dawson, J. E.; Bah, A.; Zhang, Z.; Vernon, R. M.; Lin, H.; Chong, P. A.; Vanama, M.; Sonenberg, N.; Gradinaru, C. C.; Forman-Kay, J. D., Non-cooperative 4E-BP2 folding with exchange between eIF4E-binding and binding-incompatible states tunes cap-dependent translation inhibition. Nature Communications 2020, 11 (1), 3146.
Lincoff, J.; Haghighatlari, M.; Krzeminski, M.; Teixeira, J. M. C.; Gomes, G.-N. W.; Gradinaru, C. C.; Forman-Kay, J. D.; Head-Gordon, T., Extended experimental inferential structure determination method in determining the structural ensembles of disordered protein states. Communications Chemistry 2020, 3 (1), 74.
Garry, J., Li, Y. Shew, B., Gradinaru, C.C., and Rutenberg, A. R., (2020). Bayesian Counting of Photobleaching Steps with Physical Priors. J. Chem. Phys. 152(2): 024110.
Ahmed, S.M., Nishida-Fukuda, H., Li, Y., McDonald, W.H., Gradinaru, C.C., and Macara, I.G. (2018). Exocyst Dynamics during Vesicle Tethering and Fusion. Nature Communications, volume 9, 5140.
Li, Y., Shivnaraine, R.V., Huang, F., Wells, J.W., and Gradinaru, C.C. (2018). Ligand-Induced Coupling between Oligomers of the M2 Receptor and the Gi1 Protein in Live Cells. Biophys. J., 115, 881-895.
Fernandes, D.D., Bamrah, J., Kailasam, S., Li, Y., Gomes, G.-N., Wieden, H.-J., and Gradinaru, C.C. (2017). Characterization of Fluorescein Arsenical Hairpin (FlAsH) as a Probe for Single-Molecule Fluorescence Spectroscopy. Scientific Reports, 7:13063, DOI:10.1038/s41598-017-13427-8.
Song, J., Gomes, G.-N., Shi, T., Gradinaru, C.C., and Chan, H.S. (2017). Conformational Heterogeneity and FRET Data Interpretation for Dimensions of Unfolded Proteins. Biophys. J., 113, 1012-1024.
Gomes, G.-N. and Gradinaru, C.C. (2017). Insights into the Conformations and Dynamics of Intrinsically Disordered Proteins using Single-Molecule Fluorescence. BBA - Proteins and Proteomics, Special Issue “Biophysics in Canada”, 1865, 1696-1706.
Zhang, Z., Yomo, D. and Gradinaru, C. C. (2017). Choosing the Right Fluorophore for Single-Molecule Fluorescence Studies in a Lipid Environment. BBA Biomembranes, 1859, 1242–1253.
Shivnaraine, R.V., Fernandes, D. D., Ji, H., Li, Y., Zhang, Z., Kelly, B., Han, N., Huang, F., Sankar, K. S., Dubbins, D. N., Rocheleau, J. V., Wells, J. W. and Gradinaru, C. C. (2016). Single-Molecule Analysis of the Supramolecular Organization of the M2 Muscarinic Receptor and the Gαi1 Protein. J. Am. Chem. Soc. 138 (36), 11583–11598.
Fernandes, D. A., Fernandes, D. D., Li, Y., Wang, Y., Zhang, Z., Rousseau, D., Gradinaru,* C. C. and Kolios,* M. C. (2016). Synthesis of Stable Multifunctional Perfluorocarbon Nanoemulsions for Cancer Therapy and Imaging. Langmuir, 32, 10870-10880.
Shivnaraine,* R.V., Kelly, B., Sankar, K. S., Redka, D.S., Han, Y. R., Huang, F., Elmslie, G., Pinto, D., Li, Y., Rocheleau, J. V., Gradinaru,* C. C., Ellis,* J. and Wells,* J. W. (2016). Allosteric Modulation in Monomers and Oligomers of a G Protein-Coupled Receptor, eLife, 10.7554/eLife.11685.
Mazouchi, A., Zhang, Z., Bahram, A., Gomes, G.-N., Lin, H., Song, J., Chan, H. S., Forman-Kay, J. D. and Gradinaru, C.C. (2016). Conformations of a Metastable SH3 Domain Characterized by smFRET and an Excluded-Volume Polymer Model. Biophys. J., 110, 1510–1522.