The Gradinaru biophysics research laboratory employs advanced laser and detection technology to measure the structural heterogeneity of biological molecules and to capture the dynamics of molecular conformations and interactions at the single-molecule level. Single-molecule fluorescence (SMF) techniques are now widely used in life sciences, including applications focused on studying protein and RNA folding, molecular motors, enzymatic activity, DNA replication, and the dynamics of ion channels and membrane receptors. Single-molecule experimental approaches have the unique capability to observe and quantify the disorder and complexity of biological systems and can provide crucial feedback for theory and for molecular dynamics simulations.

Over the years, we have built several ultrasensitive microscopes which can track fluorescent molecules with nanometer accuracy and on time scales from picoseconds to hours. Our instruments can simultaneously record multiple fluorescence parameters, such as wavelength, lifetime, anisotropy, anisotropy decay, photon bunching, etc, which can be used to infer a wealth of information about the states and the dynamics of biological molecules and their local environment. A remarkable range of single-molecule fluorescence modalities are available in the lab: smFRET, multi-parameter photon burst analysis, dual-color FCS, nanosecond-FCS, single-particle tracking, single-molecule photobleaching, FRAP, FLIM, one- and two-photon confocal imaging, and multi-color total internal reflection fluorescence microscopy.

Our main research projects focus on studying rapidly fluctuating conformations in intrinsically disordered proteins and drug-induced conformational and oligomerization dynamics of G-protein coupled receptors in the cell membrane. On top of that, we collaborate on projects aimed at characterizing the inhibitory action of new synthetic drugs against oncogenic proteins, and the physical properties of nanoparticles for drug delivery, biosensing and cancer imaging applications. By nature, our research is highly interdisciplinary and the lab members are being trained not only in Physics, but also in (bio)Chemistry, Statistical analysis, Computer programming, and Molecular and Cellular Biology. We have active collaborations with various groups in the Chemistry, Biochemistry and Pharmacy departments at UofT, at the Sick Kids Hospital in Toronto, as welll as external collaborators at Dalhousie and Vanderbilt and local industry partners.