Biophysics Research

The biophysics group comprises five faculty members interested in a wide array of topics ranging from structure and dynamics of biological macromolecules to collective behavior of macromolecular and cellular systems. The faculty members are joined in their endeavors by several postdoctoral research associates, and graduate and undergraduate students. More details can be obtained from web pages of individual groups or faculty members and from other areas of the Physics Department website.

Faculty: Marija Gajdardziska-Josifovska, A. Ourmazd, V. Raicu, D.K. Saldin, M. Schmidt and V. Yakovlev.

Abbas Ourmazd's research is aimed at developing innovative approaches for determining the structure and conformations of biological systems ranging from single molecules to whole cells at high resolution. The central hypothesis rests on new evidence that advanced algorithms stemming from Riemannian geometry, graph theory, and machine learning can be combined to forge a powerful new approach to biological structure determination in a way which circumvents the limits set by noise and radiation damage. These algorithms can be used with existing techniques, such as cryo-electron microscopy (cryo-EM), and emerging approaches exploiting the extreme brightness of X-ray Free Electron Lasers (XFELs). More generally, our work has important implications for tomography of faintly scattering, non-stationary objects at any length scale.

For more information: Ourmazd's research website

Valerică Raicu is interested in experimental and theoretical aspects of the structure and dynamics of macromolecular and cellular systems in vivo. One of the main research themes in his lab is imaging of protein activity and interactions in living cells. This study involves novel approaches to laser-scanning fluorescence microscopy with spectral and temporal resolution, which is used in conjunction with a process of non-radiative energy transfer between fluorescent molecules, called Förster (or fluorescence) resonance energy transfer (FRET). The second major research theme in Prof. Raicu's lab is the use of dielectric (or impedance) spectroscopy to probe the response to radiofrequency electrical fields of a material's electrical polarization in order to determine its physical and structural characteristics at the microscopic level. This method is particularly suitable for characterization of biological cells individually dispersed in suspension or as part of supracellular associations, such as tissues and organs.

For more information: Raicu's research website

Dilano Saldin's biophysics research is aimed developing methods for determining the structures of biological molecules from ensembles close to their natural environments, thus obviating the sometimes problematic need for crystallization. Examples are molecules in liquid solution, or proteins embedded in membranes. In the former case the molecules may be assumed to be oriented completely randomly, while in the latter, they are assumed to be randomly oriented about an axis normal to the membrane. Another configuration of partial orientational ordering from which we are extracting structural information is that of single molecules aligned by a laser, as well as molecules with completely arbitrary orientation, as in proposed experiments at a future x-ray free electron laser (XFEL). The theoretical approaches focus on analyzing angular correlations amongst scattered intensities in a spherical or circular harmonic basis, and generalization of fiber diffraction theory (which led to the elucidation of the DNA structure) most appropriately analyzed in a cylindrical harmonic basis.

For more information: Saldin's research website

Marius Schmidt’s research focuses on a unique method that unifies atomic structure with chemical kinetics: ultra-rapid, time-resolved X-ray structure analysis of proteins. This technique requires the brightest X-ray sources of the world, one of which is the close-by Advanced Photon Source at Argonne National Lab near Chicago. X-ray data collected there are four dimensional, with space and time as variables. With these data, chemical reactions can be observed directly in the protein crystals with a time-resolution of 100 pico-seconds and on the atomic length scale. The aim is to completely understand the catalyzed reaction including the atomic structures of the reaction intermediates and the corresponding kinetic mechanism. To analyze the large body of time-resolved X-ray data sophisticated and user-friendly software is required that is also developed by Prof. Schmidt’s research group. In addition, proteins are produced, purified and crystallized for “de-novo” X-ray structure analyses.
For more information: Schmidt's research website

Vladislav Yakovlev's work is aimed at the fundamental understanding of protein dynamics and developing innovative approaches to visualize this dynamics both in vitro and in vivo. The central hypothesis is that advanced optical microspectroscopy can provide sufficient information about the conformational state of those molecules in solution and inside a living cell. To achieve this goal, we strive to improve the sensitivity and selectivity of spectroscopic techniques based on spontaneous and nonlinear Raman scattering and optical harmonics generation. By combining these methods with single-molecule imaging and manipulation tools, we expect to achieve an unprecedented spatial and time resolution of molecular dynamics. In particular, we are using microfluidic devices to attain a fast initiation of chemical reactions, which are then probed by UV resonance Raman spectroscopy. In another ongoing effort, nonlinear optical microspectroscopy is used to interrogate the fast protein and lipid dynamics in mitochondrial and cellular membranes. The applied aspect of our research involves the development of novel technologies to sense the presence of just a few or, even single molecules and to provide biologists with new tools and instruments for non-invasive methods of a high-throughput chemical and structural analysis.