Research projects

Single-molecule fluorescence imaging and structural studies of proteins and protein complexes that regulate gene expression
How do the molecular structures and dynamics of these proteins and protein complexes together enable their function? Research efforts in the Deindl Lab are aimed at addressing this question using a combination of single-molecule fluorescence imaging approaches, structural techniques (cryo-EM, SAXS, X-ray crystallography), biochemistry and computer simulations.

In order to investigate this dynamic nature, we explore single-molecule fluorescence imaging approaches to directly visualize essential cellular processes in real time. The underlying interactions between biomolecules or conformational changes often involve distance changes at a nanometer length scale (1–10 nm). Fluorescence resonance energy transfer (FRET) is a spectroscopic technique that enables the observation of distance changes at this length scale with high sensitivity and in real time. Complex dynamics can be difficult to capture in classical bulk experiments since ensemble averaging can obscure the presence of multiple kinetic pathways or transient states. However, investigations at the single-molecule level, however, can allow us to directly observe these processes and to correlate structural dynamics with function. We hope to combine real-time dynamic information from these single-molecule experiments with biochemical and structural data in order to create ‘molecular movies’ of proteins and protein complexes at work that provide a quantitative and mechanistic understanding of their function.

We study the structural architecture of molecular machines using various techniques including cryo-electron microscopy, X-ray crystallography, ,small angle X-ray scattering (SAXS), and cross-linking mass spectrometry. Ultimately, we hope to combine structural data and biochemistry with real-time dynamic information from single-molecule experiments in order to provide a more complete quantitative and mechanistic understanding of protein function.