Applied Physics Seminar
Super-resolution fluorescence imaging and applications to aggregation-prone proteins in cells
The diffraction resolution barrier in far-field optical imaging has been radically overcome for the widely used fluorescence contrast mode by exploiting transitions between signal-giving (i.e. fluorescent) and dark molecular states. Switching between the two allows the discrimination of adjacent features separated by much less than the optical wavelength. Time-sequential imaging and nanometer-level localization of stochastically isolated fluorescing single molecules is at the heart of a class of methods termed single-molecule active control microscopy, while other schemes induce the switching between the dark- and signal-giving state within optically targeted sample regions of sub-diffraction extent. In this talk, I will first introduce the main principles underlying super-resolution microscopy. Using Huntington's Disease as a model case, I will then describe what kind of information can be obtained by high-resolution optical methods about the intracellular fate of aggregation-prone proteins, focusing on polyQ-expanded mutant huntingtin in neuronal model cells and in neurons. I will summarize progress in extending these methods to the third spatial dimension and will highlight some further methodological aspects of great current interest in the field.
More about the speaker: Steffen J. Sahl is presently a postdoctoral fellow at Stanford University, having earned his doctorate in physics (Heidelberg University, Germany) for thesis work at the Max Planck Institute for Biophysical Chemistry, Göttingen, Germany, in 2010. Steffen also holds degrees in physics from Cambridge University, England. His current research interests are in single-molecule optical analysis and imaging, in particular the further development of three-dimensional super-resolution fluorescence microscopies, and applying these methods to better understand the aggregation behavior of amyloid proteins in neurodegenerative disease.
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