OSC Colloquium: Douglas Shepherd, "Scalable, high-speed, 3D imaging of molecular biology in action"

Abstract(s): 

Continued advancements in biomedical optical microscopy and fluorescent labeling techniques have enabled multi-dimensional visualization of biology in action at the single-molecule level. For example, multiple large-scale efforts are currently underway to create nanoscale spatial maps of thousands of individual RNA and protein species in millions of cells across all human organs. Many of the experiments across these efforts rely on multiplexed fluorescence molecular imaging. In fluorescence imaging, the optical microscope acts as a measurement device to generate a digital representation of fluorescent reporters within a sample. The quality and confidence of biological knowledge extracted from the resulting digital images depend on the molecular labeling strategy, the microscope's design, and detector choices. Compromises are often necessary to achieve the required volume, imaging speed, number of molecules, samples, or other biologically driven experimental design criteria. Such compromises inevitably increase uncertainty when quantifying molecular identity and dynamics. I will discuss our recent efforts to reduce uncertainty in quantitative molecular imaging through improvements to the optical methods and computational tools used for high-speed, high-resolution, multiplexed, and volumetric fluorescence molecular imaging. Our efforts include a high numerical aperture oblique plane microscopy framework for 3D spatial transcriptomics in human tissue and a digital micromirror-based structured illumination microscopy framework for live-cell, sub-diffraction limited imaging. 

Speaker Bio(s): 

Douglas Shepherd is an assistant professor in the Center for Biological Physics and the Department of Physics at Arizona State University. He is currently a Scialog Advanced Bioimaging fellow and directs the Quantitative Imaging and Inference Laboratory (qi2lab). Prior to joining Arizona State University, he was an assistant professor in the Departments of Physics and Pharmacology at the University of Colorado Denver Anschutz Medical Campus from 2013-2019. He received his Ph.D. in Physics from Colorado State University and was a postdoctoral fellow at the Center for Integrated Nanotechnologies and Center for Nonlinear Studies at Los Alamos National Laboratory from 2011-2013. The focus of qi2lab research is developing quantitative imaging and statistical inference tools to build predictive models of genetic regulation in multi-cellular systems.