Speaker: Susanne Rafelski, PhD 

Title: Integrated intracellular organization and its variations in human iPS cells 

Abstract: Understanding how a subset of expressed genes dictates cellular phenotype is an enormous challenge due to the large numbers of molecules, their combinatorics, and the plethora of cellular behaviors they determine. We reduced this complexity by focusing on cellular organization, a key readout and driver of cell behavior, at the level of major cellular structures representing distinct organelles and functional machines and generated the “hiPSC Single-Cell Image Dataset” with over 200,000 live cells in 3D spanning 25 major cellular structures. The scale and quality of this dataset permitted the creation of a generalizable analysis framework to convert raw image data of cells and their structures into dimensionally reduced, human-interpretable quantitative measurements and to facilitate data exploration. This framework embraces the vast cell-to-cell variability observed within a normal population, facilitates the integration of cell-by-cell structural data, and permits quantitative analyses of distinct, separable aspects of organization within and across different cell populations. We found that the integrated intracellular organization of interphase cells was robust to the wide range of cell shape variations in the population, that the average locations of some structures became polarized in cells at the edges of colonies while maintaining the “wiring” of their interactions with other structures, and that, in contrast, structure location changes during early mitotic reorganization were accompanied by changes in their wiring.

Bio: Susanne Rafelski is the Deputy Director of the Allen Institute for Cell Science, which aims to understand the principles by which human induced pluripotent stem cells (hiPSC) establish and maintain robust dynamic localization of cellular structures, and how cells transition between states during differentiation and disease. She graduated from the University of Arizona with undergraduate degrees in Biochemistry and Molecular & Cellular Biology with an additional emphasis in Mathematics before moving to Stanford University, where she earned a PhD. in Biochemistry for work with Julie Theriot on the actin-based motility of the bacterial pathogen, Listeria monocytogenes. For her postdoctoral research, she first worked with Garry Odell at the Center for Cell Dynamics at the Friday Harbor Labs (University of Washington) where she learned iterative experimental-computational modeling approaches. She then initiated her research program on mitochondrial structure-function as a postdoc, working with Wallace Marshall at UCSF, where she developed 3D microscopy and image analysis methods to quantify mitochondrial morphology and applied these to investigate mitochondrial size control regulation. Susanne moved to an Assistant Professor position in the Department of Developmental and Cell Biology, the Department of Biomedical Engineering, and the Center for Complex Biological Systems at UC Irvine where her lab extended this work, studying principles of intracellular organization, via the control of size, topology, and function of mitochondrial networks in budding yeast and mammalian cells. Susanne started at the Institute in 2016 as the Director of Assay Development where she contributed to developing and implementing the overall scientific direction of the Institute, which she now continues to guide.

Host: Gaudenz Danuser, PhD

A reception will be held after the seminar to allow more interaction with the speaker.