"Dynamic Hydrogel Matrices: Biomaterials control in the Fourth Dimension"
Abstract: Methods for culturing mammalian cells in a biologically relevant context are increasingly needed to study cell and tissue physiology, expand and differentiate progenitor cells, and to grow replacement tissues for regenerative medicine. Two-dimensional culture has been the paradigm for in vitro cell culture; however, evidence and intuition suggest that cells behave differently when they are isolated from the complex architecture of their native tissues and constrained to petri dishes or material surfaces with unnaturally high stiffness, polarity, and surface to volume ratio. As a result, biologists are often faced with the need for a more physiologically relevant 3D culture environment, and biomaterials scientist see the opportunity to engineering custom 3D scaffolds with highly controlled chemical, biological and physical cues to serve this need. Further, the native extracellular matrix (ECM) is far from static, so ECM mimics must also be dynamic to direct complex cellular behavior, the so called fourth-dimension. In general, there is an un-met need for biomaterials that allow user-defined control over the spatio-temporal presentation of important signals, such as integrin-binding ligands, growth factor release, and biomechanical signals. Developing such hydrogel mimics of the ECM for 4D control of cellular processes is an archetypal engineering problem, requiring control of numerous properties on multiple time and length scales important for cellular functions. New materials systems have the potential to significantly improve our understanding of how cells receive information from their microenvironment and the role that these dynamic processes may play in controlling the stem cell niche to organoid development. This talk will illustrate recent efforts to advance hydrogel chemistries for 4D cell culture and regenerative biology, and how one can dynamically control biochemical and biophysical properties through orthogonal, photochemical click reaction mechanisms. One specific example will include the design of photoresponsive materials for the culture of adult intestinal stem cells and exogenously manipulating the matrix dynamics to direct symmetry breaking events and the evolution of deterministic organoid structures.
Bio: Kristi S. Anseth is the Tisone Distinguished Professor of Chemical and Biological Engineering and Head of Academic Leadership of the BioFrontiers Institute at the University of Colorado at Boulder, USA. Her research interests lie at the interface between biology and engineering where she designs new biomaterials for applications in drug delivery and regenerative medicine. Dr. Anseth is an elected member of the US National Academy of Engineering, the National Academy of Medicine, the National Academy of Sciences, the National Academy of Inventors, and most recently the American Academy of the Arts and Sciences. She is also a Fellow of the American Association for the Advancement of Science, American Institute for Medical and Biological Engineering, Society for Biomaterials, American Institute of Chemical Engineers, and Materials Research Society. Dr. Anseth currently serves on the Board of Directors of the American Institute of Chemical Engineers, Board of Trustees for the Gordon Research Conferences, on the Cell Biology Scientific Advisory Board of the Allen Institute. She is also an editor for Biomacromolecules and Progress in Materials Science.
"User-Programmable Hydrogel Biomaterials to Probe and Direct 4D Cell Fate"
Abstract: The extracellular matrix directs cell function through a complex choreography of biomacromolecular interactions in a tissue-dependent manner. Far from static, this hierarchical milieu of biochemical and biophysical cues presented within the native cellular niche is both spatially complex and ever changing. As these pericellular reconfigurations are vital for tissue morphogenesis, disease regulation, and healing, in vitro culture platforms that recapitulate such dynamic environmental phenomena would be invaluable for fundamental studies in stem cell biology, and towards engineering functional human tissue. In this talk, I will highlight our recent efforts using phototunable materials to modulate intricate cell fates with 4D control.
Bio: Dr. Cole A. DeForest is the Dan Evans Career Development Assistant Professor in the Departments of Chemical Engineering and Bioengineering, and a core faculty member of the Institute for Stem Cell & Regenerative Medicine at the University of Washington (UW) where he began in 2014. He received his B.S.E. degree from Princeton University in 2006, majoring in Chemical Engineering and minoring in Material Science Engineering and Bioengineering. He earned his Ph.D. degree under the guidance of Dr. Kristi Anseth from the University of Colorado in Chemical and Biological Engineering with an additional certificate in Molecular Biophysics. His postdoctoral research was performed with Dr. David Tirrell in the Divisions of Chemistry and Chemical Engineering at the California Institute of Technology. He has authored ~45 peer-reviewed articles, including as the corresponding author for those appearing in Nature Materials, Nature Chemistry, Advanced Materials, and Nature Reviews Materials. Dr. DeForest has received numerous research awards and honors including the Safeway Early Career Award (2018), NSF CAREER Award (2017), AIChE 35-Under-35 Award (2017), and the Presidential Distinguished Teaching Award (2016, UW’s highest teaching award, 1 awarded/year across all UW). His research has been supported through fellowships and grants from NSF, NIH, and the DOEd.
"What cell biological insights into cadherin regulation reveal about disease processes."
Abstract: Intercellular junctions are dynamically remodeled during morphogenesis and the control of tissue barriers. Modulation of the cadherin adhesive bond at the cell surface is important for these processes and we have developed a set of cadherin activating monoclonal antibodies to investigate them. Structural studies have begun to reveal potential mechanisms by which these mAbs activate adhesion. Activating mAbs to E-cadherin inhibit the metastasis of mammary tumor cells at multiple steps. By enhancing cell junctions and epithelial barrier function they also reduce inflammation in mouse models of inflammatory bowel disease. Thus, changes in cadherins at the cell surface contribute to disease.
Bio: Barry Gumbiner earned his Ph.D. in Neurosciences from the University of California San Francisco studying membrane protein trafficking in cells. As a postdoctoral fellow at the European Molecular Biology Laboratory he became interested in how cell junctions organize membrane domains, which led to his co-discovery of E-cadherin and its role in junction formation. He returned to UCSF as an Assistant Professor and set up his independent program to study the roles of cadherins and associated proteins, catenins, in embryonic development and tissue morphogenesis. This led to a career investigating mechanisms of cadherin mediated adhesion, cadherin-associated signaling pathways such as Wnt-b-catenin and the Hippo pathway, and their roles in tissue development and cancer. He has done this work at several institutions, including Memorial Sloan-Kettering Cancer Center and at the University of Virginia, where he was Chair of the Dept. of Cell Biology. In 2015 he moved to UW and Seattle Children’s to return to full time research. While continuing to explore mechanisms of cadherin function at the structural level, he has also investigated their roles in disease processes including metastasis and inflammatory diseases caused by deficits in cell junctions and barrier functions.
"Genome-wide mapping of protein-DNA interaction dynamics"
Abstract: Dr. Henikoff will describe his laboratory's CUT&RUN and CUT&Tag methods for chromatin profiling of small samples and single cells and selected applications to interesting biological problems.
Bio: Steven Henikoff received a BS in Chemistry from the University of Chicago, a PhD in Biochemistry and Molecular Biology from Harvard University and performed postdoctoral work in Zoology at the University of Washington. He is a member of the Basic Sciences Division at the Fred Hutchinson Cancer Research Center and an investigator of the Howard Hughes Medical Institute. He is also an affiliate professor of Genome Sciences at the University of Washington, a member of the National Academy of Sciences, a fellow of the American Association for the Advancement of Science, and co-Editor-in-Chief of the journal Epigenetics & Chromatin. His laboratory performs research on chromatin dynamics, transcriptional regulation and centromere maintenance, and develops experimental and computational tools for studying these processes.
"Better together: Insights into the clustering of ion channels"
Abstract: Voltage-gated ion channels are the basis of electrical excitability. It has been widely assumed that individual channels always behave independently with respect to voltage-activation, open probability, and facilitation. By combining super-resolution imaging, optogenetic tools, and electrophysiology we have found that L-type calcium channels undergo a functional clustering. We identified a new mechanism by which L-type calcium channels can physically couple and coordinate their openings to potentiate calcium influx. Now, we are studying how this coupling is regulated in the heart’s pacemaker and how aging is altering the way channels organize at the plasma membrane.
Bio: Dr. Moreno long term goal is to understand how the function of ion channels changes during the natural process of aging. Aging comes with a vast set of impairments, hearing loss, cardiac dysfunction, and hypertension, are only a few on the list. Most of these impairments are caused by a loss on the capacity of excitable cells to generate and/or propagate electrical signals. As ion channels are the basis of electricity in the body, Dr. Moreno’s team studies how aging affects ion channel function and how these changes can lead to the onset of aging-related pathologies. Her team combines electrophysiology and super-resolution imaging to study the age-related changes in ion channel function in one of the most electrical active tissues in the body, the pacemaker of the heart.
Dr. Moreno was born and grew up in Bogotá, Colombia. In 2012, Dr. Moreno received her doctoral degree in Biomedical Sciences with summa cum laude honors from the National Autonomous University of Mexico (UNAM). That same year, she joined Dr. Fernando Santana laboratory at the University of Washington to start her postdoctoral training. In 2017, she was awarded a K99-Pathway to the independence award by the National Institute on Aging. Dr. Moreno joined the Department of Physiology and Biophysics as an Assistant Professor on April 2019.
"Cytoskeletal innovations for sticking around"
Abstract: Giardia is an extracellular parasite that attaches to the host intestine to maintain infection. Remarkably, Giardia lacks all canonical actin binding proteins yet completes cytokinesis in just 50 seconds. During cytokinesis a lamellipodia-like membrane protrusion, known as the ventrolateral flange, grows in size while Giardia’s primary microtubule-based attachment organelle is disassembled. Parallel to lamellipodia formation we determined that actin and Giardia’s sole Rho GTPase, GlRac, are required for ventrolateral flange formation. Live cell imaging and functional studies indicate roles for the ventrolateral flange in parasite attachment and as a membrane reservoir that supports Giardia’s rapid cytokinesis.
Bio: Alex Paredez is an Associate Professor of Biology at the University of Washington. His laboratory studies the parasite Giardia which stands out as one of the most evolutionary divergent eukaryotes (from animals) that can be manipulated in the laboratory. His laboratory studies Giardia’s divergent actin cytoskeleton and differentiation into infectious cysts. The unifying goal of this work is to uncover constraining principles of biology as well as differences from host biology that can be leveraged for therapeutic development.
"Design of synthetic alternatives to biologics in medicine"
Abstract: Biologics, products produced from living organisms, have revolutionized treatment of disease. Examples of FDA-approved biologics include therapeutic proteins (e.g. blood clotting factors and antibodies), engineered viruses for gene therapy, and cell therapies. Biologics are addressing previous unmet medical needs, but are challenging to manufacture and therefore high in cost. In this talk, I will describe our efforts to develop synthetic alternatives to biologics used in medicine. In the first example, a multivalent polymer displaying a fibrin-binding peptide was developed as a synthetic alternative to recombinant proteins used in trauma medicine. The second example, a polymer that facilitates intracellular delivery of nucleic acids and peptides was synthesized based on design principles learned from adenoviral vectors.
Bio: Suzie H. Pun is the Robert F Rushmer Professor of Bioengineering, an Adjunct Professor of Chemical Engineering, and a member of the Molecular Engineering and Sciences Institute at UW. She is a fellow of the National Academy of Inventors (NAI) and the American Institute of Medical and Biological Engineering (AIMBE) and has been recognized with the Presidential Early Career Award for Scientists and Engineers in 2006 and as an AAAS-Lemelson Invention Ambassador in 2015. She serves as an Associate Editor for ACS Biomaterials Science and Engineering. Her research focus area is in biomaterials and drug delivery.
Suzie Pun received her B.S. in Chemical Engineering from Stanford University and her Ph.D. in Chemical Engineering from the California Institute of Technology working under the supervision of Professor Mark E. Davis. She also worked as a senior scientist at Insert Therapeutics/Calando Pharmaceuticals developing polymeric drug delivery systems before joining the Department of Bioengineering at University of Washington.
"Cooperation, competition and conviction in decision-making for motile cells"
Bio: Julie Theriot attended college at the Massachusetts Institute of Technology, earning dual B. S. degrees in physics and biology in 1988. She completed her Ph. D. in cell biology at the University of California at San Francisco in 1993, and then returned to Cambridge as a Whitehead Fellow at the Whitehead Institute for Biomedical Research. In 1997, she joined the faculty of the Stanford University School of Medicine, with appointments in the Department of Biochemistry and the Department of Microbiology & Immunology, and is currently an Investigator of the Howard Hughes Medical Institute. Her lab moved to the University of Washington in 2018, and she also has an appointment at the Allen Institute for Cell Science. The experimental work of her research group focuses on quantitative measurement of the dynamic and mechanical behavior of structural components in living cells, exploring the molecular and biophysical mechanisms of various forms of cell motility and shape determination across a variety of eukaroytic and bacterial cell types. Theriot has won numerous awards for her research, including the David and Lucile Packard Foundation Fellowship for Science and Engineering and the John D. and Catherine T. MacArthur Foundation Fellowship. She has also received multiple teaching awards from both M. D. and Ph. D. students at Stanford. She is a coauthor of the textbook Physical Biology of the Cell.
"Bending the rules of organelle biogenesis: views from a highly specialized cell"
Abstract: Germ cells are typically admired for their totipotency, their natural ability during development or demonstrated capacity after external manipulation to give rise to all differentiated cells in an organism. Perhaps less widely appreciated are the remarkable changes that preserve nuclear totipotency, but profoundly alter the composition and morphology of germ cell organelles to enable mature gametes to participate in fertilization and support the initiation of embryogenesis. This talk will describe the cell biological lessons learned from studying how developing spermatids “bend” the conventional rules of organelle morphogenesis and exploit specialized molecules to produce the highly specialized sperm cell.
Bio: Barbara Wakimoto is a Professor of Biology, an Adjunct Professor of Genome Sciences, and a member of the Molecular and Cellular Biology Program at the University of Washington. Her training in developmental biology began as an undergraduate at Arizona State University and continued as a graduate student at Indiana University where she worked on defining the genes in the Antennapedia Complex of Drosophila. As a Helen Hay Whitney postdoctoral fellow, she studied gene expression during Drosophila oogenesis at the Carnegie Institution. She joined the UW faculty as an Assistant Professor and Searles Scholar in 1985, was a Washington Research Foundation Professor of Basic Biological Sciences in 2005-2007 and was named a AAAS Fellow in 2007. Her current research interests center on discovering molecules and pathways required for sperm formation, sperm function during fertilization, and paternal effects on early embryogenesis using a combination of genetic, genomic and cell biological approaches.