Speakers, in order of appearance
Talk title: "Heterochromatin through the lens of phase-separation"
Bio: Dr. Narlikar obtained her Ph.D. in Chemistry at Stanford University under the mentorship of Dr. Daniel Herschlag and carried out postdoctoral research at Harvard Medical School under the mentorship of Dr. Robert Kingston. She has been a faculty member in the Department of Biochemistry and Biophysics at UCSF since 2003. She is an expert in the fields of epigenetic regulation and genome organization. Dr. Narlikar studies how the folding and compartmentalization of our genome is regulated to generate the many cell types that make up our body. Her laboratory has pioneered the application of sophisticated biophysical approaches to study the mechanisms of macromolecules that regulate genome organization. Through these studies they are learning (i) how nanoscale molecular motors use chemical energy to cause mechanical disruptions in the packaged genome, (ii) that the smallest unit of genome folding, a nucleosome, acts akin to a dynamic receptor rather than a static packaging unit and, (iii) that liquid-liquid phase separation processes can help organize and sequester large regions of the genome. These types of discoveries from the Narlikar laboratory are changing textbook descriptions of genome packaging and suggesting new avenues to tackle diseases caused by defects in genome organization.
Dr. Narlikar enjoys teaching and mentoring graduate students. She believes that kindling the fire of curiosity within graduate students and consistently supporting their initiative brings out the best in them.
Dr. Narlikar’s scientific work has been recognized by different awards during the course of her faculty career. These include the Beckman Young Investigator Award (2006), the Leukemia and Lymphoma Society Scholar Award (2008), the Outstanding Faculty Mentorship Award by the UCSF Graduate Students Association (2011), the Deleage Prize awarded by the Deleage foundation (2017), the Glenn Award for Research in Biological Mechanisms of Aging (2018), and the Distinguished Alumnus Award from the Indian Institute of Technology, Mumbai (2018). Since 2017, Professor Narlikar has been appointed to the Lewis and Ruth Cozen Chair I.
Bio: Alexandra Zidovska is an Assistant Professor of Physics at the Center for Soft Matter Research in the Physics Department at New York University. She received her PhD in 2008 from University of California, Santa Barbara after she completed her undergraduate studies and M.Sc. at Technical University of Munich, Germany. She pursued her postdoctoral studies at Harvard University. Prof. Zidovska held prestigious Damon Runyon Cancer Research Fellowship 2010-12, was named Whitehead Fellow 2016 and is a recipient of the National Institutes of Health Pathway to Independence Award, National Science Foundation CAREER Award and Michele Auger Award 2020. Her current research uses approaches from soft matter physics and polymer physics to study the cell nucleus and its constituents, such as the genome and subnuclear bodies, in particular their dynamics and spatial organization. She is also passionately engaged in causes related to diversity and inclusion in physics and related sciences. Her lab has an impressive record of recruiting, training and promoting women scientists across all levels, and Prof. Zidovska is founder and faculty leader of a new group,NYU Women in Physics dedicated to providing a more welcoming and stimulating environment for women and those from other underrepresented groups in physics.
Bio: Arjun went to UC Berkeley, where he majored in math and physics, earned his PhD in math from the Courant Institute at NYU, and did his postdoctoral training at MIT before joining the faculty at Penn in 2010. He is currently a Professor of Bioengineering and Professor of Genetics. His research focus is on the developed experimental techniques for making highly quantitative measurements in single cells and models for linking those measurements to cellular function. His ultimate goal is to achieve a quantitative understanding of the molecular underpinnings of cellular behavior.
Bio: Dr. Buchwalter Cool's laboratory is focused on understanding the cell biology of the genome. They focus on three main thematic areas: (i) defining how the nuclear lamina promotes establishment and maintenance of cell-type-specific gene expression programs; (ii) determining how regulation of the nuclear periphery by protein turnover shapes its functions; and (iii) exploring how disruption of the nuclear lamina promotes aging and disease. They integrate approaches from cell biology, molecular biology, genomics, and proteomics to achieve these goals.
Talk title : Such a lot of genome to see…
Abstract: Ting (C.-ting) Wu is a Professor of Genetics at Harvard Medical School, where she also directs the Consortium for Space Genetics and the Personal Genetics Education (pgEd.org) Project. Her group focuses on chromosome organization and behavior in the context of gene regulation and inheritance, and this emphasis has led them to investigate a diversity of topics, ranging from the function and structure of paired homologous sequences to the organization of centromeres and the potential of sequence ultraconservation to contribute to genome stability and evolution. Their studies have used genetic and molecular genetic tools, haplotype-resolved Hi-C, and computational approaches. Her laboratory also develops and applies technologies for visualizing the genome, aiming to augment genomic coverage and genomic and optical resolution at conventional and super resolution (Oligopaints, Hi-FISH, HOPs, OligoSTORM, OligoDNA-PAINT, JEB, and OligoFISSEQ). The Wu laboratory also houses pgEd, which works to promote public awareness and dialog about genetics and genetic technologies across all communities by working in classrooms, providing curricula and teacher training, running Congressional briefings, and working with the film and television industry.
In vivo analysis of nuclear mechanics and mechanotransduction
Abstract: Daniel Starr and GW Gant Luxton are studying a protein complex known as LINC, whose role is to physically connect the nucleus to the cell’s interior scaffolding system, otherwise known as the cytoskeleton. The LINC complex is involved in translating mechanical forces inside the cell into chemical signals, but how that translation happens and how it is regulated remains unknown. In many diseases, including cancer, heart disease, muscular dystrophy and neurodegenerative disorders, cells lose the ability to correctly translate these cues. Starr and Luxton are leading a team to study how LINC complexes are formed in the cell, how they organize and influence structures within the nuclei known as nucleoli, and how they regulate the cell’s mechanical properties.
Bio: G.W. Gant Luxton is an Associate Professional Researcher/Principal Investigator of Molecular and Cellular Biology at the University of California, Davis. His laboratory investigates the role of the nucleus during mechanotransduction, or the fundamental ability of cells to sense and respond to mechanical forces. Their lens on nuclear mechanotransduction is the conserved nuclear envelope-spanning molecular bridge known as the linker of nucleoskeleton and cytoskeleton (LINC) complex, which mechanically integrates the nucleus with the cytoskeleton and consequently the extracellular environment. They use a suite of cutting-edge biophysical, cell biological, quantitative imaging, and synthetic biological approaches to investigate the assembly of functional LINC complexes as well as how LINC complex dysfunction contributes to human neuromuscular disease pathogenesis.
Daniel Starr is a professor of Molecular and Cellular Biology at the University of California, Davis. His laboratory studies how nuclei move, and then anchor to, a specific part of a cell throughout development. The Starr Lab focuses on the molecular mechanisms of KASH and SUN proteins in the nuclear envelope to determine how the nucleus connects to the cytoskeleton, primarily using C. elegans as a model system to better understand nuclear positioning in a developmental context. The lab team answers fundamental questions in cell and developmental biology, including how motors target to the nuclear envelope and how the activities of motors are switched throughout development, how the nuclear lamina is connected to the nuclear envelope, how actin filaments move nuclei, and how molecular forces are transferred across the nuclear envelope. All of these mechanisms have been shown to be conserved across eukaryotes and defects in these processes lead to a variety of neuromuscular diseases. The Starr Lab is particularly interested in how these mechanisms are regulated to squeeze nuclei through constricted spaces and how this relates to development and cancer metastasis.
New models for nuclear homeostasis: integrating force, flow and pressure
Abstract: How does the nucleus keep its size and shape? Megan King and Simon Mochrie are leading a collaborative team to study the physical and molecular forces that maintain the correct size of our cells’ largest organelle, the nucleus. For reasons that have long remained mysterious, the nucleus is always scaled to take up a certain percentage of a healthy cell’s volume. This measured scaling is often thrown out of whack in diseases such as cancer, but the mechanisms underlying its maintenance and why those mechanisms fail in disease remain unclear. The researchers hypothesize that nuclear pore complexes, transport channels which perforate the nuclear membranes, regulate the organelle’s size by maintaining a set level of tension and pressure.
Bio: Dr. Megan King is an Associate Professor in the Departments of Cell Biology at Yale School of Medicine and Molecular Cell and Developmental Biology at Yale University. She received her B.A. in Biochemistry from Brandeis University working with Dr. Susan Lowey on the functions of skeletal myosin light chains and her Ph.D. in Biochemistry and Molecular Biophysics from the University of Pennsylvania working with Dr. Mark Lemmon on dynamin and its antiviral cousin, MxB, which she found docks at nuclear pore complexes and influences nuclear transport. During her postdoctoral training with Dr. Günter Blobel at Rockefeller University, Dr. King discovered new mechanisms for the targeting and function of integral inner nuclear membrane proteins. Her work uncovered a critical physical network comprised of chromatin inside the nucleus, nuclear envelope membrane proteins, and the cytoplasmic cytoskeleton. Since founding her own group at Yale in 2009, Dr. King has continued to investigate the broad array of biological functions that are integrated at the nuclear envelope. Her group was the first to demonstrate that chromatin and its tethering to the nuclear envelope plays a critical role in determining the mechanical stiffness of nuclei. Her team has also made key contributions to our understanding of genome integrity pathways and mechanotransduction through the LINC complex. Dr. King was named a Searle Scholar in 2011 and is a recipient of the NIH New Innovator Award.
Simon Mochrie is a Professor of Physics and of Applied Physics at Yale University, where he studies the physics of living materials. The recent focus of his research has been to bring simple theoretical and computational approaches to elucidate chromatin organization and dynamics, and to compare the resultant predictions to experimental data. In other projects, he used small-angle x-ray scattering on single insect scales to identify ordered photonic nanostructures, which insects grow by exploiting the self-organizing propensity of cellular lipid-bilayer membranes, and he showed that the folding/unfolding thermodynamics of repeat proteins can be quantitatively described by the classical one-dimensional Ising model. Throughout his career, an important feature of Simon’s research has been the introduction of novel methods, analyses, and approaches. Before engaging with biological physics, he invented, developed and exploited x-ray photon correlation spectroscopy (XPCS) to characterize the slow dynamics of polymeric and colloidal systems on shorter length scales than possible optically. This work led to the Advanced Photon Source’s Arthur H. Compton Award in 2009 and has motivated the implementation of beamlines for XPCS at synchrotron facilities around the world. He earned a BA from the University of Oxford and a PhD in Physics from the Massachusetts Institute of Technology, where he studied phase transitions in a number of systems that realize low-dimensional behavior. He then became a Member of Technical Staff at AT&T Bell Laboratories, before returning to MIT as faculty. He moved to Yale in 2000.
Katharine Ullman, Ph.D. | University of Utah & Maho Niwa, Ph.D. | University of California San Diego
Nuclear-endoplasmic reticulum communication during normal remodeling and pathological alteration of these organelles
Abstract: Katharine Ullman and Maho Niwa are leading a research project to investigate the interactions between the nucleus and one of its neighboring organelles, the endoplasmic reticulum. These two cellular structures are joined at the hip — together, their outer borders form one continuous, folding membrane. Despite their close connections, these structures are often studied independently, and their influences on each other beyond transcription remain poorly understood. Ullman and Niwa plan to study their interactions by inducing stress on either the nucleus’s border, also known as the nuclear envelope, or the endoplasmic reticulum and observing the effects of that stress on the other organelle. They will also ask how interactions between the nucleus and endoplasmic reticulum affect cell division, during which these organelles undergo major structural changes. Their findings could shed light on basic cell biology and diseases like cancer where alterations to nuclear structure and demands on endoplasmic reticulum function place heightened pressure on their crosstalk.
Bio: Katharine Ullman, Ph.D., is a Professor of Oncological Sciences and Huntsman Cancer Institute Investigator at the University of Utah. She studied biochemistry, molecular biology and cell biology at Northwestern University, graduating with a B.A. in 1986 and then attended Stanford University for graduate school, where she earned her doctoral degree working with Dr. Gerald Crabtree. She did postdoctoral training in the lab of Dr. Douglass Forbes at the University California San Diego before joining the faculty at the University of Utah in 1998. Ullman served several years as a Cancer Center Program leader and currently is the associate dean of the University of Utah Graduate School. Past honors include a Burroughs Wellcome Career Award and a Leukemia and Lymphoma Scholar Award. Her lab focuses on elucidating molecular steps of nuclear assembly and their coordination with disassembly of the mitotic spindle apparatus, as well as building further on the novel connection her lab discovered between the function of particular nuclear pore proteins and the regulation of cytokinesis. Collaborating with Dr. Maho Niwa opens exciting new opportunities to study how the architecture and function of the nucleus and another major cellular organelle, the endoplasmic reticulum, are interconnected.
Maho Niwa, Ph.D., is a Professor of Molecular Biology in the Division of Biological Sciences at the University of California San Diego. Dr. Niwa received her Ph.D. from Baylor College of Medicine with Dr. Susan Berget, pioneering how exons are molecularly chosen from the sea of intron sequences present in each human gene. Dr. Niwa joined Dr. Peter Walter’s laboratory at the University of California, San Francisco, where she received postdoctoral training, supported by a Jane Coffin Childs postdoctoral fellowship. Dr. Niwa started her own laboratory at UCSD in 2002. Her past honors include a Searle Foundation Faculty Scholar award, and two American Cancer Society Faculty Scholar awards. Research in Dr. Niwa’s laboratory focuses on understanding how the endoplasmic reticulum (ER), the gateway to the secretory pathway and source of most lipids and approximately one-third of all cellular proteins, regulates these functional demands in response to distinct environmental, developmental, or disease cues. This is achieved by studying a stress signaling pathway called the Unfolded Protein Response (UPR). Dr. Niwa studies how mis-regulation of the UPR leads to human diseases, ranging from asthma to cancer. Her lab also discovered a cell cycle checkpoint in yeast that ensures that all dividing cells receive both functionally correct and spatially sufficient ER during the cell cycle. This was one of the first cell cycle checkpoints found to regulate the inheritance of the cytoplasmic components and is known as the ER stress surveillance (ERSU) checkpoint. In yeast, ERSU halts ER inheritance, leading to a block of cell division until the ER can be repaired. Recently, the Niwa lab made seminal discoveries in both yeast and mammals that ER stress induces specific sphingolipids and these in turn act as key inducers for the ER cell cycle checkpoint. In collaboration with Dr. Katherine Ullman (Huntsman Cancer Institute, U. Utah), she plans to investigate how the ER communicates with the architecture and function of the nucleus, unleashing a new exciting area of cell biology.
Talk title: Cell wound repair: Dealing with life’s daily traumas
Bio: Susan Parkhurst is a Professor in the Basic Sciences Division at the Fred Hutchinson Cancer Research Center and an Affiliate Professor in the Department of Biology at the University of Washington. She received a BA in Biology from the Johns Hopkins University and earned her PhD in Developmental Biology in the lab of Dr. Victor Corces also at the Johns Hopkins University studying genetic suppression/chromatin boundary elements. She did her postdoctoral work with Dr. David Ish-Horowicz at the Imperial Cancer Research Fund in Oxford UK (now Cancer Research UK) studying the role of transcriptional repressors in embryonic segmentation and sex determination, and then with Dr. Howard Lipshitz at Caltech continuing her studies of transcriptional repressors. She then set up her lab at Fred Hutch where her group uses multidisciplinary approaches to study dynamic membrane-cortical cytoskeleton interactions regulating normal developmental events and the consequences of this regulation going awry. Their current efforts are divided between studies investigating the components/machineries, signals, and events that govern cell wound repair, and mechanisms underlying Nuclear Envelope Budding, a process wherein large macromolecular complexes are packaged within the nucleus then extruded through the nuclear membranes.
Bio: Dr. Applewhite is an Associate Professor in the Biology Department at Reed College in Portland, OR. Prior to Reed, he was a Postdoctoral Fellow at the Biology Department at the University of North Carolina in Chapel Hill, NC. He received my Ph.D. in Cell and Molecular Biology at Northwestern University in Chicago, IL in 2007 and received a B.S. in Biology at the University of Michigan in Ann Arbor, MI in 2002. The central goal of his research—To understand the regulation of the cytoskeleton. Just as we have bones and muscles that give our bodies shape and allow us to move, cells have analogous structures known as the cytoskeleton. The cytoskeleton is composed of three filament networks, the actin, microtubule, and intermediate filament cytoskeletons. All three networks are composed of polymers that polymerize to form larger networks. It is these networks, that are dynamic and highly regulated, that give cells their shape and allow them to move. The cytoskeleton is therefore critical to the shape change or morphogenesis cells undergo during development, immune functions, the path finding that developing neurons undergo when establishing connections, and in cases where the cytoskeletal machinery works aberrantly, metastasis during tumorgenesis.
Cell Science Junior Fellow
Bio: David Van Valen is an Assistant Professor in the Division of Biology and Bioengineering at the California Institute of Technology. His research group’s long-term interest is to develop a quantitative understanding of how living systems process, store, and transfer information, and to unravel how this information processing is perturbed in human disease states. To that end, his group leverages—and pioneers—the latest advances in imaging, genomics, and machine learning to produce quantitative measurements with single-cell resolution as well as predictive models of living systems. Prior to joining Caltech, he studied mathematics (BS 2003) and physics (BS 2003) at the Massachusetts Institute of Technology, applied physics (PhD 2011) at the California Institute of Technology, and medicine at the David Geffen School of Medicine at UCLA (MD 2013).
Cell Science Junior Fellow
Bio: Dr. Kampmann is an Associate Professor in the UCSF Department of Biochemistry and Biophysics and the Institute for Neurodegenerative Diseases, and an Investigator at the Chan Zuckerberg Biohub. He received his BA in Biochemistry from Cambridge University and his PhD in Biophysics/Cell Biology from Rockefeller University. The goal of Dr. Kampmann’s research is to elucidate cellular mechanisms of brain disease and to develop new therapeutic strategies. He co-developed the CRISPRi and CRISPRa screening technologies, and his lab has pioneered CRISPR-based functional genomics in cell types derived from induced pluripotent stem cells (iPSCs). A major focus is the investigation of neurodegenerative diseases in human iPSC-derived neurons, astrocytes, and microglia, and 3D assembloids/organoids. Dr. Kampmann was named an NIH Director’s New Innovator, an Allen Distinguished Investigator, a Chan Zuckerberg Biohub Investigator, and he received the CZI Ben Barres Early Career Acceleration Award.