Cell biology and the "real world".

Abstract

Molecular Biology of the CellVol. 27, No. 6 ASCB Annual Meeting HighlightFree AccessCell biology and the “real world”Craig Blackstone and Lisa D. BelmontCraig Blackstone*Address correspondence to: Craig Blackstone (E-mail Address: [email protected]), Lisa D. Belmont (E-mail Address: [email protected]).Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892Search for more papers by this author and Lisa D. Belmont*Address correspondence to: Craig Blackstone (E-mail Address: [email protected]), Lisa D. Belmont (E-mail Address: [email protected]).Discovery Oncology, Genentech, South San Francisco, CA 94080Search for more papers by this authorPublished Online:13 Oct 2017https://doi.org/10.1091/mbc.E15-11-0764AboutSectionsView PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail The “Applications of Cell Biology in the Real World” Minisymposium comprised two full sessions. Although the topic was overwhelmingly broad, several central themes emerged. Disease mechanisms and therapeutics permeated many of the talks, with an array of different, and often unexpected, experimental systems, new analytical tools, and model organisms also discussed.Cancer was a focus of a number of presentations, with new approaches addressing long-standing problems. Lisa Belmont (Genentech) discussed strategies for targeting the tumor suppressor BRG1, an ATP-dependent helicase frequently mutated in cancer, which is part of the BAF complex that remodels chromatin. Based on synthetic lethal interaction identifications, the data she discussed suggest that inactivating related helicases might be a promising strategy. Bert Gough (University of Pittsburgh) described methods for exploiting (rather than bemoaning) the broad heterogeneity among different cell types to facilitate drug discovery, focusing on investigations of signaling heterogeneity in the IL-6-activated STAT3 pathway and describing novel tools such as a “heterogeneity browser.” Hirofumi Matsui (University of Tsukubu) discussed the development of optical cell separation and culture systems that use photodegradable hydrogels, photoirradiation, and cell picking to separate cells based on morphological criteria, along with the development of automated systems useful for the study of cancer cells.Another overarching theme encompassed cell death, aging, and neurodegeneration, with numerous new tools and approaches described here as well. Vlad Denic (Harvard University) described his studies of the essential protein heat shock factor 1 (Hsf1) in yeast. Because Hsf1 inactivation causes protein aggregation, he used an “anchor-away” approach to acutely deplete Hsf1 in the presence of rapamycin and found that heat shock protein family members, in particular Hsp70 and Hsp90, were necessary and sufficient to allow cells to survive in the absence of Hsf1. Marc Hammarlund (Yale University) spoke about axon regeneration, using pulsed-laser axotomy in Caenorhabditis elegans as an in vivo model and emphasizing the critical role of inhibiting poly(ADP-ribosylation) in stimulating regeneration. Jonny Nixon-Abell (University College London and National Institutes of Health) used emerging superresolution imaging approaches to clarify the distinct morphologies and dynamics of peripheral ER tubules and noted that important disorders such as hereditary spastic paraplegia are linked to proteins involved in ER morphology. Grazing incidence illumination (GI)-SIM and lattice light sheet-point accumulation for imaging in nanoscale topography (LLS-PAINT) were used to reveal novel, ultrafast dynamism in the peripheral ER and further indicated that many structures classically considered peripheral sheets are instead dense tubular matrices. Christopher Medina (University of New Mexico) spoke about kinesin-1 deficiency and imaging in living mouse brain, presenting techniques such as tracing circuitry in vivo using magnetic resonance imaging after focal manganese injection. These techniques were able to show altered axonal transport in vivo in hippocampal-to–basal forebrain memory circuits, pathogenically implicating decreased synaptic vesicle replacement in active synapses. Moving to injury repair, Virginia Ayres (Michigan State University) identified nanoscale cues for regenerative neural cell systems, specifically for polyamide nanofiber scaffolds used in spinal cord injury repair, using specially adapted atomic force microscopy for the cues and superresolution imaging for reactive astrocyte protein responses.A variety of neurodegenerative disorders also took center stage. Aditya Venkatesh (University of Massachusetts) spoke about retinitis pigmentosa (RP), an inherited photoreceptor degenerative disorder (with many known mutated genes in rod genes) that results in blindness from secondary loss of retinal cones. Cone survival depends on mTORC1, which has an essential role in clearance of autophagic aggregates. Activating mTORC1 by reducing TSC1 promotes long-term cone survival, prefiguring therapeutic potential to prolong vision in RP. Alzheimer’s disease was the topic of several talks. Rylie Walsh (Brandeis University) investigated Drosophila neuromuscular junctions to describe how perturbations in the retromer protein complex cause changes in amyloid precursor protein (APP)–positive exosome levels. Neuronal retromer was able to rescue APP accumulation in a retromer mutant. Natalya Gertsik (Weill Cornell Medical College) discussed how γ-secretase inhibitors and modulators might be useful for Alzheimer’s disease treatment via their inducement of distinct conformational changes within the active sites of γ-secretase and signal peptide peptidase that she identified by photophore walking. Risa Broyer (University of California, San Diego) leveraged the cell biology of metabolic enzymes to uncover new insights into orphan genetic diseases affecting metabolic pathways, emphasizing studies of PRPP synthase, where filament formation may be involved in pathogenesis.Infections and vascular disorders are also prominent themes in medicine, and cell biology is enlightening these areas. Meron Mengistu (University of Maryland) spoke about HIV vaccine development, using three-dimensional dSTORM microscopic visualization of vulnerable sites exposed on cell-bound HIV to inform better therapy. Robert Cooper (University of California, San Diego) described how neighbor killing via the type VI secretion system enables high-efficiency, cross-species acquisition of antibiotic resistance via “gene snatching” in competent Acinetobacter bacteria—a strain of serious threat to hospitalized patients. Vascular disease is always of interest, and Akira Sawaguchi (University of Miyazaki) spoke about the dynamics of thrombus formation in mouse testicular surface vein using a new vascular mapping method for correlative light and electron microscopy (CLEM) in vivo, revealing detailed structure of the thrombus. Larry Lemanski (Texas A&M University) described how cardiac-inducing RNAs help differentiation of nonmuscle cells from muscle cells, which might play a role in helping those with myocardial infarction recover function.Sometimes extreme examples can teach us fundamental biology, relevant beyond human disease. Thomas Boothby (University of North Carolina) introduced many participants to tardigrades, one of the most resilient survivors in existence, which tolerate a very broad range of temperatures, even that of outer space, and desiccation. Specific genes are up-regulated and required for survival when desiccated. The proteins encoded by these genes can form bioglasses that stabilize proteins upon desiccation. Understanding such mechanisms may lead to creation of drought-resistant crops and heat-stable vaccines. Finally, Shiva Razavi (Johns Hopkins University) spoke about reconstitution of chemotaxis in giant unilamellar vesicles, employing a rapamycin-induced dimerization system (FKBP and FRB).Cell biology studies affect a wide range of diseases and other basic cellular questions, with new tools leading the way. Cells are the basic unit of life, and the presentations in this minisymposium highlight how broad and fundamental cellular insights are for understanding and improving life.FOOTNOTESDOI:10.1091/mbc.E15-11-0764FiguresReferencesRelatedDetails Vol. 27, No. 6 March 15, 2016873-1050 Metrics Downloads & Citations Downloads: 98 History Information© 2016 Blackstone and Belmont. This article is distributed by The American Society for Cell Biology under license from the author(s). 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