Cell biology and the " real world ". Blackstone, C. and Belmont, L. D Molecular Biology of the Cell, 27:878--879.
doi  abstract   bibtex   
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 de-velopment 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 devel-opment 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 de-scribed 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 axot-omy 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 imag-ing 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 kine-sin-1 deficiency and imaging in living mouse brain, presenting tech-niques 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 de-creased 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 super-resolution imaging for reactive astrocyte protein responses. A variety of neurodegenerative disorders also took center stage. Aditya Venkatesh (University of Massachusetts) spoke about retini-tis pigmentosa (RP), an inherited photoreceptor degenerative disor-der (with many known mutated genes in rod genes) that results in blindness from secondary loss of retinal cones. Cone survival de-pends on mTORC1, which has an essential role in clearance of au-tophagic aggregates. Activating mTORC1 by reducing TSC1 pro-motes 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 neu-romuscular 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 modula-tors might be useful for Alzheimer's disease treatment via their in-ducement 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 path-ways, emphasizing studies of PRPP synthase, where filament forma-tion 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 devel-opment, using three-dimensional dSTORM microscopic visualization
@article{blackstone_cell_????,
	title = {Cell biology and the " real world "},
	volume = {27},
	issn = {1059-1524},
	doi = {10.1091/mbc.E15-11-0764},
	abstract = {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 de-velopment 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 devel-opment 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 de-scribed 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 axot-omy 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 imag-ing 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 kine-sin-1 deficiency and imaging in living mouse brain, presenting tech-niques 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 de-creased 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 super-resolution imaging for reactive astrocyte protein responses. A variety of neurodegenerative disorders also took center stage. Aditya Venkatesh (University of Massachusetts) spoke about retini-tis pigmentosa (RP), an inherited photoreceptor degenerative disor-der (with many known mutated genes in rod genes) that results in blindness from secondary loss of retinal cones. Cone survival de-pends on mTORC1, which has an essential role in clearance of au-tophagic aggregates. Activating mTORC1 by reducing TSC1 pro-motes 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 neu-romuscular 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 modula-tors might be useful for Alzheimer's disease treatment via their in-ducement 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 path-ways, emphasizing studies of PRPP synthase, where filament forma-tion 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 devel-opment, using three-dimensional dSTORM microscopic visualization},
	journal = {Molecular Biology of the Cell},
	author = {Blackstone, Craig and Belmont, Lisa D},
	pages = {878--879}
}
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