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SUMMARY:RNA Innovation Seminar: Nils G. Walter\, Ph.D.\, Co-Director\, U-M Center for RNA Biomedicine
DESCRIPTION:“Single molecules come into focus: From bacterial riboswitches to mammalian cellular phase separation”\nNils G. Walter\, Ph.D.\nCo-Director\,\nU-M Center for RNA Biomedicine\nFrancis S Collins Collegiate Professor of Chemistry\, Biophysics\, and Biological Chemistry\,\nU-M LSA \n  \n  \nAbstract:\nAt least 75% of the 3 billion base pairs of the human genome are transcribed into RNA\, but the vast majority of these transcripts do not code for proteins but rather for “non-coding” RNAs (ncRNAs)\, many of which remain uncharacterized in terms of their structure and function. Currently\, more than 80\,000 unique ncRNAs have been identified in human cells alone\, suggesting that for a long time we have underestimated the intricacies involved in human genome maintenance\, processing\, and regulation by neglecting this far-reaching “RNA World.” Nature and modern nanotechnology likewise employ nanoscale RNA machines that self-assemble into structures of complex architecture and functionality. Fluorescence microscopy offers a non-invasive tool to probe\, dissect and ultimately control these nanoassemblies in real-time. In particular\, single molecule fluorescence resonance energy transfer (smFRET) allows us to measure distances at the 2-8 nm scale\, whereas complementary super-resolution localization techniques based on Gaussian fitting of imaged point spread functions (PSFs) measure distances in the 10 nm and longer range. Encapsulating the power of these recent technical advances\, we have combined single-molecule and biochemical approaches to show that a central\, adaptable RNA helix in the widespread manganese-sensing riboswitch functions analogous to a molecular fulcrum to integrate disparate signals for finely balanced bacterial gene expression control. We posit that many more examples of such intimate structural and kinetic coupling between RNA folding and gene expression remain to be discovered\, leading to the exquisite regulatory control and kinetic proofreading enabling all life processes. On the more applied side\, we are developing tools to study the liquid-liquid phase separation of RNA-protein granules involved in human pathologies. \nBiography:\nNils G. Walter (photo by Michigan Photography) is currently the Francis S. Collins Collegiate Professor of Chemistry\, Biophysics\, and Biological Chemistry in the College of Literature\, Science and the Arts of the University of Michigan in Ann Arbor\, Michigan. He cofounded and currently co-directs the Center for RNA Biomedicine at Michigan\, now developing a thrust in RNA Therapeutics. His research interests focus on gene regulation by noncoding RNAs through the lens of single molecule techniques and applications in drug discovery. \nIn-person: BSRB\, Kahn Auditorium / hybrid link\n \nLinks to learn more about Nils Walter and his work:\nNils Walter’s Faculty Page\nNils Walter’s Lab Page\nNils Walter’s Wikipedia Page \n 
URL:https://rna.umich.edu/events/rna-innovation-seminar-nils-g-walter-ph-d-co-director-u-m-center-for-rna-biomedicine/
LOCATION:BSRB – Kahn Auditorium
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LAST-MODIFIED:20241111T164056Z
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SUMMARY:RNA Innovation Seminar: Jennifer E. Phillips-Cremins\, Ph.D.\, Associate Professor and Dean's Faculty Fellow\, Biomedical Engineering and Human Genetics\, Penn Epigenetic Institute
DESCRIPTION:“The Science of Connections: Bridging chromatin folding\, synaptic plasticity\, and neurophysiology”\nJennifer E. Phillips-Cremins\, Ph.D.\nAssociate Professor and Dean’s Faculty Fellow\,\nBioengineering and Genetics\,\nPenn Epigenetics — University of Pennsylvania \nIn-person: Kahn Auditorium\, BSRB | Hybrid link \nAbstract:\nThe Cremins Laboratory works at the spatial biology-technology interface to investigate the structure-function relationship of connections in the brain across the scales of chromatin\, synapses\, and circuits in normal neurophysiology and in neurological disorders. We have thus far focused in the nucleus on creating kilobase-resolution maps of higher-order folding of the chromatin fiber and understanding how classic epigenetic modifications work through long-range connections to govern genome function in neurodevelopment. We have developed and applied new molecular and computational technologies to elucidate chromatin folding patterns at kilobase-resolution genome-wide\, thus discovering that long-range looping interactions in cis and inter-chromosomal interactions in trans change substantially during neural lineage commitment\, somatic cell reprogramming\, activation of post-mitotic neural circuits\, and in neurological disorders. We have demonstrated that cohesin-mediated loops are necessary for the establishment of new gene expression programs in post-mitotic neurons\, including the upregulation of genes encoding axon guidance\, dendritic spine morphology\, and synaptic plasticity during neuron maturation in vivo as well as activity-dependent transcription during neural stimulation in vitro. We have also identified cohesin-mediated loops anchored by divergently-oriented CTCF binding sites that are necessary and sufficient for the firing efficiency and localization of human replication origins during S phase re-entry after mitosis. Using fragile X syndrome as a natural perturbation\, we have uncovered BREACHes (Beacons of Repeat Expansion Anchored by Contacting Heterochromatin) – rare inter-chromosomal interactions connecting heterochromatinized synaptic genes susceptible to repeat instability\, thus providing early insight into the genome’s structure-function relationship. Here\, I will present new unpublished data describing 3D genome miswiring in a human neuron model with rare familial Alzheimer’s mutations as well as the functional link among loops and activity-dependent gene expression during neural circuit activation in vitro and in vivo. The long-term goal of the Cremins lab is to elucidate how the genome’s structure-function relationship influences synaptic plasticity and neurophysiology during memory encoding and consolidation and how this goes awry in intractable neurological disorders. \nBio:\nJennifer Phillips-Cremins\, Ph.D. is an Associate Professor and Deans’ Faculty Fellow in Engineering and Medicine at the University of Pennsylvania with primary appointments in the Departments of Genetics and Bioengineering. Dr. Cremins obtained her Ph.D. in Biomedical Engineering from the Georgia Institute of Technology in the laboratory of Andres Garcia. She conducted a multi-disciplinary postdoc in the laboratories of Job Dekker and Victor Corces. Dr. Cremins runs the Laboratory of Chromatin and Spatial Neurobiology at UPenn. Her primary research interests lie in understanding the long-range chromatin architecture mechanisms that govern neural specification and synaptic plasticity in healthy neurons and how chromatin-synapse communication is dysregulated in neurodevelopmental and neurodegenerative diseases. She has been selected as a 2014 New York Stem Cell Foundation Robertson Investigator\, a 2015 Albert P. Sloan Foundation Fellow\, a 2016 and 2018 Kavli Frontiers of Science Fellow\, 2015 NIH Director’s New Innovator Awardee\, 2020 NSF CAREER Awardee\, a 2020 CZI Neurodegenerative Disease Pairs Awardee\, the 2022 ISSCR Susan B. Lim Outstanding New Investigator Award\, and as a recipient of the 2021 NIH Pioneer Award.
URL:https://rna.umich.edu/events/rna-innovation-seminar-jennifer-e-phillips-cremins-ph-d-associate-professor-and-deans-faculty-fellow-biomedical-engineering-and-human-genetics-penn-epigenetic-institute/
LOCATION:BSRB – Kahn Auditorium
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