The RNA Transcript, December 13, 2021 |
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CRISPR to KLIPP Cancer
While most efforts involving CRISPR are focused on genome editing, the CRISPR machinery could also be used as a molecular weapon to slice up chromosomes of cancer cells. Research has shown that chromosomes may undergo a “catastrophic” event early in the process of carcinogenesis causing multiple breakages. While many cells die in such events, some of them repair the damaged chromosomes in ways that give them the power to multiply faster and to form tumors. Such chromosome rearrangements bring into close proximity pieces of chromosomes that are normally far apart. The formation of chromosome rearrangements is unique to cancer cells and is observed across all forms of cancer.
“This is a cancer's Achilles’ heel, right there,” said Mats Ljungman, Professor of Radiation Oncology and co-director of the Center for RNA Biomedicine, “and we could use CRISPR to specifically target these chromosome rearrangement junctions and cut tumor DNA strands similarly to what is done with radiation therapy, but without affecting normal cells."
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Photo: KLIPP team, Summer 2021. From left to right: Mats Ljungman, Radhika Suhas Hulbatte, Huibin Yang, Lauren Hertzer, and Natalie Gratsch. Photo: Elisabeth Paymal |
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18 U-M scientists and scholars present their research on three RNA therapeutics areas: mRNA vaccines, ASOs, and CRISPR. The second half of the magazine highlights the main activities of the Center for the July 2020–June 2021 period.
Special thanks to all our contributors!
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Monday, December 13, 2:00 pm ET, Zoom | University of Michigan, Chemical Biology, Dissertation Defense
"Understanding the Mechanism of Disaggregation and Unfolding of the hsp100 Family Through cryo-EM Structure Determination"
Alexandrea Rizo, Doctorate Candidate
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Tuesday, December 14, 12:30 pm ET, Chem 1706 and Zoom | University of Michigan, Chemistry, Dissertation Defense
"Devising a Rapid Single Molecule FRET Biosensing Assay for Nucleic Acid Detection"
Kunal Khanna, Doctorate Candidate
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Tuesday, December 14, 3:00 pm ET, Zoom | University of Michigan, Chemical Engineering, Dissertation Defense
"Scalable Networks of Engineered Extracellular Matrix as Biomimetic Tissue Culture Models with Defined Heterogeneity"
Dylan Neale, Doctorate Candidate
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"A RNA-guided approach to epigenetic therapy"
“Efficient integration of spatial transcriptomics and single cell sequencing technologies for in depth tissue interrogation”
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Thursday, December 16, 12:00 pm ET, Zoom | University of Michigan, Chemical Engineering, Dissertation Defense
"Engineering Multifunctional Nanoparticles: Applied Nanoscale Therapeutics"
Jason Gregory, Doctorate Candidate
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Thursday, December 16, 2:00 pm ET, Zoom | University of Michigan, Chemical Biology, Dissertation Defense
"Structural and Biochemical Mechanisms of MLL1 Activation on Chromatin"
Alex Ayoub, Doctorate Candidate
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Thursday, December 16, 5:00 pm ET, Zoom | University of Michigan, Taubman Institute
"See Everything Quickly through SEQ-Scope — Microscopic Examination of Spatial Transcriptome"
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Monday, December 20, 4:00-5:00 pm ET, Zoom, and BSRB,
ABC seminar rooms | University of Michigan Center for RNA Biomedicine, RNA Faculty Candidate Seminar
Co-hosted with the Department of Biological Chemistry, and the Program in Biophysics
“Modulation of the MALT1 pre-mRNA structure by hnRNP proteins regulates T cell activation”
Institute of Structural Biology, Helmholtz Zentrum Munich, Germany
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February 17–18, 2022 | University of Michigan, Chemistry-Biology Interface Program Symposium
Abstract Submission: December 10, 2021–January 10th, 2022
The symposium will feature a range of faculty and graduate student speakers and poster sessions focusing on research at the interface of chemistry and biology. The symposium offers a forum for trainees around the University to present their original research and engage in stimulating scientific discussion.
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For press releases and blog articles about your upcoming top journal publications, please
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Our members' publications are available through Altmetric. Sept queries are currently available: CRISPR, microRNA, molecule, RNA, RNA therapeutics, transcriptome, and translation. Please make sure to have at least one of these keywords in your title. Below are recent highlights.
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Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures
M. Zafferani, C. Haddad , Le Luo , J. Davila-Calderon, Liang-Yuan Chiu, C. Shema Mugisha, A. Monaghanan, D. Kennedy, J. Yesselman, R. Gifford, A. Tai, S. Kutluay, Mei-Ling Li, G. Brewer, B. Tolbert and A. E. Hargrove, Science Advances, 26 Nov 2021, Vol 7, Issue 48, DOI: 10.1126/sciadv.abl6096
Abstract: ... Here, we report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication through targeting of conserved structured elements within the viral 5′-end. Nuclear magnetic resonance–based structural studies revealed specific amiloride interactions with stem loops containing bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Amilorides represent the first antiviral small molecules that target RNA structures within the 5′ untranslated regions and proximal region of the CoV genomes. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA–targeted antivirals.
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TissueNexus: a database of human tissue functional gene networks built with a large compendium of curated RNA-seq data
Abstract: Mapping gene interactions within tissues/cell types plays a crucial role in understanding the genetic basis of human physiology and disease. Tissue functional gene networks (FGNs) are essential models for mapping complex gene interactions. We present TissueNexus, a database of 49 human tissue/cell line FGNs constructed by integrating heterogeneous genomic data. ...
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