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DTSTART;TZID=America/Los_Angeles:20260921T113000
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DTSTAMP:20260914T191617Z
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SUMMARY:Headrick\, C. (BMEB) - The Regulation of mRNA Cleavage in Nonsense-mediated mRNA Decay: From Inside (intra-pathway determinants) Out (extra-pathway regulation)
DESCRIPTION:Nonsense-mediated mRNA decay (NMD) is a translation-coupled quality control pathway that degrades mRNAs that harbor a premature termination codon (PTC) and 5-30% of normal cellular mRNAs. The NMD field sits at a pivotal moment with recent developments that endonucleolytic cleavage is the primary mechanism of mRNA decay conserved across metazoans. Discovery of a conserved NMD cleavage mechanism sets the stage for a dissection of mRNA cleavage determinants and regulators. \nTo better understand how mRNA cleavage during NMD is regulated\, I will use degradome-seq based approaches via 5’RACE-seq (Rapid Amplification of 5’ cDNA Ends) to isolate the cleavage products of the NMD pathway. I will first focus my analysis on core NMD factors and helicase UPF1\, the binding site of NMD decay effectors\, to examine how UPF1 enzymatic activity affects mRNA cleavage transcriptome-wide (Aim 1). In parallel\, to assess extra-pathway regulation of mRNA cleavage during NMD\, I will identify endogenous negative regulators of mRNA cleavage (Aim 2). Contemporary models of NMD are deprived of the functional impact of cellular NMD inhibitors. I will access this novel functional space with an innovative application of CRISPR screening and quantitative\, high-throughput NGS\, known as ReLiC (RNA-linked CRISPR) paired with degradome analysis. \n  \nEvent Host: Camille Headrick\, Ph.D. Student\, Biomolecular Engineering & Bioinformatics  \nAdvisor: Joshua Arribere \n 
URL:https://events.ucsc.edu/event/headrick-c-bmeb-the-regulation-of-mrna-cleavage-in-nonsense-mediated-mrna-decay-from-inside-intra-pathway-determinants-out-extra-pathway-regulation/
LOCATION:Biomedical Sciences Building\, 575 McLaughlin Drive
CATEGORIES:Ph.D. Presentations
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DTSTART;TZID=America/Los_Angeles:20260925T130000
DTEND;TZID=America/Los_Angeles:20260925T150000
DTSTAMP:20260911T151906Z
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SUMMARY:Mastoras\, M. (BMEB) - Polishing genome assemblies and leveraging their improved quality to study centromere variation
DESCRIPTION:A complete and accurate genome reconstruction serves as the foundation for studying an organism’s biology and the mechanisms underlying disease. It is particularly critical for reference genomes\, which provide a universal coordinate system for downstream genomic analysis. Errors or missing sequences in a reference genome create bias in all of the studies built on top of them. The Human Pangenome Reference Consortium (HPRC) seeks to address this bias by transitioning the field to a pangenome reference\, a graph based collection of many genome assemblies\, providing a better representation of variation in the human population. Removing errors in the HPRC assemblies is critical to ensure the pangenome serves as a robust standard for genomic variant discovery. In the first part of my thesis\, I improve the base level accuracy of the HPRC release 2 assemblies (HPRC2) with a machine learning model for assembly polishing called DeepPolisher. Next\, I make additional contributions to reference-based genomic analysis by polishing reference genomes of other model organisms\, and helping to develop a new method for de-novo assembly and variant calling from a single-flow cell nanopore sequencing protocol. Finally\, I take advantage of the highly accurate\, near complete assemblies from HPRC2 that I improved with DeepPolisher to study a region only recently made accessible to genomics analysis: the human centromere. I apply the tool Centrolign\, the first ever multiple-sequence-aligner for centromeres to the HPRC2 assemblies\, establishing precise estimates of mutation rates and spatial variation patterns across centromeric arrays. \nEvent Host: Mira Mastoras\, Ph.D. Candidate\, Biomolecular Engineering & Bioinformatics \nAdvisor: Benedict Paten \nZoom: https://ucsc.zoom.us/j/98960011053?pwd=mFKCwtSIhvT5FvEURbE85lRbbMvzuo.1 \nPasscode: 118488
URL:https://events.ucsc.edu/event/mastoras-m-bmeb-polishing-genome-assemblies-and-leveraging-their-improved-quality-to-study-centromere-variation/
LOCATION:Physical Sciences Building\, Physical Sciences Building\, Santa Cruz\, CA\, 95064
CATEGORIES:Ph.D. Presentations
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