Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 20 of 33 for “"CRISPR screen"”.
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Characterization of the Antiviral Effector IFI6
… response to flavivirus infection, a genome-wide CRISPR screen was carried out. Two of the top hits from the screen were IFI6, a previously identified ISG long predicted to be antiviral, and BiP, a luminal chaperone in the endoplasmic reticulum (ER). I questioned whether IFI6 was important for the …
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Identifying Epigenetic Regulators Of Tumor Dormancy And Recurrence
… mouse model of breast cancer, we performed a CRISPR screen to identify novel epigenetic regulators of tumor dormancy and recurrence. We identified HDAC10 and KMT2E as recurrencepromoting genes; tumor cells with Hdac10 or Kmt2e loss were depleted during dormancy and their loss delayed …
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Biases and Blind-Spots In Genome-Wide Crispr-Cas9 Knockout Screens
<p>Adaptation of the bacterial CRISPR-Cas9 system to mammalian cells revolutionized the field of functional genomics, enabling genome-scale genetic perturbations to study essential genes, whose loss of function results in a severe fitness defect. There are two types of essential genes in a cell. …
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The PNUTS-PP1 Complex Acts as an Intrinsic Barrier to Kaposi's Sarcoma Associated Herpesvirus Gene Expression and Replication
… of a KSHV reporter gene in a genome-wide CRISPR screen. PNUTS depletion enhances global KSHV gene expression and overall viral replication. Mechanistically, PNUTS requires PP1 interaction, binds viral RNAs downstream of polyadenylation sites, and restricts transcription readthrough of …
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Loss of Ptdss1 in tumor cells improves anti-PD-1 therapy
… immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to …
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Utilizing the IN4MER CRISPR/CAS12A Multiplex Knockout Platform To Investigate Synthetic Lethality in the Human Genome
… to support genome- wide and genetic interaction screening; 3) observations and analyses to account for varied guide efficiency in multiplex CRISPR screen data.</p> <p>Given the approximated 20,000 protein-coding genes in the human genome, the search space for synthetic lethal genes is too vast to …
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Revealing the role of Gα13 in germinal centre lymphomas
… in primary, human germinal centre (GC) B cells. CRISPR knock-out of *GNA13* in primary GC B cells provides a remarkable fitness advantage. Indeed, in a focused and genome-wide CRISPR screen the Gα13 pathway was among the top-hit pathways, revealing its potent tumour suppressor activity in human …
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The Heme-Regulated Inhibitor Pathway Modulates Susceptibility of Poor Prognosis B-Lineage Acute Leukemia to BH3-Mimetics
… explore how DHA represses MCL-1, a genome-wide CRISPR screen identified that loss of genes in the heme synthesis pathway renders mouse BCR-ABL+ B-ALL cells resistant to DHA-induced death. Mechanistically, DHA disrupts the interaction between heme and the eIF2α kinase heme regulated inhibitor …
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Identification and characterisation of Pu.1-driven gene regulatory complexes and networks in Acute Myeloid Leukaemia.
… by the DepMap consortium across genome-wide CRISPR screen. This suggests a fundamental role for Pu.1 in leukaemia maintenance and our study aims to provide mechanistic detail to this observation. Throughout this study, we utilise proteomic, transcriptomic, genomic and functional approaches …
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DNA Damage Response in Huntington’s Disease and Naked Mole Rat Brain Ageing
… and impairments in specific DNA repair pathways. CRISPR screens identified novel genes and pathways that modulate the cellular response to DNA damage in the context of expanded HTT. This thesis also investigated other DDR genes involved with repeat expansion in HD and identified potential …
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Targeting the B-Cell Receptor in Diffuse Large B-Cell Lymphoma
… studied regulators of the BCR using whole genome CRISPR screens. First, I created an assay for internalisation of the BCR and combined it with a sorted CRISPR screen to try to understand how the BCR transits to intracellular signalling platforms. Next, I used the anti-CD79B antibody drug conjugate …
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DNA repair deficiencies as a biomarker for treatment response in acute myeloid leukaemia
… efficiency of the in vitro models. A pooled CRISPR screen and single cell sequencing ascertained which mutations may be driving the DDRD phenotype in patients. Kaplan Meier analysis showed the DDRD positive patienst survived significantly worse than the DDRD negative cohort. Whole exome …
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Investigation of conventional and unconventional protein secretion using galectin-3
… to assess protein secretion using a genome-wide CRISPR screen. As galectin 3 binds to cell surface glycoproteins, galectin-3 on the cell surface was used to assess secretion of these glycoproteins. Hits were validated by a glycoprotein secretion assay. Using this pipeline, 93 hits were identified …
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Translational regulation in aggressive B-cell lymphomas
… non-coding regions, and design a knock-down CRISPR screen library to identify those important for B-cell survival.
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Identifying regulators of cytotoxic T cell function through molecular and genetic screening
… In this study, I aimed to establish the CRISPR-Cas9 gene editing technology in primary T cells and to optimise screening approaches to identify regulators of CTL killing. The first half of the thesis focuses on primary mouse CTL. The CRISPR technology was successfully optimised in CTL …
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Ubiquitin E3 ligase mediated regulation of HMG-CoA Reductase
Loss-of-function genetic screens are a powerful approach to identify the genes involved in biological processes. For nearly a century, forward genetic screens in model organisms have provided enormous insight into many cellular processes. However, the difficulty in generating and recovering …
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Targeting Vasculogenic Mimicry in Cancer
… and leveraged this to conduct a genome-wide CRISPR screen using a bespoke dual gRNA-tRNA expression system. Through these approaches, we identified a shortlist of candidate genes to functionally investigate for VM capabilities to validate already known and uncover previously unknown …
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Understanding the Cancer Resistance Mechanisms of the Naked Mole-Rat
… publication of the NMR genome and advances in CRISPR-Cas9 gene editing, I set out to systematically interrogate the NMR genome through a genome-wide CRISPR screen to identify the genes responsible for its cancer resistance. My approach was based on Tian et al.’s finding that the NMR cells are …
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The Benefits and Detriments of Aneuploidy in Cancer
… cells can relieve their proliferation deficit. A CRISPR screen for improved growth of trisomy 21 cells identified several genes of interest that may specifically contribute to proliferation of trisomy 21 cells. Ultimately, more work is needed to understand how these genes of interest interact with …
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Mapping the transcriptional landscape of haematopoietic stem and progenitor cells
… further used to identify candidate genes for a CRISPR screen investigating genes implicated in HSC biology. These candidate gene perturbations were interrogated for changes in the expression of the HSC marker EPCR, as well as changes in apoptosis and lineage output. Transcription factors play a …
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