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 21 for “"CRISPR Screening"”.
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UNRAVELING TAZ REGULATION IN BREAST CANCER BY CRISPR SCREENING
… we conducted a series of loss-of-function CRISPR/Cas9 pooled genetic screens in vitro and in vivo on a selected subset of genes, previously identified in our laboratory as modulators of TAZ transcriptional activity. With this study we aimed to identify genes crucial for breast cancer cells …
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Identifying regulators of natural killer cell development through CRISPR screening of common lymphoid progenitors
… using the mouse as a model organism. Pooled CRISPR screens were performed by culturing CRISPR-edited primary common lymphoid progenitors in vitro to generate NK cells and ILC2s, so that the regulators unique to each lineage could be discovered. Reassuringly, this approach identified …
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Determining therapeutically actionable genetic interactions in human cancer at scale using multiplexed CRISPR screening
… a high-throughput multiplexed combinatorial CRISPR/Cas9 pooled screening approach to systematically identify SL interactions. A novel tRNA-based dual guide expression system was used to construct the Synergy library, enabling comprehensive and unbiased monogenic and digenic perturbation of …
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A SEARCH FOR EPIGENETIC VULNERABILITIES OF AML CELLS PERFORMED BY A CDK INHIBITOR¿BASED CRISPR SCREENING
… epigenetic therapies. The present study employed CRISPR-Cas9 dropout screenings to systematically identify chromatin-related vulnerabilities emerging upon cell cycle manipulation. Using a Cas9-expressing AML cell line, we screened more than 600 epigenetic regulators in the context of CDK …
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Genome-wide CRISPR Screening in FBXW7-mutant Cells Uncovers Multiple Druggable Synthetic Lethal Interactions Involving Cell Cycle Control
Current standard of care chemotherapeutics broadly target actively dividing cells, with both healthy and cancerous cells being damaged, causing toxic side effects. Personalized oncology aims to selectively target cancerous cells based on their mutational status, minimizing toxic and life-altering …
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Image-based pooled genetic screens for complex cellular phenotypes
… functional genomics approaches such as pooled CRISPR screening, the cellular phenotypes that can be linked to gene function in a pooled screen have been restricted to measurement by sequencing, and are often a step removed from the biological process of interest. In contrast, microscopy …
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Genome scale identification of HIV Dependency factors across multiple HIV-1 strains
In this thesis, I developed a method called HIV-CRISPR screening at genome-wide scale, and then at a smaller, targeted scale, to uncover novel genes that may act as HIV-1 dependency factors. By using a screening technique which assesses enrichment or depletion of guide based on HIV-1 release from …
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The Effects of Chromatin Remodeling and Pseudokinase Activity on Liver Pathophysiology
… Finally, we harness the power of in vivo CRISPR screening within the liver to identify the pseudokinase STK31 as a positive regulator of hepatocyte proliferation and liver oncogenesis. Our findings underscore the important role that chromatin remodeling has in enforcing hepatocyte identity …
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Targeting Telomerase Overexpression by Synthetic Dosage Lethality
… We used a combination of pooled shRNA and CRISPR screening platforms to comprehensively query the entire human genome and identify hTERT-specific Synthetic dosage lethality (SDL) interactions. Our screens identified several potential SDL genes specific to hTERT in the model cell lines. We …
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Identification of novel genetic vulnerabilities and therapeutic targets in acute myeloid leukaemia using CRISPR dropout screens
… regularly interspaced short palindromic repeats (CRISPR) screening platform and use it to identify genetic vulnerabilities in AML cells. This work led to the identification of 492 AML-specific cell-essential genes, including several established therapeutic targets such as that represent new …
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Computational and experimental methods for CRISPR-based saturation mutagenesis screens
… of the human genome. The emergence of CRISPR technology has enabled the efficient and diverse installation of genetic variation in situ, leading to its widespread use in functional genomics. The application of high-throughput CRISPR saturation mutagenesis screens for the functional …
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LINKING TRANSCRIPTIONAL AND MORPHOLOGICAL HETEROGENEITY TO THERAPEUTIC VULNERABILITIES IN GLIOBLASTOMA
… profiles” from genome-wide recessive pooled CRISPR-Cas9 screens. Furthermore I have contributed methods and analyses for benchmarking state-of-the-art computational methods aiming at preprocessing CRISPR screening data, and correcting technology-specific biases, such as the tendency of the …
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Finding the Best Gene Candidate(s) as a Potential Therapeutic Target for N-MYC Overexpressing Neuroendocrine Prostate Cancer (NEPC)
… Vizeacoumar lab performed genome-wide shRNA and CRISPR screening to identify genes that become essential in N-MYC overexpressing cells. My work will specifically focus on validating three candidate genes (WNT1, SOX17, and FOXN1) identified from the genome-wide screen. Moreover, to suggest a more …
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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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IDENTIFICATION OF FACTORS INVOLVED IN DOUBLE STRANDED RNA-INDUCED CELL DEATH THROUGH GENOME-WIDE CRISPR SCREENS
… regularly interspaced short palindromic repeats (CRISPR) screening and integrative analysis to prioritize gene targets that favour/inhibit dsRNA-dependent cell death. The screen revealed that RNA surveillance, RNA Polymerase II Transcription Initiation, Mitochondrial translation and respiratory …
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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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Investigating upstream regulators of FOXA1 in breast cancer
… FOXA1 protein stability, we coupled whole-genome CRISPR screening with a reporter system expressing a FOXA1-fluorophore fusion. Using this approach, we identified a mild FOXA1 stabiliser – PIGS, a poorly characterised protein involved in GPI anchor biosynthesis in the endoplasmic reticulum. In …
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Deciphering Cancer Metabolic Dependencies in the Tumor Microenvironment
… tumor contexts. This work employs unbiased CRISPR-guided genetic screens and large-scale metabolomics analyses to identify the metabolic dependencies of cancer cells under lipid saturation stress and characterize the in vivo specific metabolic liabilities of pancreatic tumors. Cells require …
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CRISPR AS A TOOL FOR TARGET DISCOVERY AND TECHNOLOGICAL INNOVATION: HIGH-THROUGHPUT CBE SCREENING TO EVALUATE M6A MODIFICATION PATHWAY IN CANCER PROLIFERATION AND DRUG RESISTANCE, AND INNOVATIVE PRIME EDITING STRATEGIES FOR DISEASE MODELLING AND THERAPY
… Regularly Interspaced Short Palindromic Repeats (CRISPR) Cytosine base editing (CBE) screening to perform saturating mutagenesis of m6A-pathway effectors. In details, we assessed the effect of single nucleotide variants (SNVs) in CRC proliferation, highlighting domains of m6A effectors that are …
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