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.
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Showing 1 to 20 of 22 for “"CRISPR screens"”.
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Multi-species genome-wide CRISPR screens identify conserved suppressors of cold-induced cell death
… In this thesis, we conduct two genome-wide CRISPR-Cas9 screens in both a cold-sensitive (K562) and cold-resistant (BHK-21) cell line, and uncover GPX4 and related selenocysteine incorporation genes as important for protection against cold-induced cell death. Using genetic knockdowns, along …
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Genome-wide CRISPR Screens to Uncover Novel Therapeutic Targets in Wnt-β-catenin Driven Gastrointestinal Cancers
… therapeutics currently exist that target it. CRISPR/Cas9 gene editing technology has recently allowed for genome-wide loss- of-function screens in vertebrate cells and may therefore be used to identify novel genetic vulnerabilities in human cancer cells. Genome-wide CRISPR screens were …
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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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Experimental Design of Single Cell Sequencing Experiments
… is particularly useful in functional genomics screens that introduce perturbations to investigate and reconstruct the regulatory networks within and between cells. CRISPR screens are the leading method of conducting functional genomics screens due to their specificity, precision and ease of …
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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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Dissecting Host-Viral Interactons Through Focused or Unbiased High-Throughput Genetic Approaches
… and loss of function studies, genome-scale CRISPR screens, and focused CRISPR screens—to gain mechanistic insight of host-viral interactions, focusing on the human immunodeficiency virus type 1 (HIV-1) and the human coronaviruses (HCoVs). I begin this thesis by providing an overview of the …
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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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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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In Situ Perturb-Seq of Transcriptomes and RNA Neural Recordings
… of in situ sequencing, neural recording, and CRISPR screens. An intracellular technology is outlined for encoding neural activity in the form of RNA, theoretically enabling single-cell resolution recording of whole-brain activity. This neural recording system can be coupled with perturb-seq in …
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TUMOR-PROMOTING FUNCTION AND MOLECULAR REGULATION OF TSPAN8 IN LIVER CANCER
… in the DEN-induced liver cancer model. Using CRISPR/Cas9 knockout approach, we demonstrated the critical role of TSPAN8 in the invasion and anchorage-independent colony formation of liver cancer cells. Moreover, orthotopic implantation of mouse liver cancer cells into synergetic recipient mice …
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Genomewide Crispr/Cas9 Screen Identifies Network of Protein Complexes That Regulate Trim24
… this possibility, I performed a genomewide CRISPR/Cas9 screen library using fluorescence activated cell sorting (FACS) to identify regulators of TRIM24. The screen was enabled by two innovations. I engineered cells with an in-frame knock-in of mClover3 to the endogenous copy of TRIM24 to …
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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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Decoding CD4+ T cell activation by multi-modal phenotyping
… first chapter, I optimise a protocol for pooled CRISPR-KO screens in primary CD4+ T cells with single-cell RNA sequencing as a read-out, and implement it to explore the role of 20 immune-disease genes on T cell activation. The results of this chapter will be instrumental for the design of larger …
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Histone Lysine Demethylase KDM4A as a Therapeutic Target for Small Cell Lung Cancer
… analyzing publicly available data from shRNA and CRISPR screens in addition to our own RNA-seq expression data, I identified KDM4A as a potential candidate to target in SCLC. To underscore the potential of KDM4A as an anti-SCLC target, I tested the response phenotypes of etoposide and three JmjC …
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Exploiting Chemogenetic and Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities
<p>The advent of CRISPR technology and its adaptation to the mammalian genome made whole-genome knockout screens possible directly in human cells. Gene knockout answers how essential that gene is for cell fitness and proliferation. Genes showing moderate to severe fitness defects are called …
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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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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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Investigation of Trans-factors responsible for the developmentally linked instability of a highly regulated mRNA in Trypanosoma brucei
… Cas9 was performed in *T. brucei* and the CRISPR system was assessed for future forward genetic screens, the results of which were highly encouraging. The first method assessed involved single target knockout by targeted Cas-9 action which proved sufficiently effective to suggest feasible …
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