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 75 for “"genetic screens"”.
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Image-based pooled genetic screens for complex cellular phenotypes
… the entire organism. However, knowledge of the genetic and molecular basis for many cellular phenomena is incomplete, limiting the ability to reverse disease states and engineer biological function. Although recent technologies have enabled scalable functional genomics approaches such as pooled …
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Genetic screens in vivo using the CRISPR/Cas9 system
… vulnerabilities in vivo adopting methods used in genetic screens. By harnessing the information obtained from large datasets in vitro and the utility of cutting-edge endogenous mouse models, the general aim of this work is to create a method that shortens the gap between findings in the lab to …
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Molecular analysis of insulin action using high throughput genetic screens
The insulin-stimulated uptake of glucose by muscle and adipose is vital for the maintenance of glucose homeostasis in the body. This uptake primarily occurs through the action of the insulin-regulatable glucose transporter GLUT4, which is rapidly translocated to the plasma membrane in response to …
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Pectin: New insights from an old polymer through pectinase-based genetic screens
… obtained by a recently developed pectinase-based genetic screen. Arabidopsis thaliana seedlings grown in liquid medium containing pectinase solutions exhibited particular phenotypes: they were dwarfed and slightly chlorotic. However, when genetically different A. thaliana seed populations (random …
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Applications of forward genetic screens to LncRNAs, cancer immunotherapy, and cellular engineering
Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. By perturbing thousands of genes simultaneously and selecting for a desired phenotype, genetic features can be systematically …
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Identification of components required for mitophagy and mitochondrial inheritance by genetic screens in yeast
… the autophagic membrane. In the second part, a genetic screen revealed that mitochondrial dynamics is important for the inheritance of mitochondria into the daughter cell. In yeast, mitochondria are transported along the actin cytoskeleton by the myosin V motor protein Myo2. The mutant myo2(LQ) …
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Genetic screens of RNA binding proteins identify a role for N6-methyladenosine in promoting B cell differentiation
… unexplored. My project utilised high-throughput genetic screens to identify roles for RBPs in lymphocytes. Initially, I generated custom sgRNA libraries targeting RBPs to facilitate CRISPR/Cas9 mediated gene knockout screens in either human or mouse contexts. Then, I employed these reagents to …
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Functional Genomic Studies of Cancer Immune Evasion Using In Vitro and In Vivo CRISPR/Cas9 Genetic Screens
… technologies. The advent of CRISPR/Cas9 genetic screens has revolutionised our ability to interrogate the cancer genome and identify its genetic vulnerabilities. With these in mind, I have carried out pooled in vitro and in vivo CRISPR/Cas9 genome-wide genetic screens, in order to …
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A streamlined Workflow for Transposon Mutagenesis in Corynebacterium glutamicum Based on Third-Generation Sequencing and its Application for Advanced Genetic Screens
… Technologies (ONT) nanopore Sequencing. Mobile genetic elements (MGEs) destabilize the genetic material of their hosts. While this can contribute to evolutionary plasticity in nature, it is often detrimental in a research and industrial context. Therefore, this work presents and builds upon the …
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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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A proteomic approach for studying LTR retrotransposon host factors in saccharomyces cerevisae
… that resemble retroviruses, both in their genetic structures and replication cycles. Ty retrotransposition begins in the nucleus with the transcription of Ty RNA. Following translation of Ty proteins, virus-like particles (VLPs) assemble in the cytoplasm. VLPs contain Ty RNA and enzymes …
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Single-cell morphological data reveals signaling network architecture
… from highthroughput morphological data from genetic screens. Our contributions fall into three major categories. 1) To define and apply robust statistical measures to identify genes regulating morphological variability. We develop and thoroughly test methods for measuring morphological …
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Focused CRISPR-Cas9 screens investigating the DNA damage response
… syndromes to developmental disorders. Genetic screens can be used to gain insights into the function of known DDR proteins, identify novel DDR components and highlight potential therapeutic opportunities. We demonstrate that CRISPR-Cas9 gene editing is a useful tool in genetic screens …
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Haploid reporter screens aimed at identification of NF-kappaB regulators
… new members in a pathway is the forward genetic screen. Human haploid genetic screens represent a recent advance in this approach. I have attempted to expand the utility of human haploid genetic screens through the use of transcriptional reporters and developed human haploid reporter …
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Dissecting the Roles of Cancer Cell Lipid Metabolism in Tumor Progression and Immune Evasion
… and implemented loss of function CRISPR-Cas9 genetic screens to identify lipid metabolic dependencies in cancer cells growing under lipid peroxidation or immune pressure. Cancer cells rewire their metabolism and rely on endogenous antioxidants to mitigate lethal oxidative damage to lipids. …
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Sex And Heterochromatin: An Investigation Of Sexual Dimorphism In Drosophila Melanogaster
… not thought to be sexually dimorphic. The genetic basis for the regulation of sex-specific heterochromatin was completely unknown. </p> <p>To determine if roX RNAs localize directly at the heterochromatic regions that they regulate, I generated an MS2-tagged roX1 allele (roX1MS2-6) using a …
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The Role of Compartmentalized Metabolism in Cellular Metal Homeostasis
… of this work, I focused on lysosomes. Unbiased genetic screens performed on cells grown at sub-lethal levels of lysosomal pH inhibition identified several important metabolic pathways in this context. These included central carbon metabolism, cholesterol synthesis and iron homeostasis. While, …
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Identification and characterisation of novel zebrafish brain development mutants obtained by large-scale forward mutagenesis screening
… purpose. In this thesis, I report on two forward genetic screens performed to find new mutants affecting brain development, in particular mutants defective in development and function of the midbrain-hindbrain boundary (MHB), an organiser region that patterns the adjacent brain regions of the …
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High-throughput vertebrate total analysis/screening platform
… high-content high-throughput pharmaceutical and genetic screens on whole zebrafish larvae, and therefore, are well-modularized for adapting different situations. Furthermore, to demonstrate the capability of V-TAS, a screen of lipidoid library for biologics delivery on thousands of animals was …
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Investigating WDR12 as a Therapeutic Target in Breast Cancer
… of improved therapeutics. Data mining through genetic screens suggests that the ribosome biogenesis protein WDR12 is essential for breast cancer cell proliferation. In this study, we characterize the effects of WDR12 knockdown in a panel of breast cancer cells. We show that WDR12 knockdown …
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