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 58 for “"CRISPR/Cas9 gene editing"”.
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Investigating the role of chromatin modifications in CRISPR/Cas9 gene editing
… and heterochromatin have been shown to impede CRISPR/Cas9 editing efficiency. Conversely, Cas9 can open previously inaccessible regions of DNA, and transcriptionally silent targets can usually be edited without difficulty. In order to address this paradox, we have developed a method that …
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Modeling Alzheimer's Disease Using CRISPR/CAS9 Gene Editing and Induced Pluripotent Stem Cells Reveals Conserved Cellular Mechanisms
… autosomal dominant familial AD (fAD) result from genetic mutations in three key genes: amyloid precursor protein (APP), and two APP processing-related genes (presenilin-1 (PSEN1), and presenilin-2 (PSEN2)), supporting the theory that altered APP metabolism is a central cause of AD. However, which …
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Interrogating novel functions of the I kappa B kinases via CRISPR-Cas9 gene editing and small molecule inhibition
… of NF-κB transcription factor activity. Seminal genetic studies in knockout (KO) mouse embryonic fibroblasts (MEFs) have defined two pathways of NF-κB activation; a canonical pathway, activated in response to cytokines such as TNFα/IL-1β, that requires NEMO and predominantly IKKβ catalytic …
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Determining the Roles of the Aldehyde Dehydrogenase Enzymes 5 and 6 during Icewine and Table Wine Fermentation in a Commercial Wine Yeast Using CRISPR-Cas9.
… imbalance during Icewine fermentation with ALD gene expression patterns indicating a role of Ald3p encoded by ALD3 in elevating the acetic acid whereas in table wine, ALD6 expression dominated. In the overall research program from our laboratory, the goal is to remove all five of the ALD genes, …
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Rev7 is a novel regulator of chemotherapeutic response in drug-resistant lung cancer
… response (DDR) mechanisms. In this thesis I used CRISPR-Cas9 gene-editing and other molecular biology and biochemical techniques to examine the functional relevance of that Rev7, a multi-functional translesion synthesis (TLS) DNA damage tolerance protein in drug-resistant cancers.
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DESIGN AND INVESTIGATION OF DUMBBELL-SHAPED DNA MINIMAL VECTORS FOR CRISPR/CAS9 EDITING
… DNA vectors for the delivery of the CRISPR/Cas9 system. Using three targets, i.e. glucose-6-phosphate dehydrogenase (G6PD) Mahidol, G6PD Mediterranean and Southeast Asian Ovalocytosis, and a dual reporter assay, we demonstrated that dumbbell vectors offer a viable alternative to …
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NK Cells and Their Role in Disease and Cancer Treatment
… into tumors. NK cells are involved in the pathogenesis of a number of diseases and in this thesis we will explore NK cells and their role in disease and cancer treatment. First, we will discuss antibody dependent cell mediated cytotoxicity (ADCC) and how deficiencies in ADCC play a role in human …
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UNCOVERING THE EVOLUTION AND DEVELOPMENT OF A NOVEL ABDOMINAL APPENDAGE IN BLACK SCAVENGER FLIES (SEPSIDAE: DIPTERA)
… at least two species. Next, I use an optimized CRISPR/Cas9 gene editing system to test the role of candidate genes in its development in two species with morphologically distinct sternite brushes: Themira biloba and Perochaeta dikowi. I find that doublesex and abdominal-A have been co-opted into …
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Cell Wall Lipids Promoting Host Angiogenesis During Mycobacterial Infection
… an important bacterial determinant of host angiogenesis. We found that PcaA-modified trehalose dimycolate, an abundant glycolipid in the mycobacterial cell wall, drives activation of host VEGF signaling and subsequent granuloma vascularization. To facilitate our continuing investigation of …
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Modulating Immunometabolism to Improve The Activity of Car-Nk Cells Targeting Cd70 In Renal Cell Carcinoma
… (TME). Moreover, the limitations of generating an autologous cell product, such as cost of manufacture, and the challenges of toxicity with CAR-T cells highlight the need to develop new cell therapy products that are at the same time effective and safe.</p> <p>We propose an innovative …
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Convective intracellular macromolecule delivery for cell engineering applications
… cell viability (>95%). Successful experiments in CRISPR-Cas9 gene editing and intracellular gene expression analysis demonstrate potential to overcome the most prohibitive challenges in intracellular delivery for cell engineering.
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Effects of Pharmacological and Genetic Disruption of Chemokine Receptor Cxcr4 In B-Cell Acute Lymphoblastic Leukemia
… an <em>in vitro</em> and <em>in vivo</em> CXCR4 genetic deletion model of B-ALL cells generated using the CRISPR-Cas9 gene editing technology. The CXCR4 Knockout cells display defective chemotaxis and migration beneath BMSCs. Moreover, the BMSCs fail to rescue the CXCR4 Knockout cells from …
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The Role of Arabidopsis thaliana Clade A1 Heat Shock Transcription Factors in Growth and Development
… flowering. A number of candidate developmental genes identified to be regulated by HSFA1b could not be satisfactorily confirmed using the HSFA1 quadruple knockout due to the mutant being a hybrid of 2 accessions (WS-0 and Col-0). Therefore, a new quadruple mutant was generated using the …
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Caspase isoforms in inflammasome activation
… lupus familiaris), for example, has a pseudogene for NLRC4 and has a unique caspase-1/4/11 hybrid gene (CASP1-4/5/11) comprising the caspase-1 caspase recruitment domain (CARD) and the catalytic domain of caspase-4/5/11. Dogs produce bioactive IL-1β despite the apparent lack of the …
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Elucidating the molecular mechanisms of p110δ activation in T cell antigen receptor signalling
… used a combination of proteomic, biochemical and gene editing approaches to identify proteins that are involved in the regulation of p110δ activity during TCR signalling. This work has optimised the AviTag affinity purification system for the isolation of endogenous p110 isoforms from primary …
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Targeting Calpain-1 and Calpain-2 for Prevention of Breast Cancer Metastasis: In Vivo Insights and Drug Discovery Approaches
… potential as therapeutic targets, we used CRISPR-Cas9 gene editing to knock out calpain-1 and/or calpain-2 in MDA-MB-231 triple negative breast cancer (TNBC) cells. Compared to WT cells, calpain knockouts exhibited a 79% reduction in in vitro migratory capacity and an approximately 83.4% …
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ARFGEF mutations: A mechanism for breast-to-brain metastasis
… responsible for driving metastasis, the specific gene alterations that promote brain metastasis remain unknown. Breast-to-brain metastasis occur when primary breast tumour cells disseminate to the brain, proliferating to form secondary tumours. Recent research has shown that metastatic brain …
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Entamoeba histolytica-Induced Caspase-4 Activation Regulates IL-1β Secretion Through Caspase-1
… was independent of ASC and NLRP3. Using CRISPR/Cas9 gene editing of caspase-4 and caspase-1 in human macrophages, we determined that caspase-1 and bioactive IL-1β release was highly dependent on caspase-4 activation in response to Eh. Formaldehyde cross-linking to stabilize …
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The Maturation of Human Pluripotent Stem Cell-Derived Retinal Ganglion Cells and Their Degeneration in Glaucoma
… eye and the brain is severed leading to the degeneration of retinal ganglion cells (RGCs) and eventual blindness. A need exists to better understand the maturation of human RGCs as well as their degeneration, with the goal of developing new therapeutics diseases like glaucoma. Human pluripotent …
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Cross-Species Evolution of New AAV Variants
<p>Therapeutic gene transfer and genome editing require effective delivery of genetic cargo to target cells and tissues. Recombinant adeno-associated viral (AAV) vectors are a promising delivery platform, but ongoing clinical trials continue to highlight a relatively narrow therapeutic window. …
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