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 21 for “"Mutant clones"”.
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The Contribution of Environmental Cues to Early Squamous Tumour Formation in the Upper Gastrointestinal Tract
… tissue types harbour substantial populations of mutant clones similar to those found in cancer. This implies that the accumulation of somatic mutations alone may not be the sole cause of cancer and that other factors are required. Tumours are polyclonal in nature with the interplay between …
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The role of Decapentaplegic (Dpp) in Drosophila wing development
… of loss-of-function and gain-of-function. Mutant clones lacking Dpp signal transduction by knock down Dpp receptor Thick veins (Tkv) do not survive in wing blade due to JNK dependent apoptosis. To get larger mutant clones for analysis, JNK pathway was inhibited by knock down bsk (encodes …
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Accumulation of Somatic Mutations in Normal Human Colonic Epithelium
… of intra-gland competition of stem cell derived clones, a disadvantage is observed for the histone modifier HDAC6, while at the other end of the spectrum, loss of the cohesin member STAG2 strongly advantages affected stem cells. Subsequent clonal expansion beyond the boundary of a single crypt is …
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Fgf4 and Wnt5a/Pcp Signaling Promote Limb Outgrowth by Polarizing Limb Mesenchyme
… is directing cell polarization, then FGF mutant clones will not migrate toward the AER. Therefore, it is expected that these mutant clones would be unable to undergo directed cell movement and/or cell divisions. Early clonal analysis indicates that a response to FGFs appears to be …
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Cell Polarity Regulates Organ Growth Through The Hippo Pathway
… can lead to uncontrolled tissue growth. Cells mutant for the basolateral determinant <em>scribble </em>overproliferate and can form neoplastic tumors. Interestingly, <em>scribble </em>mutant clones that arise in wild-type tissues are eliminated and therefore do not manifest their tumorigenic …
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Characterization of psb O mutants from cyanobacterium synechococcus PCC 7942 and expression of the wild-type gene in escherichia coli
… were: 1) to analyze previously constructed MSP mutants and 2) to subclone, express, and purify the wild-type MSP in Escherichia coli in order to investigate the relationship between structure and function of this protein.Growth rates were compared between bacterial cells harboring only the …
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The natural history of clonal haematopoiesis
… progression. Results By tracking 697 CH clones from 385 individuals aged 55 or older over a median of 13 years, we found that 92.4% of clones expanded at a stable exponential rate in old age, with different mutations driving substantially different growth rates, ranging from 5% (DNMT3A, …
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The Efficacy of Immunotherapy in Preventing Liver Cancer and the Role of Metabolic Zonation in Its Development
… in Ctnnb1 and to delete Arid2. We found that mutant clones arising from zone 1 gradually expanded and persisted, while mutant clones arising from Zone 3 rapidly disappeared over time. However, more tumors ultimately developed in the zone 3 livers than in the zone 1 livers, suggesting that …
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Selection and competition of somatic mutations in normal epithelia
… genes. This thesis explores the behaviour of mutant clones in normal epithelium and how this affects cancer development. The nature of mutant clonal growth and competition in normal epidermis has been a subject of debate. A study found that mutant clone sizes inferred from DNA sequencing of …
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Affinity Maturation of the D1.3 Antibody Using Yeast Surface Display and Flow Cytometry
… indicating excellent differentiation between clones of only slightly different affinity. Optimal equilibrium affinity screening of a randomly mutated D1.3 library was performed with and without an osmotic stressor present in the binding reactions. Osmotic stress yielded a more diverse set of …
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Extracellular matrix protein receptors in Drosophila melanogaster
… of a multi-protein complex. In this work, the mutant phenotype of CD98hc is larval lethal and not temperature sensitive. Clonal analyses of CD98hc mutants show no phenotype of mutant clones in the eye. Genetic interactions in adult tissues or interactions affecting larval lethality between …
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The mutational landscape of normal urothelium
… of our tissues are converted into a patchwork of mutant clones, despite retaining their histologically normal appearance. These clonal expansions are commonly driven by mutations in known oncogenes and tumour suppressor genes, with the driver landscape in a given tissue resembling its associated …
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Study of mutation, mutants, and repair in the blue-green alga Agmenellum quadruplicatum
… but in only a few of these cases were stable mutant clones isolated from the wild type (3, 24). Once it is known that an agent is mutagenic, it becomes useful to study the way in which it affects a cell. For instance, what are the optimum conditions for survival and mutagenesis? Can the lethal …
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The role of space in homeostasis and preneoplasia in stratified squamous epithelia
… tissue. The studied dynamics of Notch and p53 mutant clones in mouse epithelia has been found to be highly distinct, with the former fully colonizing the tissue whereas the latter only partially. I demonstrated that the two mutants’ tissue takeover dynamics can be recapitulated by two distinct …
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Trees and Forests: Data Science and Machine Learning Approaches to Characterise Clonal Haematopoiesis
… through the interception of premalignant clones. Achieving this goal requires that several key challenges are overcome, including: the scalable identification of individuals with high-risk clones, the accurate stratification of CH subtypes most strongly linked to progression, and the …
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A Role for PI31-Mediated Proteasome Regulation in Proteostasis and Neuronal Health
… and proteasome activity. Generation of dmPI31 mutant clones in the Drosophila eye show rapid degeneration of photoreceptor cells and RNAi knockdown of DmPI31 leads to eclosion defects and shortened lifespan. I demonstrate the ability of NAD+ repletion to increase proteasome activity and DmPI31 …
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Somatic Mutations in Ageing and Degenerative Disease
… studies to directly investigate the role of mutant clones in disease states.
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Rapid Functional Dissection of Genetic Networks Via RNAi In Mouse Embryos
… system as the generation of double or triple mutants is even more inefficient. To circumvent these limitations, I have developed and optimized a lentivirus-based strategy to achieve rapid manipulation of the mammalian epidermis in vivo. Using ultrasound-guided in utero injections of …
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Mechanism of Action Studies of Phenotypic Whole-cell Active Antimalarial Leads Through Target Identification
… selection. Whole-genome sequencing of the mutant clones generated from KP68 under drug pressure showed a single nucleotide polymorphism in the mitochondrion carrier protein. It also revealed a few copy number variations, including the deamplification of the mitochondrialprocessing peptidase …
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Oncogenic KRAS drives heterogeneity in metabolic and signalling pathways through genetic and non-genetic mechanisms
… the other hand, cell-to-cell variability within mutant clones might permit a population of cells to escape tumour suppressive mechanisms such as senescence and adapt to oncogenic signalling, therefore supporting early cancer development. We have combined cell genetics, single-cell biochemistry …
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