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 25 for “"cell fitness"”.
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GATA1 Occupancy Site Regulates Erythroid Cell Fitness through Pleiotropic Functions
… how non-coding variants influence cellular function remains a significant challenge in genetics, largely due to limited knowledge about regulatory sequence grammar, complex chromatin environments, and the transcriptional regulatory networks that link genotype to phenotype. In this …
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An in vivo evaluation of aneuploid hematopoietic stem cell fitness
Aneuploidy is an unbalanced cell state associated with developmental conditions such as Down syndrome (DS) as well as cancer, a disease of rapid proliferation. Studies of yeast, mouse and human cells harboring one extra chromosome have demonstrated that aneuploid cells show a number of common …
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Investigating aneuploidy's role in cancer cell fitness under various conditions of stress
… is a distinguishing feature of cancer cells. The rapid gain or loss of hundreds of genes dramatically alters a cell's genomic landscape and is typically detrimental to cell survival under normal conditions. However, cancer cells display enhanced proliferation and overcome multiple …
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Characterizing the landscape of aminoacyl-tRNA synthetase protein production in Bacillus subtilis
The phenotype of a cell is a consequence of both the identity of the genes in the genome and the magnitude of their expression into proteins. While the biochemical function of many proteins has been uncovered, for most it is unclear how important native protein abundances are for cell fitness. …
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Examining the Regulation and Function of Cancer Testis Antigens
… to the testis, but are reactivated in cancer cells. The function and regulation of many CTAs are unknown, however several CTAs have been shown to impact tumor cell fitness and correlate with poor prognosis. Our lab became interested in CTAs after a pan-genomic-loss-of-function RNAi screen …
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Global and chromosome-specific consequences of aneuploidy in Saccharomyces cerevisiae
… or reduced copy number, causes an array of known cellular phenotypes including proteotoxicity, genomic instability and slowed proliferation. Organisms with constitutional genomic imbalance are less fit than their euploid counterparts, and aneuploidy is the leading cause of spontaneous abortion in …
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Investigation of Proliferation Suppressors In Genetic Fitness Screens
… screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities …
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The Benefits and Detriments of Aneuploidy in Cancer
… are aneuploid. How does aneuploidy affect cancer cells? These copy number alterations affect expression at the RNA and protein level, which causes numerous problems for cells. Aneuploidy increases genomic instability, both through higher rates of DNA damage and causing more chromosome …
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Functionality of mutant p53 in early tumorigenesis
… but it may uncover how the mutation primes a cell for aberrant activities. By modelling the heterozygous expression of p53R175H in unstressed, acute- and chronic-stress conditions (DNA damage induced senescence, DDIS), I have identified potential DN and GOF activities and the underlying …
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Regulation of Breast Cancer Initiation and Progression By 14-3-3Zeta
… reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly, new evidence has emerged that …
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The circadian Control of DNA end Resection
… (DSBs) stand as the most cytotoxic lesion the cell can endure, they have evolved two major pathways to counter these: the religation of the broken ends (Non-Homologous End-Joining, NHEJ) and the repair of the lesion using a homologue sequence (Homology-Directed Repair, HDR). The choice between …
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Exploring the role of the arginine-methylation writer-reader pair PRMT5/SND1 in JAK2-mutant myeloproliferative neoplasms
… disease characterized by hyperproliferation of cells of the myeloid lineage for which current therapeutic options are limited. Discovered in 2005, the JAK2V617F mutation is the most common driver mutation in BCR-ABL negative MPNs, resulting in constitutive activation of the JAK2 protein and the …
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Insights into the consequences of chromosome gains and losses in S. cerevisiae
When cells divide, they must properly duplicate and segregate their genome to generate two identical daughter cells with faithful transmission of the genomic content. Errors in chromosome segregation lead to aneuploidy, a state of chromosomal imbalance where the karyotype is not an exact multiple …
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Novel immunotherapy for paediatric cancers
… T lymphocytes to specific tumour antigens. CART cells targeting CD19 (CAR19) have demonstrated remarkable efficacy against B cell malignancies in clinic. Currently used methods of CAR gene transfer to T cells based on viral vectors are complicated by the time and expense involved in the elaborate …
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The Current Role of Kynurenine Pathway Interventions in Oxidative Stress and Redox Homeostasis in the Context of Aging and Cancer
… –the main route to metabolize tryptophan in the cell– has emerged as a therapeutic target in several age-related diseases, including cancer. Intermediate metabolites in the kynurenine pathway have immunological and redox properties that have been associated with cancer initiation, progression, …
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Determining how variations in cell and nuclear size contribute to mitosis and tumorigenicity in cancer cells that undergo whole genome doubling
… leads to the accumulation of aneuploidy in human cells and is sufficient to induce tumorigenesis in mice. While the genomic effects of WGD are well established, the morphological alterations that accompany WGD, such as changes to cell and nuclear size, and their functional consequences are less …
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Exploiting Chemogenetic and Genetic Interactions In Human Cells As An Avenue For New Therapeutic Opportunities
… 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 essential genes and provide insights into disease-specific candidate therapeutic targets. …
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Utilizing Haplotypes For Sensitive Snp Array-Based Discovery of Somatic Chromosomal Mutations
… and high levels of contaminating normal cells in tumor samples, which limit the fraction of cells carrying informative mutations. The method presented here is the first method to utilize population-based haplotype estimates to discover low-frequency somatic kilobase- to megabase-size CN …
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Myc influences glutamine metabolism to induce autophagy in tumorigenesis
… and metabolic adaptation typical of tumour cells to support cell growth. One of the major players in this process is Myc, which can promote tumorigenesis by triggering a metabolic reprogramming that allows cells to produce macromolecules, by modulating glycolytic flux, glutaminolysis, …
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Unifying the features that determine substrate preferences of nanoRNases
… degraded, and modified through several varied cellular processes. The ability of cells to degrade and recycle their RNA products is a ubiquitous and essential function. Specific subsets of endo- and exoribonucleases catalyze the reactions that ultimately replenish the pool of …
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