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 97 for “"essentiality"”.
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Essentiality and Regulation of Deoxyhypusination in Trypanosoma brucei
… of recombinant DHSc by 3000-fold. While the essentiality of eIF5A and DHS is consistent with other eukaryotes, the finding that the functional DHS complex is composed of an impaired catalytic subunit (DHSc) and a catalytically dead paralog (termed a prozyme) is novel. This mechanism …
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Essentiality of Mitochondrial Genome Integrity in Cell Survival
The mitochondrial genome encodes 22 tRNAs, 2 rRNAs, and 13 polypeptides that are subunits of the electron transport chain involved in oxidative phosphorylation. Because of its proximity to source of ROS generation and its non-chromatinized structure, mitochondrial genome is continuously challenged …
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Synthetic Essentiality of Tdo2 In Apc-Mutated Colorectal Cancer
… other cancers. Using the concept of synthetic essentiality (SE), we</p> <p>sought to identify essential effectors of APC deficiency with the goal of</p> <p>expanding targetable vulnerabilities in CRC. We identified Tryptophan 2,3-</p> <p>dioxygenase 2 (TDO2) as an SE gene for APC-deficient …
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The Cell-Essentiality of KAT7 in Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy, characterized by the uncontrolled proliferation and differentiation arrest of myeloid progenitors. Chemotherapy has been the front-line treatment for decades and cure remains elusive for the majority of AML patients. …
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Investigating the Molecular Mechanisms Underlying Ku Essentiality in Human Cells
… human cell viability but is dispensable in mice. Essentiality in human cells was previously suggested to be due to Ku’s role in maintaining human telomere length. To study the underlying cause of Ku’s essentiality in humans, a conditional Ku70 knockout TREx-293 cell line was created using …
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Identification of Trim24 Domain Essentiality In Primary Trim24Coe Carcinosarcoma Cell Lines
… B Box and Coiled-Coil domains of TRIM24 showed essentiality in both of our cell lines in our screen. To computationally validate our findings, we performed a systematic analysis of other publicly available datasets including Project Achilles and DepMap to find similar TRIM24 dependencies and …
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Inferring context-specific essentiality networks using large-scale CRISPR-KO screens
… approaches to understanding context-specific essentiality networks. I developed a Bayesian linear model called PLMCECS which identifies genes important in the context of cancer driver mutations and tissue of origin by modelling important properties of CRISPR knockout data. I validated the …
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The dietary essentiality of n-3 polyunsaturated fatty acids in infant nutrition
Docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6) are deposited in large amounts in membrane phospholipids of the developing central nervous system (CNS). High levels of 22:6n-3 are found in synaptic terminals and retina, and are important for normal visual development and function. …
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Siding with Euthyphro : response-dependence, essentiality, and the individuation of ordinary objects
(cont.) essentiality. I start with our practices of engaging in thought experiments about the essences of things and show how my account vindicates those practices.
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Insights Into The Reactivation, Regulation and Essentiality of Oxidative Protein Folding Pathways In Actinobacteria
<p>Accurate disulfide bond formation is important for proper folding, stability and function of exported proteins. The process of disulfide bond formation, termed oxidative protein folding, is catalyzed by thiol-disulfide oxidoreductase enzymes. Oxidative protein folding pathways influence …
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Mice Lacking Delta -6 Desaturase Provide New Insight Into the Essentiality of Highly Unsaturated Fatty Acids
This knockout mouse presents itself as an ideal model for the continued investigation of HUFA including AA, DHA and DPA.
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Using machine learning to understand the link between gene essentiality, gene expression and the chemosensitivity of cancer cells
The emergence of pharmacogenomics databases has presented unique opportunities to leverage machine learning in precision medicine, particularly in drug response prediction. In this thesis, an in-depth investigation is conducted on carefully curated and integrated breast cancer focused datasets from …
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The essentiality of DivIVAEf oligomerization for proper cell division in enterococcus faecalis and interaction with a novel cell division protein
… lethal phenotype. These results demonstrate the essentiality of the N-terminal coiled-coil and oligomerization of DivIVAEf for its proper biological function in E. faecalis cell division. Previous detection of DivIVA interaction with a novel cell division protein, MLJD1, by screening a Yeast …
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Essence and Ontology
<p>This dissertation provides an account of essentiality that satisfies two main desiderata:</p><p>(1) The account should offer an explanation as to why the following two intuitions are true:</p><p>(i) It is essential to the set {Socrates} to have Socrates as a member.</p><p>(ii) It is not …
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Inquiries into the Mycobacterial Caseinolytic Protease System
… by the Clp system and contribute to its essentiality. By complementing knockdown of endogenous clp components with CRISPRi-resistant alleles encoding biochemically functional mutations, we unexpectedly found that only the proteolytic activity of ClpP1, but not ClpP2, is essential for Clp …
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The role of dietary arachidonic acid and docosahexaenoic acid in preventing the phenotype observed with highly unsaturated fatty acid deficiency
… prevented by either AA or DHA (Chapter 5). AA essentiality was specific to skin and gastrointestinal function since DHA supplementation was unsuccessful in preventing ulcerative dermatitis or gastrointestinal ulcers (Chapter 6). DHA essentiality was specific to male reproduction as indicated by …
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Modelling fitness and stability of G protein-coupled receptor variants
… and improve the understanding of GPCR gene essentiality and gene-disease links4. Recently, machine learning (ML) models have made significant advances in protein structure prediction5 and variant effect prediction6. However, use of ML models in high-stakes decisions is challenging as the …
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Investigating the biosynthesis of the streptomycete antibiotic pacidamycin
… Pac17 active site amino acids also showed their essentiality for aspartate binding. In vitro biochemical approaches to study the enzymatic activity of the DABA biosynthetic proteins were inconclusive, with no activity observed. Genetic disruptions of the genes under investigation revealed the …
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The Impact of Depleting the Essential Bacterial Enzyme Peptidyl-tRNA Hydrolase on Translation
… and brings longstanding beliefs about the essentiality of Pth into question. We used genome-wide techniques to characterize the effects of the loss of Pth on translation and searched for factors that can compensate for its depletion in Escherichia coli to expand our understanding of the …
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Identification and Characterization of Drug Targets in the Pyrimidine and Purine Pathways of Trypanosoma brucei
… enzymes. Specifically, my research validates the essentiality two seemingly redundant enzymes: thymidine kinase (TK) and cytidine deaminase (CDA). Using a combination of genetic and analytical techniques, a novel pathway linking cytosine and thymine nucleotides was discovered. This pathway is …
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