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 22 for “"Disease mutations"”.
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Familial Alzheimer's Disease Mutations in Presenilins Disrupt Endoplasmic Reticulum Calcium Leak
Alzheimer disease (AD) is the most common form of progressive dementia in adults over the age of 65 years. AD is a fatal brain disease and it currently affects about 27 million people worldwide. It is speculated that the number of people affected by AD will quadruple by 2050. The presence of …
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Engineering Hv1 Channel Mutations and Targeted Drug for Treatment of Hv1 Mutation Associated with Cancer
… Dysregulation of Hv1 is associated with various diseases, including cancer, where it helps maintain an acidic tumor microenvironment that promotes tumor progression, metastasis, and apoptosis resistance. Additionally, genetic mutations in Hv1 have been linked to several diseases, with growing …
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Systemic analysis of changes in protein modification and gene coexpression networks in cancer
… altered PTM landscapes on a large scale, disease-associated mutations from TCGA, Uniprot, and dbSNP were integrated with PTM sites from PhosphoSitePlus. We characterized each dataset individually, compared somatic with germline mutations, and analyzed PTM sites intersecting directly with …
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MODELLING GBA1-RELATED PARKINSON¿S DISEASE PATHOLOGY IN PATIENT-DERIVED MIDBRAIN ORGANOIDS
… key neuropathological hallmarks of Parkinson’s disease. Mutations in GBA1, encoding the glucosylceramide-hydrolyzing enzyme glucocerebrosidase, cause Gaucher’s disease and are the most frequent genetic risk factor for Parkinson’s disease. However, a defined link between mutations in GBA1 and …
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Solution structure and biochemistry of an intramembrane aspartyl protease (IAP)
… been implicated in the pathogenesis of human diseases, such as Alzheimer’s disease, Hepatitis C, malaria and a variety of cancers. Despite their broad medical and biological relevance, structural and mechanistic details of IPs have remained largely obscure. A continuous FRET peptide assay, …
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TREX1 C-Terminus Regulates Oligosaccharyltransfererase to Prevent the Accumulation of an Endogenous Bioactive Disaccharide Associated with Autoimmune Disorders
… TREX1 localization to the surface of the ER. Disease mutations that abrogate the N-terminal DNase function of TREX1 lead to chronic activation of CDS-mediated innate immune response to self-DNA ligands leading to autoimmunity.In contrast, disease mutations in the C-terminal region are mostly …
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Development of a novel screening platform for identifying genetic pathways regulating axon regeneration
… approach to understanding the loss-of-function disease mutations. Due to its many advantages, CRISPR technology is an attractive tool to irreversibly remove the gene of interest by targeting its DNA. The overall goal is to identify negative regulators in axon regeneration. Here, we performed …
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Kap-[beta]2 Recognition of Cargoes Involved in Neurodegenerative/Neurodevelopmental Diseases
… of Kapβ2 cargoes are mutated in neurological diseases. Two such proteins of interest to my research are the Fused in Sarcoma (FUS) and the HNRNPH2 proteins that are mutated in familial ALS and Bain disease, respectively. I studied the interactions of Kapβ2 with HNRNPH2, which is mutated in the …
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The human myeloproliferative disorders: molecular pathogenesis and clonal heterogeneity
… neoplasms associated with activating mutations in signalling pathway molecules and a variable tendency to develop acute myeloid leukaemia (AML). This thesis examined genotype-phenotype associations of JAK2 and MPL mutations, the presence of clonal diversity in the MPD and the genetic …
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Modelling neurodegenerative diseases in human iPSC-derived neurons
… is a pathology shared by a varied class of diseases, and many of the mutations that are known to cause such diseases have been linked to protein aggregation and autophagy dysfunction. Improvements to gene editing and neuronal differentiation strategies have enabled the derivation of in vitro …
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Alu retrotransposition-mediated genomic variation within the primate order
… (pTPRT). Approximately 0.27% of all human disease mutations are attributable to the activity of Long INterspersed Element (LINE) L1, Alu and SVA (SINE-R/VNTR/Alu) retrotransposons within our genomes. Although researchers in the field of human genetics have discovered many mutational …
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Network based analysis of genetic disease associations
… the genetic factors contributing to common human diseases. There are many theories about where this "missing heritability" might lie, but increasingly the prevailing view is that common variants, the target of GWAS, are not solely responsible for susceptibility to common diseases and a substantial …
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Combination Chemotherapy and In vivo Modeling of BRCA-deficient, High-grade Serous Ovarian Cancer
… with over 60% of patients succumbing to the disease. Mutations in a number of homologous recombination repair genes have been implicated in hereditary ovarian and breast cancer. Specifically, over half of ovarian cancer cases exhibit BRCA-deficiency by either germ line or somatic mutation, or …
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Identification and Application of Novel Therapeutic Targets for PRPH2-Associated Disorders
Mutations in the photoreceptor specific tetraspanin Peripherin-2 (PRPH2) are some of the most pervasive pathogenic inherited retinal disease mutations with over 200 identified. Lack of an FDA approved treatment, numerous low prevalence mutations, and complex pathogenic mechanisms make it imperative …
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Structural Studies into the Mechanism and Organisation of Mammalian Respiratory Complex I
… as a system for studying human complex I disease mutations and its unique metabolic adaptations. Chapter 2 uses structural data from two high-resolution cryo-EM datasets (each up to 2.2 Å) of mammalian complex I in induced protonated and deprotonated states at a pH range where the enzyme …
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Genetic analysis of dynein function in the nervous system and in mitosis
… of this motor is underlined by the fact that mutations in Dynein heavy chain, the motor-containing subunit of dynein, cause neurological disorders in humans. How dynein exerts its diverse roles in healthy cells, and how defective motor function causes disease, are not well understood. In this …
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Single-Molecule Studies of CFTR Gating and Pharmacology
… disrupt activity cause cystic fibrosis, a fatal disease which is characterized by systemic salt and fluid dysregulation. By contrast, hyperactivation of CFTR is central to pathogenesis in secretory diarrhea and autosomal dominant polycystic kidney disease. Electrophysiological properties of CFTR …
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Improving Collagen-Mimetic Fibrils to Study Fibrillogenesis and Effects of Disease-Causing Mutations on Fibrillogenesis
… The need to study collagen further stems from a disease perspective, as mutations in collagen lead to numerous connective tissue diseases. While collagen has been explored extensively at the triple helix level, much remains undiscovered regarding its function at the fibril level due to the lack …
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Regulation of the Parkin E3 ligase by PINK1-dependent phosphorylation
Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting around 1% of the population over the age of 65 worldwide. While the majority of cases are sporadic, groundbreaking genetic research over the last two decades has revealed a complicated network of genes …
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Biochemical characterisation of the Parkinson's disease-associated kinase PINK1: Insights from the insect world
Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting approximately 1% of the population over the age of 65. Around 5% of these cases can be linked to mutations in known genes, one of which is the PINK1 gene, first linked to PD a decade ago. Since then, over 30 …
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