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 “"Organoid models"”.
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Characterisation of human enteroendocrine cells in organoid models
… of gut motility which is not expressed in rodent models) and serotonin (5-HT, a monoamine neurotransmitter with wide-ranging effects within and outside the GI tract). Several in vitro models have been developed to study the mechanisms of EEC regulation; however, at the outset of this project, it …
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Investigating circuit and spatial heterogeneity of human brain tumors with patient-derived organoid models
… heterogeneity by leveraging patient-derived GBM organoids (GBOs), a 3-dimensional model inspired by human brain organoids. In the first sections of this dissertation, I describe the application of circuit neuroscience techniques to study diverse tumor-neuron circuitry. Previous studies discovered …
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A study of the causes and consequences of SFTPC mistrafficking in alveolar type 2 cells using novel organoid models
… by developing a genetically manipulable alveolar organoid model in which to test the consequence of ITCH depletion. Using this novel organoid system, I then generated models of both inducible exogenous SFTPC-I73T expression and its endogenous expression using base editing. These heterozygous …
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Exploring the role of BCL11A in the oesophagus and mammary gland using in vivo lineage tracing and 3D organoid models.
… vivo lineage tracing techniques and in vitro 3D organoids to explore the expression and gene function of Bcl11a in the oesophageal epithelium and mammary gland. Gene function studies were undertaken using mouse models of BCL11A overexpression: RosaCreERT2; Rosa-CAGG-LSL-BCL11A (BCL11AOE) and …
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Human Brain Organoids for Studying Malignant Cell States and Intercellular Communication in Human Glioma
… within these tumors; it follows that appropriate models for studying glioma behavior and progression – and, in turn, therapeutic avenues – must adequately recapitulate these key features. Indeed, patientderived tumor xenografts (PDXs) are, for this reason, attractive and widely used in vivo model …
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Cardiac organoid technology and computational processing of cardiac physiology for advanced drug screening applications
… to explore the potentials of stem cell cardiac organoid models to recapitulate heart development and implement analytical computational tools to study cardiac physiology. These new tools were implemented as potential advancements in drug screening applications for better predictions of …
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The Role of Mesenchymal Cells in the Regeneration of Salivary Gland Tissue
… particularly when developing cell cultures and organoid models. 23 In order to investigate the impact of PSS on the ability of cells to proliferate and perform a rudimentary regenerative function, the group developed cell cultures that were representative of epithelial and mesenchymal cell types …
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OrganixInsights: High throughput imaging and high content screening of organoids
… In particular, three-dimensional (3D) organoid models have emerged as powerful experimental systems for investigating tissue development, disease progression, and therapeutic response. Organoids replicate key structural and functional characteristics of in-vivo tissues, including …
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DISSECTING THE ROLE OF Β-CATENIN AND MYC IN GASTRIC TUMOR FORMATION
… Here, using conditional transgenic mouse models, we show that Wnt constitutive activation does not have any oncogenic effect in the gastric epithelium and cooperates with MYC in driving gastric tumorigenesis. By integrating transcriptomic and epigenomic analysis with organoid models, we …
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Towards using organoids in functional genomics – A single cell characterisation of mouse gastruloids
… to perform such studies at scale in vivo, organoid models of mouse gastrulation are now making them possible. This thesis concerns the characterisation of an organoid model of mouse gastrulation called gastruloids, as a model for such perturbation studies. Gastruloids are grown by …
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The role of APC in cellular and tissue organisation in intestinal tumorigenesis
… various genetically modified 3-dimensional organoid models to study the role of APC in malignant transformation of the intestinal epithelia. I show that APC inactivation leads to alterations in tissue morphology. Intriguingly, my results reveal a novel phenotype upon loss of APC resulting in …
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CGRP family of G protein-coupled receptors and their signalling in human cardiovascular cells
… the functional outcomes of signalling in cell organoid models are all explored. It is the author’s belief that this work adds a great deal to the understanding of the CLR, and more generally takes a step forward in the understanding of endogenous GPCR signalling bias.
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Hypoxia signalling regulates human lung epithelial cell fates
… hypoxia on the human lung epithelium using organoid models. Human first-trimester lung epithelial progenitors can be isolated from embryonic and fetal lungs and expanded in an undifferentiated state when culturing in the self-renewal medium under normoxia (around 20% O2). In physiological …
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Comparative studies of brain developmental timing and progression using 3D stem cell models
… or interventions. We used self-organising brain organoid models, derived from stem cells of different relevant species to establish paradigms for comparative studies in brain development, and understand aspects of human specific brain development in vitro. In order to make fair comparisons …
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Creation of organoid systems to model human endodermal organ development in vitro
Organoid systems have revolutionised the study of adult stem cells and organ homeostasis. However, there have been limited attempts to use the technology to study human organ development. The work of this thesis established two novel hepatic organoid systems; one based upon the archetypal liver …
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Ribonucleotide Reductase Subunit Switching in Hepatoblastoma Drug Response and Relapse
… of high-risk HB. Our recent work on HB mouse and organoid models, patient-derived xenografts (PDX) and primary patient samples revealed a significant upregulation of ribonucleotide reductase (RNR) subunit M2 (RRM2) in high-risk HB. RNR is the sole enzymatic complex in mammal cells that converts …
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3D KIDNEY ORGANOIDS AS A PLATFORM FOR INVESTIGATING MONOGENIC DISEASES AND GENE THERAPY APPROACHES
Abstract The use of 3D in vitro models is now widely adopted in biomedical research. These models enable the study of human cells under more physiologically relevant conditions and allow for early proof-of-concept testing of therapies prior to animal studies. While 3D models do not replace …
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Reconstructing Chromothriptic Chromosomes in Oesophageal Adenocarcinomas
… patient-derived oesophageal adenocarcinoma organoids with evidence of chromothripsis restricted to one allele were used to better understand how the genome is regulated. Complex regions of structural variation between alleles in cancer genomes coupled with subclonal variants means …
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Specific forms of TCF7L2 protein define the Wnt pathway dependent genetic program
… systems to study TCF7L2 expression levels using organoid models. The technology consisted of organoids cultured in media containing precise activities of essential growth factors, obviating issues endemic to the use of commercially sourced, impure growth factor preparations. I focused on the two …
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Clonal Dynamics in Barrett's Oesophagus and Oesophageal Adenocarcinoma
… in vivo model for BO/OAC, but patient derived 3D organoids may provide an appropriate in vitro system for studying clonal dynamics, including competition between different stages of the disease. The evolution of IM through to OAC is still being explored. To date we know that progression is …
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