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 29 for “"intestinal organoids"”.
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Modeling colorectal cancer initiation using human iPSC-derived intestinal organoids
… pluripotent stem cell (hiPSC)-derived human intestinal organoids (HIOs) are increasingly utilized as in-vitro models for studying colorectal cancer (CRC). Prevalent oncogenic drivers in CRC include mutations in EGFR (L858R), KRAS (G12D) and CTNNB1 (S33C) which are known to contribute to …
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Exploring the function and sensing mechanisms of human enteroendocrine cells using intestinal organoids
… such as nutrient digestion and absorption, intestinal motility, food intake, inflammation, and energy homeostasis. This thesis aimed to characterise hormone-releasing sensing mechanisms adopted by two important types of EECs: K-cells, which secrete glucose-dependent insulinotropic …
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Modelling the interactions of Salmonellae with the human host using stem cell-derived intestinal organoids and macrophages
… interactions has been developed; known as “organoids” or human intestinal organoid systems (iHO). These can be produced from human induced pluripotent stem cells (hiPSCs), or from primary intestinal tissue, and once matured, harbour differentiated enterocytes and secretory cells such as …
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Host-Pathogen Interactions at the Intestinal Epithelial Barrier
… investigations of the interactions between the intestinal epithelial barrier and the intracellular apicomplexan Eimeria spp., both in vivo and in vitro. Initially, conventional in vivo studies using genetically modified animals were used to investigate the contribution of innate lymphoid cells …
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An integrated system for selection and manipulation of single cells in culture
… This system was then applied to study intestinal organoid formation. Specifically, current protocols for the production of intestinal organoids suffer from low yield, with only ~12% of the highly heterogeneous nascent spheroids successfully maturing into intestinal organoids. It was …
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To Investigate The Impact Of Gut Bacteria On Efflux Transporter Expression And Function In Gastrointestinal Mucosae
… breast cancer resistance protein (BCRP) using intestinal organoids derived from germ free and humanized mice. Typically, transport across the epithelial cell layers occurs by active transport and passive diffusion. Using mouse models that differ in bacterial content and fluorescence scanning, …
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Creation of organoid systems to model human endodermal organ development in vitro
… of the human intestine, characterising how intestinal organoids develop in vitro, and going on to assess human intestinal maturation in vivo at single cell resolution. First, the developing human liver was characterised during the first trimester and the cellular composition at this crucial …
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Phenotypic characterisation of wild type and mutant strains of adherent invasive Escherichia coli and Shigella, in vitro, ex vivo and in vivo models
… to antibiotics appears to be a factor in gastrointestinal diseases. Therefore, the present study sought to evaluate the key AIEC and Shigella sonnei virulence genes for their pathogenic roles and to address the problem of antibiotic resistance and also prevent the destruction of beneficial gut …
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CRISPR gene editing for Cystic Fibrosis: targeting the G542X mutation with base editor engineered virus-like particles
… rescued the mutation in patient-derived intestinal organoids, and prompted further investigation into the eVLPs. Two titration assays and a luminescence-based reporter system were established to standardize and monitor particle-mediated transduction. Finally, extending the G542X-editing …
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Developing novel prophylactic approaches against SARS-CoV-2 infection
… COVID19- affected tissues, including the gastrointestinal and respiratory systems. I use this knowledge to optimise current experimental models for SARS-CoV-2 infection and I demonstrate that reduction of FXR signalling, with the over-the-counter compound z-guggulsterone (ZGG) and the off-patent …
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Microbiota regulate short chain fatty acids and influence histone acylations in intestinal epithelial cells.
The intestinal microbiota have a vital role in aiding digestion by metabolising dietary fibres. In this process, they produce short chain fatty acids (SCFAs) such as butyrate, an important energy source for intestinal epithelial cells. SCFAs are chemically related to histone acylations, a growing …
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Activation and Maintenance of Intestinal Intraepithelial Lymphocytes (IELs)
The intestinal tissue is charged with a delicate immunological task. The intestinal immune system needs to be tolerant towards nutrients and microbiota present in the intestinal lumen, while simultaneously detecting and responding to dangers such as pathogens. A single-cell layer of intestinal …
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Paneth Cell-Dependent Intestinal Homeostasis During T. Gondii Infection
The intestinal epithelial barrier faces the arduous task of constantly monitoring and controlling the diverse bacteria which colonize the gut. Key for this balance are the Paneth cells, highly specialized secretory epithelial cells in the intestinal crypts which secrete anti-microbial peptides to …
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Investigating the movement of intestinal intraepithelial lymphocytes using an organoid co-culture system
… intestine, which is lined by a single layer of intestinal epithelial cells, is the main site of nutrient absorption. It is continuously exposed to food antigens, and also several bacteria and microorganisms. Intestinal intraepithelial lymphocytes (IELs) are T cells that are interspersed between …
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Abrogation of serine metabolism exacerbates intestinal epithelial inflammation via C/EBPβ-NF-κB pathway
… inflammation and metabolic dysregulation in the intestinal epithelium. Serine, a non-essential amino acid synthesized via the rate-limiting enzyme phosphoglycerate dehydrogenase (PHGDH), maintains celular redox balance. Serine metabolism is upregulated in cancer and immune cells, supporting …
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Norovirus Translation and Replication
… tested in different cell types. The B-cell and intestinal organoids culture systems were validated. In addition, using organoids culture a DNA-based reverse genetic system was shown to recover infectious HuNoV. Due to the challenges associated with cultivating HuNoV, murine norovirus (MNV) was …
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ENGINEERING STEM CELLS AND ORGANOIDS ON A CHIP FOR THE STUDY OF HUMAN HEALTH AND DISEASE
… combine organs-on-a-chip technology with organoids to create human tissue models with increased biological and structural complexity. Specifically, we introduce a novel approach to enhance organogenesis in a dish through geometric engineering of organoid culture. Our approach allows …
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Targeting the intestinal stem cell niche through energy and metabolism signaling, for colorectal cancer chemoprevention using aspirin and metformin
… increases ‘stemness’: the ability of intestinal stem cells to self-renew or differentiate. The mechanistic target of rapamycin (mTOR) pathway, a central metabolic regulator, is elevated in CRC and modulates stem cell response to nutrients. Therefore, chemopreventive agents which …
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Antibody technology identifies distinct mechanisms controlling the lengths of filopodia-like structures
… retinal ganglion cell growth cones and mouse intestinal organoids. To verify the candidate proteins, I combined Western blotting against purified proteins, sedimentation assays with purified actin, immunostaining and transient expression of proteins of interest, confirming the identity of two …
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Characterisation of L-cell secretory mechanisms and colonic enteroendocrine cell subpopulations
… (EECs) are chemosensitive cells of the gastrointestinal epithelium that exert a wide range of physiological effects via production and secretion of hormones in response to ingested nutrients, bacterial metabolites and systemic signals. Glucagon-like peptide-1 (GLP-1) is one such hormone …
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