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 31 for “"Phenotypic screening"”.
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Towards ultrahigh-throughput phenotypic screening using microfluidic droplets and functionalised polyacrylamide beads
… platform on which to build. Ultrahigh-throughput screening offers researchers a powerful tool to begin sampling larger regions of sequence space, and thus partially addresses one of evolution’s main advantages. This approach has particularly grown in promise and scale as DNA sequencing has become …
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Phenotypic screening and AI uncovers modulators of YAP and TAZ activity in glioblastoma
… intra-patient heterogeneity. This is enhanced by phenotypic plasticity of tumour cells which allows them to differentiate and regress into multiple glial-like cell types with neoplastic traits and enhanced stem cell characteristics contributing to radio- and chemo-resistance. These stem-like cells …
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Construction and phenotypic screening of mid-size insert marine microbial environmental genomic libraries
Functional screening of environmental genomic libraries permits the identification of clones expressing activities of interest without requiring prior knowledge of the genes responsible. In this study, protocols were optimized for the construction of mid-size DNA insert, inducible expression …
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Functional miRNA-based Phenotypic Screening as a tool to delineate HIV-host interactions and facilitate Novel Drug Discovery
… unknown. A microscopy-based high content screening (HCS) approach was thus developed to systematically evaluate the significance of augmenting or inhibiting the function of individual host miRNAs on the replication dynamics of HIV. A bespoke image analysis and data mining pipeline …
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Investigation of global regulators influencing styrene metabolism and bioplastic synthesis in Pseudomonas putida CA-3
… genome. The library generated was subjected to phenotypic screening to identify mutants exhibiting a reduced sensitivity to the effects of carbon catabolite repression of aromatic pathway activity. Our efforts identified a clpX disrupted mutant which exhibited wild-type levels of growth on …
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Molecular target identification of antimalarial drugs using proteomic and metabolomic approaches
… MMV008138 as anti-apicoplast inhibitor through phenotypic screening. Preliminary data suggest that the molecular target of MMV008138 may be within the MEP pathway. We used proteomic and metabolomic approaches to identify the molecular target of MMV008138 to aid future medicinal chemistry to …
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Structure-based development of novel chemical scaffolds as inhibitors of the store-operated calcium entry pathway
… of the existing SOCE inhibitors originate from phenotypic screening and derivatisation of some initial hits that were not much selective against the SOCE (Orai-mediated) and non-SOCE (TRPCs-mediated) pathway. Recently, few structures of the Drosophila Orai (DmOrai) have been published and I …
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Computational Methods to Identify and Target Druggable Binding Sites at Protein-Protein Interactions in the Human Proteome
… of hit compounds from structure-based virtual screening. The tight uPAR•uPA interaction offers a platform to test methods that leverage hot spots on both the protein receptor and ligand. A method is described that enriches for small molecules that both engage hot spots on the protein receptor …
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Drug Repurposing Using Gene Expression Data Mining
… applications to drug repurposing and compound screening. This thesis focuses on addressing those challenges---I have developed several novel computational methods and have demonstrated their powers in discovering novel therapeutics for multiple diseases.</p> <p>First, we have designed a …
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Developing Low-GN and GN-zero Winter Malt Barley for the Eastern United States
… generation advancement and enable earlier GN screening in segregating populations. Of the 2,520 seeds planted from 12 GNzero crossed with adapted breeding lines F2:3 families, 103 heads were successfully harvested under extended photoperiod and controlled temperature conditions. These families …
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Antibody technology identifies distinct mechanisms controlling the lengths of filopodia-like structures
… of antibodies isolated by phage display antibody phenotypic screening on an *in vitro* system of filopodia-like structures (FLS) I aimed to discover new molecular mechanisms underlying filopodia formation. To identify the antigens of the phage display antibodies I combined Western blotting, …
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Characterizing the Activity of Three Novel Differentiation-Inducing Compounds in Neuroblastoma Cells
… available therapies. Using a high content phenotypic screening of a Chembridge small molecule library, three novel neurite-inducing small molecules (Compounds 3, 4, and 10) were identified. The objective of my study is to determine whether the hit compounds have a generic …
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MASS SPECTROMETRIC STRATEGIES TO IDENTIFY BIOACTIVE COMPONENTS FROM NATURAL EXTRACTS WITH ANTI-INFLAMMATORY ACTIVITIES
… integrating engineered cell cultures for phenotypic screening of bioactive extracts, Mass Spectrometric-based metabolomics to unravel the primary components of these extracts, and Mass Spectrometric-based proteomic studies to comprehensively analyse their impact on the cell proteome. The …
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Engineered approaches to querying the microenvironment of cancer metastasis
… development and use of a novel ECM microarray screening platform. This platform consists of 768 unique single and pairwise combinations spotted in quintuplicate as 150pm features onto polyacrylamide coated glass slides. Cells are seeded onto these arrays and queried for their adhesion, …
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SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL ANTIPARASITIC AND ANTICANCER AGENTS
… activity. For the second study, we conducted a phenotypic screening of an in-house compound library against Plasmodium falciparum, T. brucei, and two Leishmania species, leading to the identification of promising hit compounds featuring 1,3,4- and 1,2,4-oxadiazole scaffolds linked to a …
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Improved In Silico Methods for Target Deconvolution in Phenotypic Screens
Target-based screening projects for bioactive (orphan) compounds have been shown in many cases to be insufficiently predictive for in vivo efficacy, leading to attrition in clinical trials. Phenotypic screening has hence undergone a renaissance in both academia and in the pharmaceutical industry, …
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Creating effective drug discovery methods in Mycobacterium abscessus
… tools which overcome the limitations of phenotypic drug discovery, namely that there is limited information on how a compound works available when critical decisions of resource commitment are made. I identify hit identification and hit-to-lead progression as two key components of early …
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APPLICATION OF OMICS APPROACHES IN DRUG DISCOVERY AND BIOMARKER IDENTIFICATION
… Chapter 2, we integrated omics approaches into phenotypic screening drug discovery to support the identification of novel bioactive compounds. These studies aimed to apply untargeted multi-omics approaches to infer the mechanism of action of phytocomplex with potential lipid-lowering properties. …
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Cross-Modality Profiling of High-Content Microscopy Images with Deep Learning
… metadata labels freely obtained in high-content screening into deep learning architectures. The use of automated microscopy in high-content phenotypic screening of cells treated with compounds or genetic perturbations produces a large amount of high-dimensional data. One example which we focus on …
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An in vitro chemogenomic screening system to identify the molecular targets of antimalarial drug candidates
… therapies. A global effort to carry out phenotypic screening in live parasite assays has identified many promising hit compounds, but elucidating the targets of these compounds, often a necessary step in the hit-to-lead development process, has been slow. This is because target …
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