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 14 of 14 for “"phenotypic screen"”.
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Small-Molecule Activation of Yap for Inner-Ear Regeneration – and Beyond
… in mature organs. Using a highthroughput phenotypic screen, we have identified a potent, non-toxic, and reversible inhibitor of Hippo signaling. An ATP-competitive inhibitor of Lats kinases, the compound causes Yap-dependent proliferation of murine supporting cells in the inner ear, murine …
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Discovery and biological evaluation of ferroptocide
… traits different from those in most screening collections, and as such are a rich source for biological discovery. Herein, we subject the complexity-to-diversity library of compounds to an anticancer phenotypic screen. This effort resulted in identification of an active class of …
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Mangrolide A, A Novel Marine Derived Polyketide with Selective Antibiotic Activity
… mangrolide A, which was discovered though a phenotypic screen against Burkholderia cepacia. Mangrolide A has selective activity against gram negative bacteria. The determination of the absolute stereochemistry of mangrolide A is described in chapter 3. In chapter 4, a new method to increase …
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Design and Synthesis of Antimycobacterial Agents
… progress has been tepid with target-based screens of synthetic and structurally conservative compound libraries failing to produce new therapeutics. This has led to a renewed interest in utilising phenotypic screens, but rather than applying them to natural product libraries and running the …
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Development of poly(ADP-ribose) glycohydrolase inhibitors and tetracyclic indoles as anticancer compounds
… potent anticancer tetracyclic indoles through a phenotypic screen. PARG plays a crucial role in DNA damage repair, and lack of PARG activity after DNA damage prevents repair and causes a build-up of toxic PAR chains. As such, PARG inhibitors have been pursued for decades as anticancer compounds. …
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Investigating novel treatment approaches to combat Clostridioides difficile
… we exploited the strategy of high-throughput screening to identify leads that harbor anticlostridial activity. Our primary phenotypic screen of FDA-approved drugs and natural product libraries led to the identification of novel molecules that were further characterized for their …
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A CHARACTERIZATION OF SELECTION FOR EVOLVED RESISTANCE TO PROTOPORPHYRINOGEN OXIDASE (PPO)-INHIBITING HERBICIDES IN AMARANTHUS TUBERCULATUS
… on RS individuals, a large-scale genotypic and phenotypic screen of multiple PPO-R waterhemp populations was conducted. It was determined that RS individuals were less frequent than expected and PPO-inhibiting herbicide efficacy on RS individuals was population-dependent. Finally, the hormetic …
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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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Defining the Transcriptional and Epigenetic Signature of Mouse Embryonic Stem Cells with Compromised Developmental Potency
… cell surface markers were analysed in a phenotypic screen using phage display. NGS analysis of the phage outputs indicates that there may be additional differences in cell surface markers between the control and compromised ES cell clones, but their specific details remain to be …
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Decoding Disease Drivers Through Single-Cell Omics and Scalable Phenotypic Screens
… then present a potential solution for performing phenotypic screens at scale. In the first part, I applied single-cell RNA sequencing and analysis to human lung samples from a TB-endemic region in South Africa. Using contrastive analysis, I identify key cell populations that are differentially …
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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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Cyclic di-GMP signalling and the regulation of virulence, biofilm formation and epiphytic fitness in the phytopathogen <i>Xanthomonas campestris</i>
… was used to verify the functionality of these phenotypic assays. The phenotypic screen revealed differences between each mutant and the wild type. Based on these results and the analysis of the virulence assays, five genes were chosen for the further work: <i>XC0362</i>, <i>XC1755</i>, …
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Small Molecules and Their Conjugates with Peptides: Chemical Strategies to Tackle Resistant Bacteria
… relationship of a compound identified in a phenotypic screen of a library of compounds made by diversity-oriented synthesis. The focus of this part is a different bacterium, *Mycobacterium abscessus*. The importance of targeting this bacterium is high as the strain is commonly found in the …
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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 …