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.
Results
Showing 1 to 15 of 15 for “"CHEMICAL-GENETICS"”.
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Using a chemical genetics approach to dissect the nitrogen signalling pathway in Arabidopsis
… This project, for the first time, adopts a chemical genetics approach to investigate the feedback regulatory pathway that links the plant’s N status to expression of the NRT2.1 nitrate transporter gene. A novel chemical screening platform was developed that was designed to be used in …
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Discovery of novel antibacterial and antitubercular compounds using chemical genetics and computational approach targeted at phospholipid biosynthesis
… biosynthesis pathways. Genetic and biochemical studies carried out on phosphatidylserine synthase (Pss) and phosphatidylserine decarboxylase (Psd) demonstrated the essentiality of these membrane proteins in S. coelicolor. Alteration of pss expression affects the overall growth and …
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Using Small Molecule Tools to Study ATPase Mechanoenzymes
… mechanoenzymes has been linked to diseases, and chemical inhibitors and activators can be powerful tools to probe mechanisms and test therapeutic hypotheses. However,the structural conservation across the AAA protein family makes designing selective chemical inhibitors challenging. Additionally, …
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Characterization of novel genetic alleles of cellulose synthase
… little is known about the proteins and biochemical mechanisms governing cellulose biosynthesis. Only in the past 10 years since the sequencing of the Arabidopsis thaliana genome have we begun to unravel the full complexity of this process in plants. A chemical genetics screen using the …
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Functional Analysis of KAP1 Requirements for HIV-1 Transcription and Latency Reactivation
… KAP1 transcription regulatory functions using a chemical genetics strategy to acutely deplete KAP1 expression to avoid the accumulation of indirect effects. KAP1 acute loss dampened HIV-1 promoter activity in response to activating signals, a function that can be restored upon complementation …
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Interactome Analysis Identifies Novel Targets of Phosphoinositide 3-kinase (PI3K) that Mediate Astrocyte Neuroprotection
… this activity remained unclear. Here, a chemical genetics screen revealed phosphoinositide 3-kinase (PI3K) as a central player transducing ACM-mediated neuroprotection. To identify additional proteins contributing to the protective activity, endogenous neuronal PI3K was immunoprecipitated …
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Diverse roles for the mitogen-activated protein kinase ERK2 revealed by high-throughput target identification
… targets are reported frequently. We have used a chemical genetics approach to identify over one hundred novel substrates of ERK2. This approach utilizes an ERK2 kinase with "gatekeeper" mutation that allows it to bind bulky ATP analogs (AS-ERK2). AS-ERK2 can be used to label its direct substrates …
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A study of the mechanism of action of novel inhibitors of tumour cell invasion
… aspects of metastatic progression. A forward chemical genetics project was initiated in an effort to identify novel compounds that inhibit tumour invasion. After screening a natural extract library, two novel inhibitors were identified: motuporamine C (MotC) and strongylophorine-26 (STP-26). …
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The molecular basis for tumor growth suppression by tRNA methyltransferase 9-like (TRM9L)
… research is to connect mechanistically the biochemical function of TRM9L to its tumor suppressing activity. Of my special interest is TRM9L is regulated at the protein level. In this thesis, I demonstrated that TRM9L is a phosphoprotein, with phosphorylation dynamics at serines S214, S255, …
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A Chemical-Genetic Map of Drug Resistance in Mycobacterium Tuberculosis
… a novel CRISPR interference (CRISPRi)-based chemical genetics platform. Our lab developed a CRISPRi library containing 100,000 unique knockdown strains and treated this library with a panel of some of the most important antitubercular drugs. The fitness of each mutant in the library was …
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Mechanism of transcranial focused ultrasound regulating the neuronal activity of the retrosplenial cortex
… chain reaction, immunofluorescent staining, chemical genetics, and multi-channel in vivo recording to explore whether tFUS affected neuronal activity in the pain-related brain region, retrosplenial cortex (RSC). Moreover, tFUS significantly increased paw withdrawal threshold (PWT) and …
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The Integration of Metabolite and Hormone Signalling Drives Seedling Development
… with sugars during seedling development, a chemical screen was performed in search of compounds that modify responses to sucrose. This screen identified an interaction between the folate inhibitor sulfamethoxazole (SMX) and sucrose that resulted in changes to auxin signalling and …
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Neural Circuit Dependence of Acute and Subacute Nociception in C. Elegans
… silencing the AIB interneuron with the a chemical genetics system using the histamine-gated chloride channel resulted in complete loss of nociceptive avoidance behaviors induced by slow-ramping SRG-36 receptor in ASH, but had less of an effect on SRG-34 avoidance. Selectively silencing the …
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Regulation of Toxoplasma Motility by Calcium-Dependent Protein Kinases
… cellular pathways. Using a combination of chemical and genetic approaches we demonstrated that two of the conserved CDPKs are required for motility at different stages in the <italic>T. gondii</italic> life cycle. Generating a conditional knockout, we showed that TgCDPK1 is required for …
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Dissection of spatiotemporal intracellular signaling using engineered chemical and genetic tools
… This thesis describes the development of chemical genetic tools that specifically control individual signaling nodes in a cell using three distinct approaches. The first approach utilizes conformation-selective inhibitors that modulate the allosteric regulation of Src Family Kinases …