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 18 of 18 for “"Deep Mutational Scanning"”.
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Conformational engineering of human chemokine receptors and HIV-1 Env using deep mutational scanning
… However, by combining directed evolution and deep sequencing with site- saturation mutagenesis (SSM) to create unbiased, diverse libraries, it is now possible to track the phenotypic fitness of thousands of sequence variants in a single experiment. This is known as deep mutational scanning, …
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Probing PAX6-DNA interactions using high-throughput yeast one-hybrid assays and deep mutational scanning
… I used a combination of yeast one-hybrid and deep mutational scanning in competitive growth assays to probe the functional consequences of almost all the possible single amino acid variants in the paired domain of PAX6. The results showcase the capabilities of the assay to reproducibly …
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Synthetic Transcription Factor Allostery Mapping and Analysis
… engineered LacI-based anti-repressors. Through deep mutational scanning, we have generated comprehensive datasets correlating single-mutant genotypes with functional phenotypes. Building upon the experimental dataset and alongside ongoing machine learning efforts that utilize it, I introduce a …
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Modelling the structural, functional and phenotypic consequences of protein coding mutations
… biology, and protein variants are no exception. Deep mutational scanning experiments exhaustively measure the fitness of variants in a protein, which gives us more experimentally validated mutational consequence measurements than ever before. Such advances, together with ever larger sequence and …
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Modeling the effects of site-specific amino-acid preferences on protein evolution.
… two existing methods, phylogenetics and deep mutational scanning, to understand the effect of site-specific amino-acid constraint on protein evolution. These two methods, one computational and one experimental, have complementary strengths and weaknesses. Phylogenetics provides methods to …
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Characterising fitness landscapes of protein evolution by next-generation sequencing
… two experimental assays (GFP, PTE) for deep mutational scanning and a new software toolkit, InDelScanner, for interpreting resulting data that contain InDels. With GFP, I sorted the deletions and substitution libraries into three activity fractions using FACS, then deep sequenced them …
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Hierarchy of Interactions in Protein Evolution
… of co-evolution. Here, we use an extension of deep mutational scanning to analyze nearly 50,000 single and double mutations in several homologs of a model protein - the PDZ family of protein interaction domains. Across the domains queried experimentally, the distributions of couplings between …
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Integrative approaches to decipher influenza evolution, antibody responses, and AI-driven specificity prediction
… through three interconnected research areas: (1) deep mutational scanning (DMS) to map sequence–function relationships in influenza viral proteins; (2) large-scale analysis of antibody responses to SARS-CoV-2 and influenza; and (3) development of AI models to predict antibody specificity. Chapter …
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Serotonin transporter import
… mutagenesis studies, none so expansive as our deep mutational scans, where we have characterized the effects of every point mutant on the function and surface localization of two of these proteins, the serotonin transporter (SERT) and the dopamine transporter (DAT). Collaborating with Diwakar …
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The genetic landscape of protein-protein interaction specificity
… systems as a model, we use a variant of deep mutational scanning to dissect the positive and negative contributions of antitoxin residues that dictate toxin specificity. By screening a combinatorially complete library of antitoxin variants, we uncover a distribution of fitness effects for …
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Defining the Influence of Host Cell Proteostasis Networks and Temperature on Influenza Evolution
… temperature of the cell. My first project uses deep mutational scanning to elucidate the roles of the host proteostasis networks in defining influenza hemagglutinin’s evolutionary ability. My second project takes a similar approach to investigate how high or low temperature impact the accessible …
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The Structural Distribution of Epistasis in a Pair of Essential Metabolic Enzymes
… in unexpected ways. This context-dependence of mutational effects is epistasis. Extensive progress has been made in our ability to identify epistasis between proteins. However, how the epistasis between a pair of proteins is distributed across the amino acid sequence is less clear. Previous work …
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Leveraging HSF1 chemical-genetic tools to elucidate mechanisms of proteostasis
… during initial proteotoxic stress. Next, I used deep-mutational scanning to identify HSF1 as a critical non-oncogenic component capable of tuning fitness of dominant-negative mutations within the oncogene tumor protein 53 (TP53). Within the context of basal temperatures, the impact of HSF1 …
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Chaperoning viral protein evolution
… systematic quantification of influenza protein mutational tolerance upon perturbation of host proteostasis, for which I applied deep mutational scanning to comprehensively profile the mutational tolerance of influenza nucleoprotein and hemagglutinin in modulated cytosolic and endoplasmic …
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Soluble decoy receptors for broad neutralization of viruses and their variants
Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2025-08-01
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Rationalising and accelerating enzyme engineering by quantitative sequence-function profiling in microdroplets
… sequence function mapping workflow, long-read deep mutational scanning (lrDMS), which allows us to screen the combinatorial effects of tens of thousands of mutations within two weeks, a scale, speed, and cost not feasible with robotic plate screening workflows. By obtaining mutagenic profiles …
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Replaying Life's Tape With Intraclonal Germinal Center Evolution
… binding and expression of clone 2.1 through deep mutational scanning (DMS) and cryo-electron microscopy (CryoEM). DMS elucidated that chIgY B cells must avoid ~13 deleterious mutations in order to make one affinityincreasing mutations. CryoEM revealed that central paratope of clone 2.1 is …
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Unsupervised inference models for structural and functional properties of protein sequences
L'abstract è presente nell'allegato / the abstract is in the attachment