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Elastin-Like Polypeptide As A Model To Study Intrinsically Disordered Proteins, Sadegh Majdi
Elastin-Like Polypeptide As A Model To Study Intrinsically Disordered Proteins, Sadegh Majdi
Theses and Dissertations
The elastin-like polypeptide (ELP) is a well-studied structural protein that is easily amenable to amino acid (AA) sequence modifications and has the potential to yield a wide variety of uses in bioengineering and biomedical applications. One unique property of ELP is the inclusion of intrinsically disordered domains (IDP) within the structure that allow for its diversity of physical properties. While it is generally understood that amino acid sequence dictates protein folding arrangements, the contributions of specific amino acid sequences to the intrinsic disorder of ELP has yet to be fully resolved. Therefore, identifying the contributions of specific amino acid sequences …
Investigation Into The Genetic Basis Of Capsaicin Production In Peppers Using Next Generation Rna Sequencing And Synthetic Biology Approaches, Ryan Patrick Calhoun
Investigation Into The Genetic Basis Of Capsaicin Production In Peppers Using Next Generation Rna Sequencing And Synthetic Biology Approaches, Ryan Patrick Calhoun
Theses and Dissertations
Capsaicin, a molecule synthesized by plants in the Capsicum genus, is popular for its ability to produce a sensation of burning in any tissue it encounters. The synthesis of capsaicin molecules is achieved through the capsaicin biosynthesis pathway. In this dual study, our goal was to insert two crucial genes, pun1 and pAMT, into a strain of Saccharomyces cerevisiae to allow capsaicin synthesis and perform Illumina RNA sequencing on seven pepper species of increasing pungency to identify other key or novel genes needed or related to capsaicin synthesis. We implemented a golden gate cloning strategy to insert our genes of …
Gene Expression Analysis Revealed The Activation Of Immune Responses During The Postnatal Development Of The Cerebellum In A Mouse Model Of Niemann-Pick Type C, Sierra Elizabeth Melli
Gene Expression Analysis Revealed The Activation Of Immune Responses During The Postnatal Development Of The Cerebellum In A Mouse Model Of Niemann-Pick Type C, Sierra Elizabeth Melli
Theses and Dissertations
Niemann-Pick Type C (NPC) is a recessive neurodegenerative lysosomal storage disorder that is caused by autosomal recessive mutations. The mutations result in the inactivation of NPC1 and NPC2 proteins. Inactivation of the NPC1 protein results in the accumulation of cholesterol within the endosomal and lysosomal compartments of cells including Cerebellar Purkinje cells. This accumulation of cholesterol leads to symptoms of dementia, neurodegeneration and potential of early childhood death in cases of early onset. In this study, we analyze the gene expression levels using the RNAseq technique in order to determine whether there is a significant difference between the expression of …
Identifying Inhibitors Targeting The Nonstructural Protein 15 And Main Protease Of Coronaviruses Using Molecular Docking And Molecular Dynamics Simulation, Nakoa Kristen Webber
Identifying Inhibitors Targeting The Nonstructural Protein 15 And Main Protease Of Coronaviruses Using Molecular Docking And Molecular Dynamics Simulation, Nakoa Kristen Webber
Theses and Dissertations
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020 has impacted daily life globally for over a year. While multiple vaccines have been authorized for emergency use and one oral medication has entered clinical trials, we are still seeking antiviral drugs for a long-term treatment for SARS-CoV-2 as well as other coronaviruses. Computational drug screenings of two SARS-CoV-2 protein target candidates are presented in this thesis: the nidoviral RNA uridylate-specific endoribonuclease (Nsp15) and the main protease (Mpro) of SARS-CoV-2. Nonstructural proteins of coronaviruses were selected as targets as they are more conserved across coronavirus strains than …
Development And Implementation Of A Coarse-Grained Markov State Model, Brian Chen
Development And Implementation Of A Coarse-Grained Markov State Model, Brian Chen
Theses and Dissertations
Markov State Models (MSMs) are constructed from Molecular Dynamics (MD) simulation data, high-resolution spatial and temporal information stored in the form of trajectories, of biological processes, such as ligand-receptor bonding, as a model to understand detailed kinetic information. Traditional MSM implementations involve a clustering step that clusters the MD trajectories into thousands of experimentally unverifiable clusters known as "microstates" before lumping them together into "macrostates". This work details a novel software implementation, using a combination of R, Python, and Tcl, that I have created for the purpose of creating a coarse-grained MSM that directly clusters the MD trajectories into a …
Chromatin Digestion By The Chemotherapeutic Agent Bleomycin Produces Nucleosome And Transcription Factor Footprinting Patterns Similar To Micrococcal Nuclease, Joshua Michael Stolz
Chromatin Digestion By The Chemotherapeutic Agent Bleomycin Produces Nucleosome And Transcription Factor Footprinting Patterns Similar To Micrococcal Nuclease, Joshua Michael Stolz
Theses and Dissertations
Bleomycin (BLM), a glycopeptide antibiotic commonly used in chemotherapeutic treatments, has been shown to produce single and double stranded DNA breaks. Subsequent analysis of DNA fragmentation patterns has demonstrated preferential digestion of chromatin in the TSS of active genes and the ability to produce nucleosome-sized fragments within intact chromatin. Nucleosome positioning plays a critical role in the regulation of gene activation. Currently, micrococcal nuclease (MNase) is used as the standard for mapping the position of nucleosomes in the genome. In order to identify whether BLM can be used as an effective nucleosome-mapping agent, BLM was used to digest chromatin in …
An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese
An In Silico Study Of G Protein-Coupled-Receptor Activation, Specifically In The Corticotropin Releasing Factor Receptor And The Glucagon-Like Peptide Receptor, Nicolas Angelo Scorese
Theses and Dissertations
The drug discovery process is an extremely long and expensive process that modern computational methods help to alleviate. Through the use of computational methods, we provide information and insight into the activation methods of class B GPCRs so that future drugs can be developed to have less side effects. The first study focuses on the corticotropin releasing factor receptor, which is a good drug target for anxiety and depression. A mechanism of activation was theorized which focuses less on molecular switches (as has been the focus of several papers) and more on large scale conformation at the intracellular region of …
Monitoring Expression Of Metabolic Genes During The Hypoxic Response Of S. Cerevisae, Nikkoli Lueder
Monitoring Expression Of Metabolic Genes During The Hypoxic Response Of S. Cerevisae, Nikkoli Lueder
Theses and Dissertations
All organisms appear to have the ability to sense and respond to changes in their environment. Hypoxia, or low oxygen, is experienced by many organisms at some point in their life cycle. Some organisms such as S. cerevisiae, a species of yeast, respond by dramatically altering gene expression. The result is that genes needed in the new environment are turned on and unneeded genes are turned off. S. cerevisiae has been used in our study because it shares many genes with other eukaryotes, including humans, so many of our findings are applicable to these organisms. Here, we tried to understand …
A Mechanical Study Of Cancer Drug-Receptor Interactions, Specifically In G-Quadruplex Dna And Topoisomerase I Enzymes, Kelly Ann Mulholland
A Mechanical Study Of Cancer Drug-Receptor Interactions, Specifically In G-Quadruplex Dna And Topoisomerase I Enzymes, Kelly Ann Mulholland
Theses and Dissertations
Computational methods are becoming essential in drug discovery as they provide information that traditional drug development methods lack. Using these methods to understand drug-receptor interactions in detail, researchers are able to efficiently design promising drug candidates. In this study, extra precision Glide docking, molecular dynamics simulations and MMGBSA binding energy calculations provided information about the binding behavior of small molecules to two specific targets for current cancer therapeutics: G-quadruplex DNA and Topoisomerase I enzyme. The first study focuses on the compound Telomestatin, which induces apoptosis of various cancer cells with a relatively low effect on somatic cells due to its …
Examining The Evolutionary Constraints Of Gene Expression Levels In S. Cerevisiae, Andrea Janelle Jackson
Examining The Evolutionary Constraints Of Gene Expression Levels In S. Cerevisiae, Andrea Janelle Jackson
Theses and Dissertations
It has been widely reported that some genes are expressed at a higher level than others. However, it has not been shown whether each gene is expressed consistently between studies and at the same level compared to all other genes. Here, we examined six RNA-seq datasets and found that the mRNA level of each gene is indeed consistent relative to all other genes. This result implies that there are evolutionary pressures that drive genes to maintain either low or high expression. In order to identify these pressures, we compared gene expression level to the features of each gene (or associated …