Structural Biology Commons^™

The Effect Of Alkalinity On Lampricide Effectiveness And Gill Physiology In Invasive Sea Lamprey (Petromyzon Marinus), Alexandre J. Walsh

Theses and Dissertations (Comprehensive)

The pesticides, 3-trifluoromethyl-4-nitrophenol (TFM) and niclosamide are used to control populations of invasive sea lamprey (Petromyzon marinus) in the Laurentian Great Lakes of North America. Added to streams infested with larval sea lamprey, the effectiveness of these pesticides, commonly called lampricides, are strongly influenced by water pH, with greater toxicity for both TFM and niclosamide in lower pH than higher pH water. However, the TFM and niclosamide sensitivity of sea lamprey are also greater in poorly buffered, low alkalinity water than in high alkalinity water but it is unclear why. One goal of my thesis was to propose …

Characterization Of Cl-Par-4: Wt Vs. Mutant, Samjhana Pandey, Krishna K. Raut, Andrea M. Clark, Antoine Baudin, Lamya Djemri, David S. Libich, Steven M. Pascal

The Graduate School Posters

Intrinsically disordered proteins (IDPs) play important roles in regulation of cell signaling pathways as well as cellular processes. Dysregulation of these proteins is associated with several human diseases. Prostate apoptosis response-4 (Par-4), a proapoptotic tumor suppressor protein, is categorized as an intrinsically disordered protein and downregulation of this protein has been reported in myriad of cancers including glioma, breast cancers, and prostate cancers. The caspase-cleaved fragment of Par-4 (cl-Par-4) plays an active role in tumor suppression by inhibiting several cell survival pathways.

Here, we employed site-directed mutagenesis to introduce a point mutation in the cl-Par-4 wildtype (WT) to generate the …

Par-4: An Attractive Target For Cancer Therapy, Krishna K. Raut, Antoine Baudin, David S. Libich, Lijun Liu, Scott Lovell, Steven M. Pascal

College of Sciences Posters

Lack of early diagnosis, cancer recurrence, metastasis, and adverse side effects are some of the major problems in the treatment of cancers. Par-4, a tumor suppressor protein, is an attractive target for cancer therapy as it selectively kills cancer cells. Cl-Par-4 is the active fragment of Par-4 that enters the nucleus and selectively induces apoptosis in cancer cells. It has also been reported that Par-4 increases the susceptibility of cancer cells to chemotherapy and reverses cancer recurrence. Further, Par-4 has been shown to play a dual role: inhibition of EMT (Epithelial-mesenchymal transition) as well as assistance in the reverse process, …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

A Pipeline To Generate Deep Learning Surrogates Of Genome-Scale Metabolic Models, Achilles Rasquinha

Computer Science and Engineering: Theses, Dissertations, and Student Research

Genome-Scale Metabolic Models (GEMMs) are powerful reconstructions of biological systems that help metabolic engineers understand and predict growth conditions subjected to various environmental factors around the cellular metabolism of an organism in observation, purely in silico. Applications of metabolic engineering range from perturbation analysis and drug-target discovery to predicting growth rates of biotechnologically important metabolites and reaction objectives within dierent single-cell and multi-cellular organism types. GEMMs use mathematical frameworks for quantitative estimations of flux distributions within metabolic networks. The reasons behind why an organism activates, stuns, or fluctuates between alternative pathways for growth and survival, however, remain relatively unknown. GEMMs …

Potential Use Of Proteolytic Bacteria Paenibacillus Dendritiformis (Bt7) Isolated From Batu Tannery Effluents For The Detergent Industry, Chandran Masi, Degafneh Tadesse, Abate Ayele

Karbala International Journal of Modern Science

This research was aimed at identifying a bacterium that can produce alkaline proteases. As a result, bacteria that produce proteases were isolated from Batu tannery effluents, tested for protease synthesis on skim milk agar plates, and validated with a protease assay. Microscopic and molecular phylogenetic analyses identified Paenibacillus dendritiformis (BT7) as the bacterial isolate with the highest alkaline protease production. The isolate's maximum enzyme production was obtained by 2% inoculum size, 40°C temperature, 9.0 pH, and a 48-hour incubation time with production media components such as glucose, casein, MgCl2, and 2% NaCl. The maximal enzyme activity was 270 U/mL under …

Examination Of The Time Delayed Induction Between Prior Encapsulation Of Catalytic Enzymes In P22 Virus-Like Particles, Andrea Hernandez Irias

Chemistry Theses

Protein cages found in nature have the ability to protect and develop new nanomaterials in order to enhance catalytic reactions. This is due to the ability of these organelle structures to mimic protein-based organelles such as Virus-Like Particles (VLPs). VLPs have the ability to not only resemble virus protein structures but to encapsulate enzymes while retaining their activity. This research examines the in vitro encapsulation withing the bacteriophage P22 derived VLP, and show that some enzymes may require a delay in encapsulation to allowed proper folding

and maturation before they can be encapsulated inside P22 as fully active enzymes. Exploring …

Visualizing Muscle Assembly And Function In C. Elegans, Michael B. Russell

Theses and Dissertations

Myofibrils produce the forces that shorten muscles during contraction and are composed of proteins arranged in repeating contractile units (sarcomeres). These are composed of various proteins that self-organize into precise, alternating groups. The process of myofibril assembly is robust, flexible, and medically relevant. Various protein isoforms have evolved to modify the assembly process and generate a variety of muscle types with distinct physiologies and dynamics. To study myofibril assembly, I used the nematode Caenorhabditis elegans (C. elegans) which is an ideal model organism for this because it is transparent and has a variety of different muscle types that are responsible …

Applications Of Nuclear Magnetic Resonance Spectroscopy: From Drug Discovery To Protein Structure And Dynamics., Mark Vincent C. Dela Cerna

Electronic Theses and Dissertations

The versatility of nuclear magnetic resonance (NMR) spectroscopy is apparent when presented with diverse applications to which it can contribute. Here, NMR is used i) as a screening/ validation tool for a drug discovery program targeting the Phosphatase of Regenerating Liver 3 (PRL3), ii) to characterize the conformational heterogeneity of p53 regulator, Murine Double Minute X (MDMX), and iii) to characterize the solution dynamics of guanosine monophosphate kinase (GMPK). Mounting evidence suggesting roles for PRL3 in oncogenesis and metastasis has catapulted it into prominence as a cancer drug target. Yet, despite significant efforts, there are no PRL3 small molecule inhibitors …

Modeling Electrostatics In Molecular Biology And Its Relevance With Molecular Mechanisms Of Diseases, Mahesh Koirala

All Dissertations

Electrostatics plays an essential role in molecular biology. Modeling electrostatics in molecular biology is complicated due to the water phase, mobile ions, and irregularly shaped inhomogeneous biological macromolecules. This dissertation presents the popular DelPhi package that solves PBE and delivers the electrostatic potential distribution of biomolecules. We used the newly developed DelPhiForce steered Molecular Dynamics (DFMD) approach to model the binding of barstar to barnase and demonstrated that the first-principles method could also model the binding. This dissertation also reflects the use of existing computational approaches to model the effects of Single Amino Acid Variations (SAVs) to reveal molecular mechanisms …

Location And Conformation Of Titin In Caenorhabditis Elegans Muscle, Gaberielle S. Prince

Theses and Dissertations

Striated muscles consist of contractile myofibrils that generate force. The repeating units (sarcomeres) of striated myofibrils contain thin & thick filaments composed of actin and myosin. In vertebrates, titin connects thin & thick filaments during myofibril assembly and produces passive tension. Invertebrate homologs of vertebrate titin are similar in structure molecularly. However, invertebrate titin homologs are smaller than vertebrate titin, and likely function differently within invertebrate muscles. Here, I used Ce-TTN-1, a titin homolog in the invertebrate roundworm C elegans. To visualize Ce-TTN-1 in C. elegans, I used Nested CRISPR gene editing to generate translational fusions of a red fluorescent …

Cdc6 Is Sequentially Regulated By Pp2a-Cdc55, Cdc14, And Sic1 For Origin Licensing In S. Cerevisiae, Jasmin Philip

Dissertations, Theses, and Capstone Projects

Control of DNA replication is critical for progression of the cell cycle and genomic stability. Cyclin-dependent kinases (CDKs) coordinate numerous phosphorylation events to accomplish two biological tasks for all living organisms: DNA replication and cell division. One CDK, Cyclin-Cdc28, is responsible for cell cycle progression in budding yeast. DNA replication requires a stepwise assembly of the pre-replicative complex on DNA, including Orc1-6, Cdc6, Cdt1 and Mcm2-7, during M-G1 phase. Cdc6 contains eight Cdc28 consensus sites, SP or TP motifs. Clb5-Cdc28 phosphorylates Cdc6-T7 to recruit Cks1, the Cdc28 phospho-adaptor, for subsequent multisite phosphorylation during S phase. There are two phospho-degrons at …

A New Insight Into Fungal Cell Wall Architecture By Functional Genomics And Solid-State Nmr Along With Recent Advancements In Dynamic Nuclear Polarization For Analyzing Biomolecules, Arnab Chakraborty

LSU Master's Theses

This dissertation summarizes the findings related to the way by which supramolecular architecture of fungal cell wall changes with genetic mutation, dispensing genes responsible for biosynthesis of cell wall polysaccharides. This is necessary because without perfect picture of how supramolecular assembly changes with genetic mutation it is hard to assess new anti-fungal targets. Alongside this we have highlighted how recent advancement into Dynamic Nuclear Polarization (DNP) methods improved characterization of biomolecules both in case of labeled and unlabeled samples.

First study utilized Solid-state NMR (SSNMR) which is a non-destructive technique hence enabled us for the first time to deduce how …

Inferring Dynamics Of Biological Systems, Tracey G. Oellerich

Biology and Medicine Through Mathematics Conference

No abstract provided.

The Effects Of Hybridization On Skeletal Morphology In Two Closely Related Populations Of Rhesus Macaques (Macaca Mulatta): A Geometric Morphometric Approach, Cody Zachery Schumacher

Theses and Dissertations

Precise identification and classification techniques are vital for the field of paleoanthropology to ensure that hominin fossilized remains are labeled accurately. The morphology of extinct hominin specimens will typically be compared to extant nonhuman primate species because of how closely related they are phylogenetically. Observable similarities in their morphological variation can be examined to infer which traits may be a result of evolution and this can update our understanding of their evolutionary relationships. The genus Macaca displays a level of morphological variation that is similar to that seen in the genus Homo, therefore macaques can be used as an analogous …

Supertertiary Structural Dynamics Modulate Function In Postsynaptic Density Protein 95, George L. Hamilton Iii

All Dissertations

Proteins, RNA, and DNA serve as the primary sub-cellular machinery that give rise to the necessary functions of life. The long-standing paradigm has been that the structures of biomolecules, or the arrangement of the subunits that make up a biomolecule, determine biological function. However, biomolecules are not static objects. Instead, they often undergo structural rearrangements that are crucial to enabling and regulating their functions. In my thesis I present several studies of the interplay between the structures, dynamics, and functions of biomolecules that combine experimental fluorescence spectroscopy and computational methods to probe these systems at the single-molecule level. In particular, …

Modulation Of Kras Structure And Dynamics By Kras Ubiquitination And Membrane Depolarization, Vinay Nair

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

KRAS, a 21 kDa small GTPase protein, functions as a molecular switch playing a key role in regulating cell proliferation. Dysregulation of KRAS signaling by oncogenic mutations leads to uncontrolled cell proliferation, a hallmark of cancer cells. Attempts to therapeutically target oncogenic KRAS have led to limited success resulting in a need to identify new mechanisms to targeting KRAS. The interaction of KRAS with its regulators, effectors, and the membrane present one such avenue. In this study, we investigated how post-translational covalent and environmental modifications could modulate these interactions of KRAS. Using computational molecular dynamics simulations, nuclear magnetic resonance spectroscopy …

Computational Investigations Into Binding Dynamics Of Tau Protein Antibodies: Using Machine Learning And Biophysical Models To Build A Better Reality, Katherine Lee

University Scholar Projects

Misregulation of post-translational modifications of microtubule-associated protein tau is implicated in several neurodegenerative diseases including Alzheimer’s disease. Hyperphosphorylation of tau promotes aggregation of tau monomers into filaments which are common in tau-associated pathologies. Therefore, tau is a promising target for therapeutics and diagnostics. Recently, high-affinity, high-specificity single-chain variable fragment (scFv) antibodies against pThr-231 tau were generated and the most promising variant (scFv 3.24) displayed 20-fold increased binding affinity to pThr-231 tau compared to the wild-type. The scFv 3.24 variant contained five point mutations, and intriguingly none were in the tau binding site. The increased affinity was hypothesized to occur due …

Design, Synthesis, And Analysis Of Paired Coiled-Coil Peptidic Molecular Building Blocks Used For Linearly Controlled Self-Assembly Of Α-Helical Coiled-Coil Heterodimer Peptide Pairs, Jason Distefano

Chemistry Theses

Molecular building blocks are fundamental to biological synthesis and processes and have been utilized in advanced materials, drugs and drug delivery systems, and biotechnology. Proteins have been used as molecular building blocks for the construction of complex, well-ordered structures. Coiled-coil protein domains are essential subunits used for the oligomerization of protein complexes, gene expression, and structural elements of biological materials. The synthesis and assembly of proteins utilizing coiled-coil motifs are of great scientific interest due to their potential applications in disease treatment, biomechanical motors, nanoscale delivery systems, etc. However, assembling protein complexes with specific morphology is still challenging because …

Foldamers Reveal And Validate Therapeutic Targets Associated With Toxic Α-Synuclein Self-Assembly, Jemil Ahmed, Tessa C. Fitch, Courtney M. Donnelly, Johnson A. Joseph, Tyler D. Ball, Mikaela M. Bassil, Ahyun Son, Chen Zhang, Aurélie Ledreux, Scott Horowitz, Yan Qin, Daniel Paredes, Sunil Kumar

Chemistry and Biochemistry: Faculty Scholarship

Parkinson’s disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation. However, the bottleneck towards achieving this goal is the identification of αS domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified αS sequences-based targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays …