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Articles 181 - 210 of 286
Full-Text Articles in Biochemistry
Functional Connectivity Of Red Chlorophylls In Cyanobacterial Photosystem I Revealed By Fluence-Dependent Transient Absorption, Sara Sohail, S. Sohoni, P.-C. Ting, L. R. Fantz, S. M. Abdulhadi, C. Macgregor-Chatwin, A. Hitchcock, C. N. Hunter, G. S. Engel, S. C. Massey
Functional Connectivity Of Red Chlorophylls In Cyanobacterial Photosystem I Revealed By Fluence-Dependent Transient Absorption, Sara Sohail, S. Sohoni, P.-C. Ting, L. R. Fantz, S. M. Abdulhadi, C. Macgregor-Chatwin, A. Hitchcock, C. N. Hunter, G. S. Engel, S. C. Massey
Chemistry & Biochemistry Faculty Works
External stressors modulate the oligomerization state of photosystem I (PSI) in cyanobacteria. The number of red chlorophylls (Chls), pigments lower in energy than the P₇₀₀ reaction center, depends on the oligomerization state of PSI. Here, we use ultrafast transient absorption spectroscopy to interrogate the effective connectivity of the red Chls in excitonic energy pathways in trimeric PSI in native thylakoid membranes of the model cyanobacterium Synechocystis sp. PCC 6803, including emergent dynamics, as red Chls increase in number and proximity. Fluence-dependent dynamics indicate singlet–singlet annihilation within energetically connected red Chl sites in the PSI antenna but not within bulk Chl …
Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy
Induced Mutagenesis In West Nile Virus Non-Structural Protein 3 With A Discussion Of The Mutation's Effects On Viral Properties, Caden Connealy
Honors Program: Senior Projects (Public)
West Nile Virus (WNV), a member of the Flaviviridae family and introduced to the Western hemisphere in 1999, presents a unique and emerging threat to human health. Infection in humans is often mild but can occasionally result in severe neurological impairment and even death. West Nile Virus non-structural protein 3 (NS3) plays an important role in the process of viral genome amplification. More specifically, the C-terminal domain of the protein folds into a helicase enzyme, which is responsible for the “unwinding” of double-stranded RNA intermediates and RNA secondary structure on the WNV genome. This is a vitally important step in …
Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman
Domain Communication In Bifunctional Proline Utilization A From Sinorhizobium Meliloti, Emma Bitterman
Honors Program: Senior Projects (Public)
The reduction potential of flavin bound to Sinorhizobium meliloti proline utilization A (SmPutA) is beneficial in providing vital information on enzyme activity and the active site environment. Flavin is crucial in biological metabolism such as aerobic respiration and other important processes like oxygen activation that are catalyzed by flavin-dependent enzymes. (4). In this study, we seek to determine whether the redox potential of SmPutA-bound flavin can be used to characterize potential long-distance communication and analyze the possibilities of inactivation reversibility. SmPutA is a large bifunctional enzyme that catalyzes the overall oxidation of proline to glutamate via two catalytic domains (1). …
Development, Optimization, And Validation Of A High-Sensitivity Capillary Zone Electrophoresis System For Bioanalytical Applications, Aaron I. Mena
Development, Optimization, And Validation Of A High-Sensitivity Capillary Zone Electrophoresis System For Bioanalytical Applications, Aaron I. Mena
Electronic Theses and Dissertations
Capillary zone electrophoresis (CZE) is a powerful analytical technique widely used for biomolecular separation due to its high resolution, efficiency, and sensitivity. This report presents the development and validation of a novel CZE system designed to improve modularity, reproducibility, and operational efficiency. The system integrates a laser-induced fluorescence (LIF) detection method with a 488 nm laser, enhanced fluid control through a negative pressure system, and a user-friendly GUI for automated operation and data acquisition. Performance verification included pressure stability tests, fluorescence accuracy assessments, and electrophoretic reproducibility studies. Comparative analysis with a previous CZE iteration confirmed improved baseline stability, peak resolution, …
Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman
Synthetic Protein Mimetic Based Therapies For Neurodegeneration, Nicholas H. Stillman
Electronic Theses and Dissertations
Protein-protein interactions (PPIs) are crucial for the regulation of a majority of, if not every fundamental cellular process. Despite their role in regular biological processes, dysregulated and/or aberrant protein-protein interactions (aPPIs) are often related to the onset of disease including cancer, viral infection, and amyloid diseases. aPPIs have historically been deemed ‘undruggable’ due to their large surface area and lack of a binding cavity; however, today, more than 40 disease-related aPPIs have been targeted with small molecules and several of those have reached clinical trials.
A class of synthetic protein mimetics called oligopyridylamides (OPs) has been shown to inhibit disease-related …
The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner
The Guanine Nucleotide Exchange Factor Ric-8a Regulates The Sensitivity Of Constitutively Active Gαq To The Inhibitor Ym-254890, Morgan Dwyer, Jiansong Luo, Tyson Todd, Kendall Blumer, Gregory Tall, Philip Wedegaertner
Department of Biochemistry and Molecular Biology Faculty Papers
Heterotrimeric G proteins are stimulated under normal circumstances by G protein-coupled receptors to promote downstream intracellular signaling. Mutations can occur in αq at glutamine 209 (Q209) that cause constitutive, G protein-coupled receptor independent signaling due to disruption of GTPase activity. Specifically, Q209L/P mutations are oncogenic drivers of uveal melanoma. YM-254890 (YM) has been shown to selectively inhibit both WT and constitutively active (CA) αqQ209L/P by preventing the release of GDP and exchange for GTP, thereby halting downstream signaling. Because αqQL/P are thought to be primarily GTP-bound and GTPase deficient, the current mechanistic understanding of YM inhibition needs further investigation to …
Synthesis Of A Series Of Rare-Earth-Based Multi-Anion Chalcogenide Iodides Re3Si2SeXS8-XI (Re = La, Ce, Pr, And Nd) Using The Flux-Assisted Boron-Chalcogen Mixture Method, Gopabandhu Panigrahi, Habiba Binte Kashem, Gregory Morrison, Hans Conrad Zur Loye
Synthesis Of A Series Of Rare-Earth-Based Multi-Anion Chalcogenide Iodides Re3Si2SeXS8-XI (Re = La, Ce, Pr, And Nd) Using The Flux-Assisted Boron-Chalcogen Mixture Method, Gopabandhu Panigrahi, Habiba Binte Kashem, Gregory Morrison, Hans Conrad Zur Loye
Faculty Publications
Single crystals and polycrystalline powders of rare earth mixed chalcogenide iodides La3Si2Se1.21S6.79I, Ce3Si2Se1.39S6.61I, Pr3Si2Se1.22S6.78I, and Nd3Si2Se1.18S6.82I were prepared using the reactive flux-assisted boron-chalcogen mixture (BCM) method at 850 °C. All compounds crystallized in the monoclinic crystal system, space group C2/c (space group number 15). The series adopts the La3Si2O8Cl structure type, containing isolated SiQ4 tetrahedra connected by REQ8 (RE = La, Ce, Pr and Nd) polyhedra; this arrangement creates tunnels that are filled by I atoms. The partial substitution of S by Se was carried out to modulate the optical properties. Phase pure samples and uniform solid solutions were obtained …
The Expression Profile Of The Rank/Rankl/Opg Pathway In Breast Cancer Stem Cells Isolated From Breast Cancer Cell Lines, Mohamed M. Kamal, Hassnaa H. Elgohary, Sherine Maher Rizk, Nadine H. Maurice
The Expression Profile Of The Rank/Rankl/Opg Pathway In Breast Cancer Stem Cells Isolated From Breast Cancer Cell Lines, Mohamed M. Kamal, Hassnaa H. Elgohary, Sherine Maher Rizk, Nadine H. Maurice
Pharmacy
The RANK/RANKL/OPG signaling pathway plays a crucial role in breast cancer progression and metastasis. However, its expression patterns and potential implications in breast cancer stem cells remain poorly understood. This study aimed to characterize the expression profile of this pathway in breast cancer stem cells isolated from two distinct breast cancer cell lines: MDA‐MB‐231 and MCF‐7. Mammospheres (MS), representing breast cancer stem cells, were generated using agar‐coated 6 well tissue culture plates in suitable mammospheres culture conditions. Flow cytometric analysis showed enrichment of the CD44+/ CD24− subpopulations in the mammospheres cultures, with MDA‐MB‐231 exhibiting a higher percentage compared to MCF‐7. …
Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov
Structural Basis For Intrinsic Strand Displacement Activity Of Mitochondrial Dna Polymerase, Ashok Nayak, Viktoriia Sokolova, Sirelin Sillamaa, Karl Herbine, Juhan Sedman, Dmitry Temiakov
Department of Biochemistry and Molecular Biology Faculty Papers
Members of the Pol A family of DNA polymerases, found across all domains of life, utilize various strategies for DNA strand separation during replication. In higher eukaryotes, mitochondrial DNA polymerase γ relies on the replicative helicase TWINKLE, whereas the yeast ortholog, Mip1, can unwind DNA independently. Using Mip1 as a model, we present a series of high-resolution cryo-EM structures that capture the process of DNA strand displacement. Our data reveal previously unidentified structural elements that facilitate the unwinding of the downstream DNA duplex. Yeast cells harboring Mip1 variants defective in strand displacement exhibit impaired oxidative phosphorylation and loss of mtDNA, …
Molecular Interaction Of Purple Rice Ferulic Acid And Skin Aging-Related Enzymes, Ernanin Dyah Wijayanti, Fatchiyah Fatchiyah, Anna Safitri, Dian Siswanto
Molecular Interaction Of Purple Rice Ferulic Acid And Skin Aging-Related Enzymes, Ernanin Dyah Wijayanti, Fatchiyah Fatchiyah, Anna Safitri, Dian Siswanto
Makara Journal of Science
Purple rice is rich in ferulic acid, a phenolic acid abundant in rice. Ferulic acid (FA) has long been recognized for its anti-oxidant properties, which are linked to its skin anti-aging activity owing to its ability to scavenge free radicals and pro-tect cells from damage. Skin anti-aging activity could be assessed by inhibiting skin aging enzymes. However, there was limited information on the mechanism of FA inhibition of these enzymes. This study focused on the molecular interac-tion between purple rice FA and collagenase or tyrosinase, both with and without their substrates. The interaction be-tween FA (CID 445858), collagenase (2Y6I), tyrosinase …
Biochemical, Structural, And Conformational Characterization Of A Fungal Ethylene-Forming Enzyme, Shramana Chatterjee, Joel A. Rankin, Mark A. Farrugia, Simahudeen Bathir J S Rifayee, Christo Z. Christov, Jian Hu, Et. Al.
Biochemical, Structural, And Conformational Characterization Of A Fungal Ethylene-Forming Enzyme, Shramana Chatterjee, Joel A. Rankin, Mark A. Farrugia, Simahudeen Bathir J S Rifayee, Christo Z. Christov, Jian Hu, Et. Al.
Michigan Tech Publications
The ethylene-forming enzyme (EFE) from the fungus Penicillium digitatum strain Pd1 was heterologously produced in Escherichia coli and its properties were compared to the extensively characterized bacterial enzyme from Pseudomonas savastanoi strain PK2. Both enzymes catalyze four reactions: the conversion of 2-oxoglutarate (2OG) to ethylene and CO2, oxidative decarboxylation of 2OG coupled to L-arginine (L-Arg) hydroxylation, uncoupled oxidative decarboxylation of 2OG, and the production of 3-hydroxypropionate (3-HP) from 2OG. The strain Pd1 enzyme exhibited a greater ratio of ethylene production over L-Arg hydroxylation than the PK2 strain EFE. The uncoupled decarboxylation of 2OG and …
Mechanisms Of Macrophage Metabolic Activation And Paracrine Wnt Signaling In The Pathogenesis Of Systemic Sclerosis, Emily Ann Morris
Mechanisms Of Macrophage Metabolic Activation And Paracrine Wnt Signaling In The Pathogenesis Of Systemic Sclerosis, Emily Ann Morris
Dartmouth College Ph.D Dissertations
Systemic sclerosis (SSc) is a chronic autoimmune disease of unknown etiology. We have previously shown that macrophages (MØs) play a critical role in its pathogenesis; however, the mechanisms driving MØ activation in SSc remain poorly understood. This dissertation investigates the molecular signaling pathways and biochemical mechanisms underlying profibrotic MØ activity in SSc.
First, I identify a novel MØ-specific effect of mycophenolate mofetil (MMF), the standard-of-care treatment for SSc. While MMF is a well characterized lymphostatic, my findings demonstrate that its active metabolite, mycophenolic acid (MPA), is also capable of directly inhibiting myeloid viability and profibrotic MØ activation by suppressing de …
First-In-Class Peptide Molecules Targeting The Mien1 Cancer Signaling Pathway, For Which No Inhibitors Have Been Identified To Date., Amit Tripathi, Jamboor K. Vishwanatha
First-In-Class Peptide Molecules Targeting The Mien1 Cancer Signaling Pathway, For Which No Inhibitors Have Been Identified To Date., Amit Tripathi, Jamboor K. Vishwanatha
Research Symposium
Background: Migration and Invasion Enhancer 1 (MIEN1) is a critical oncogene that drives cancer cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in various cancers. MIEN1 overexpression is linked to aggressive tumor progression and poor prognosis. Despite its established role in cancer biology, targeted therapeutic options remain unexplored. This study aimed to identify and characterize first-in-class therapeutic molecules targeting the MIEN1 signaling pathway to inhibit cancer progression.
Methods: To develop novel bio-active peptides, we leveraged conserved immunoreceptor tyrosine-based activation motif (ITAM) and prenylation motifs within the MIEN1 protein sequence. Using rational peptide design, we identified and synthesized bioactive peptides, namely LA3IK …
Nanostructure Retention To 1100 °C In Soft-Templated Niobium Tungstates Using Dual-Carbon Strategy, Sean C. Wechsler, Alexander Gregg, Coby S. Collins, Santosh Kiran Balijepalli, Morgan Stefik
Nanostructure Retention To 1100 °C In Soft-Templated Niobium Tungstates Using Dual-Carbon Strategy, Sean C. Wechsler, Alexander Gregg, Coby S. Collins, Santosh Kiran Balijepalli, Morgan Stefik
Faculty Publications
Mesoporous metal oxides (MMOs) have diverse applications including energy storage, catalysis, and separation membranes. Block polymer structure directing agents enable the control of morphology and pore size, however preservation of the nanostructure is often limited to a narrow range of heat treatment temperatures which constrains the tailoring of defect chemistries. High temperature treatments typically lead to collapse of the porous structure as surface area is reduced during crystal growth. Here, using a mesoporous niobium tungstate it is shown that neither in situ carbon generation nor ex situ carbon infiltration alone enable preservation of the ordered mesostructure at temperatures high enough …
Cryptosporidium Virus Integration Into The Host Cells, Alyssa Genaro
Cryptosporidium Virus Integration Into The Host Cells, Alyssa Genaro
Biochemistry and Molecular Biology
Cryptosporidiosis is a disease that affects a large amount of people and having a high mortality rate for those that are immunocompromised such as the elderly and infants. The disease is linked to a parasite called Cryptosporidium parvum, which is mostly known to infect cattle and other mammals such as mice and humans. The parasite contains a double stranded RNA virus, the Cryspovirus (CSpV1) that has a non-enveloped icosahedral capsid, with a T=2* icosahedral symmetry. Little is known is known about the contribution of CSpV1 to the disease; In this study we show that infection of an immunocompromised mouse model …
Assessment Of Physiological & Biochemical Changes In Tomato Plants Treated With Plant Growth Promoting Rhizobacteria (Pgpr) Under Salinity Stress Conditions, Mohammed Sharif Alhosani
Assessment Of Physiological & Biochemical Changes In Tomato Plants Treated With Plant Growth Promoting Rhizobacteria (Pgpr) Under Salinity Stress Conditions, Mohammed Sharif Alhosani
Theses
Plant growth-promoting rhizobacteria (PGPRs) can effectively mitigate the negative impacts of salt stress on plants. The present study reports the isolation of PGPRs from a high-saline mangrove ecosystem in Abu Dhabi, with isolates exhibiting ACC deaminase (ACCD) activity to reduce stress-induced ethylene, along with additional plant growth-promoting (PGP) characteristics, including phosphate solubilization (P+). A total of 57 salt-tolerant bacterial isolates from the mangrove rhizosphere were initially screened for ACCD and P+ activities. Of these, 24 isolates tested positive for PGP characteristics and were further evaluated for their ability to enhance salt stress tolerance in tomato seedlings. In addition, seedlings inoculated …
Applications Of Archaeal Antioxidant Coenzyme M As An Agricultural Biostimulant, Jeremy Hunter Brown
Applications Of Archaeal Antioxidant Coenzyme M As An Agricultural Biostimulant, Jeremy Hunter Brown
Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–
As the demand to meet global food security goals continue to increase, the need to increase efficiency and productivity of agricultural output also rises. This calls for innovative and cost-effective methods for improving plant growth and yield. Here we explore how antioxidants, molecules that inhibit oxidation and are necessary for redox based signaling and redox homeostasis, can be utilized as chemical biostimulants. Specifically, we investigated Coenzyme M, an antioxidant from archaea that holds potential economic advantages over other antioxidants. Chapter 1 provides a comprehensive review of antioxidants and how exogenously application of them affects plant growth and biology, highlighting the …
Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.
Insulin Receptor Responsiveness Governs Tgfβ-Induced Hepatic Stellate Cell Activation: Insulin Resistance Instigates Liver Fibrosis, Wang-Hsin Lee, Evelyn A. Bates, Zachary A. Kipp, Sally Pauss, Genesee J. Martinez, Cheavar A. Blair, Terry D. Hinds Jr.
Markey Cancer Center Faculty Publications
The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the INSR gene in human LX2 HSC cells (INSRe5- 8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The INSRe5- 8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower TP53 expression that suppresses growth, and they also exhibited increased migration compared to the Scramble …
Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley
Predicting The Pathway Involvement Of Compounds Annotated In The Reactome Knowledgebase, Erik D. Huckvale, Hunter N. B. Moseley
Markey Cancer Center Faculty Publications
Background/Objectives: Pathway annotations of non-macromolecular (relatively small) biomolecules facilitate biological and biomedical interpretation of metabolomics datasets. However, low pathway annotation levels of detected biomolecules hinder this type of interpretation. Thus, predicting the pathway involvement of detected but unannotated biomolecules has a high potential to improve metabolomics data analysis and omics integration. Past publications have only made use of the Kyoto Encyclopedia of Genes and Genomes-derived datasets to develop machine learning models to predict pathway involvement. However, to our knowledge, the Reactome knowledgebase has not been utilized to develop these types of predictive models.
Methods: We created a dataset ready for …
Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li
Computational Design And In Vitro And In Vivo Characterization Of An Apoe-Based Synthetic High-Density Lipoprotein For Sepsis Therapy, Ling Guo, Yaxia Yuan, Fang Zhang, Chang-Guo Zhan, Xiangan Li
Markey Cancer Center Faculty Publications
Introduction: Septic patients have low levels of high-density lipoproteins (HDLs), which is a risk factor. Replenishing HDLs with synthetic HDLs (sHDLs) has shown promise as a therapy for sepsis. This study aimed to develop a computational approach to design and test new types of sHDLs for sepsis treatment. Methods: We used a three-step computational approach to design sHDL nanoparticles based on the structure of HDLs and their binding to endotoxins. We tested the efficacy of these sHDLs in two sepsis mouse models—cecal ligation and puncture (CLP)-induced and P. aeruginosa-induced sepsis models—and assessed their impact on inflammatory signaling in cells. Results: …
Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu
Artesunate Enhances The Efficacy Of Enzalutamide In Advanced Prostate Cancer, Xinyi Wang, Jinghui Liu, Fengyi Mao, Yifan Kong, Qiongsi Zhang, Chaohao Li, Daheng He, Chi Wang, Yanquan Zhang, Ruixin Wang, Sally R. Ellingson, Qiou Wei, Zhiguo Li, Xiaoqi Liu
Markey Cancer Center Faculty Publications
Prostate cancer (PCa) is one of the leading causes of death among men worldwide. Treatments targeting the androgen receptor pathway remain the standard therapy for PCa patients. Enzalutamide (ENZ), a second-generation androgen receptor inhibitor, was developed to treat castration-resistant prostate cancer. However, while patients initially respond to ENZ, drug resistance typically develops within a few months. Artesunate (ART), a semisynthetic derivative of the Artemisinin plant, is approved for antimalaria treatment. In this study, we conducted an FDA-approved drug screening and identified ART as a potential candidate for overcoming ENZ resistance in PCa. Mechanistically, ART induces the degradation of c-Myc, enhancing …
Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar
Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar
Chemistry & Biochemistry Faculty Publications and Presentations
Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …
Transcription Factor Binding And Discovery Of Novel Gene In The Opportunistic Human Pathogen, Pseudomonas Aeruginosa, Alaina Westee
Transcription Factor Binding And Discovery Of Novel Gene In The Opportunistic Human Pathogen, Pseudomonas Aeruginosa, Alaina Westee
Symposium of Student Scholars
Pseudomonas aeruginosa (PA) is a gram-negative, ubiquitously-found bacterium that primarily causes nosocomial, or hospital-borne, infections within immunocompromised patients. Therefore, it has been deemed a critical priority pathogen by the World Health Organization (WHO) and the Center for Disease Control (CDC), generating a need for research on its fundamental biology. The Van Dyke laboratory focuses on proteins called transcription factors, which promote or repress gene expression to regulate an organism’s functioning. We are specifically studying the cadmium-responsive transcription factor, CadR, due to the importance of metals in virulence and the lack of information on PA’s response to metal fluctuations. We intend …
A New Crispr System Uses Energy Storage Indiscriminately, Brendon Guinn
A New Crispr System Uses Energy Storage Indiscriminately, Brendon Guinn
Research on Capitol Hill
CRISPR systems are Immune systems used by bacteria to defend against viruses. Recently, tools such as CRISPR Cas9 that are derived from CRISPR systems have been developed as a powerful tool to treat disease.
Here we are studying a different CRISPR system related to the one used to develop the Cas9 tool. We study this system to discover new proteins that may be used to develop tools to cure diseases and diversify our arsenal of disease-fighting genetic sequences.
In-Silico Modeling And Characterization Of Kcc2 Protein Interaction With A Small Molecule Direct Agonist Identifies Potential Binding Sites For Modulating Behaviors Associated With Substances Of Abuse, William Hai Dang Ho, Alfred Amendolara, Kenyon Mitchell, Jaden Miner, Ruth Northcott, Braxton Bingham, Andrew J. Payne
In-Silico Modeling And Characterization Of Kcc2 Protein Interaction With A Small Molecule Direct Agonist Identifies Potential Binding Sites For Modulating Behaviors Associated With Substances Of Abuse, William Hai Dang Ho, Alfred Amendolara, Kenyon Mitchell, Jaden Miner, Ruth Northcott, Braxton Bingham, Andrew J. Payne
Annual Research Symposium
Purpose
KCC2 is a potassium-chloride cotransporter that plays a critical role in neuronal function by regulating GABAergic signaling via chloride gradients. Maintaining this concentration gradient is crucial for balancing excitation and inhibition in the brain. While KCC2 dysregulation has been implicated in epilepsy and seizures, recent studies suggest that KCC2 inhibition results in phenotypes mirroring those seen in chronic opioid dependence. As such, increasing evidence support KCC2 being a potential therapeutic target for modulating behaviors associated with substances of abuse. Currently, only a few direct small molecule agonists against KCC2 have been reported, and no definitive active site on the …
Probing The Stability Of Designed Protein, Axel Irianni, Shuvo Chakraborty, Maral Afshinpour
Probing The Stability Of Designed Protein, Axel Irianni, Shuvo Chakraborty, Maral Afshinpour
SDSU Data Science Symposium
Naturally occurring proteins have evolved to perform specific biochemical functions, and their amino acid sequences are optimized for those functions rather than for stability. Enhancing protein stability without compromising its function is highly desirable for biotechnological applications, such as vaccine design. Computational protein design algorithms offer a solution by making targeted amino acid changes to the native protein sequence, potentially enhancing stability without the need for the lengthy, labor-intensive, and costly experimental processes typically involved in stabilizing proteins. There are various categories of computational protein design algorithms, and it remains unclear which approach is the most effective. In this study, …
Single Amino Acid Changes Impact The Ability Of Drosophila Melanogaster Cecropins To Inhibit Growth Of Providencia Pathogens, Sarah Smith, Marla Forfar, Christopher Feudale, Lauren Shaffer, Grace Ginder, Marion Duval, Quinn Smith, Moria C. Chambers
Single Amino Acid Changes Impact The Ability Of Drosophila Melanogaster Cecropins To Inhibit Growth Of Providencia Pathogens, Sarah Smith, Marla Forfar, Christopher Feudale, Lauren Shaffer, Grace Ginder, Marion Duval, Quinn Smith, Moria C. Chambers
Faculty Journal Articles
As antibiotic-resistant bacteria spread worldwide, the need to develop novel antimicrobial agents is urgent. One rich source of potential antimicrobials is the insect immune system, as insects produce a wide range of antimicrobial peptides (AMPs) with diverse sequences and structures. Insects also encounter many bacterial pathogens, some of which are closely related to pathogens of clinical relevance. However, despite interest in AMPs as therapeutics, the relationships between the amino acid sequence, biophysical properties, antimicrobial activity, and specificity are still not generalizable. To improve our understanding of these relationships, we assessed how single amino acid changes in cecropin AMPs produced by …
The Lc3-Interacting Region Of Nbr1 Is A Protein Interaction Hub Enabling Optimal Flux, Brian Joseph North
The Lc3-Interacting Region Of Nbr1 Is A Protein Interaction Hub Enabling Optimal Flux, Brian Joseph North
Dartmouth College Ph.D Dissertations
Autophagy is a highly conserved pathway that maintains cell health by breaking down and recycling cellular components such as protein aggregates or damaged organelles. During autophagy, potentially toxic cargo is enveloped by a newly formed autophagosome and trafficked to the lysosome for degradation. Ubiquitinated protein aggregates, a key target for autophagy, are identified by multiple autophagy receptors. NBR1 is an archetypal autophagy receptor and an excellent model for deciphering the role of the multivalent, heterotypic interactions made by cargo-bound receptors. Using NBR1 as a model, we find that three critical binding partners—ATG8-family proteins, FIP200, and TAX1BP1—each bind to a short …
Inhibition Of Lysine Deacetylase Activity Impacts Formation Of The Vitamin D Receptor Activation Complex, Shannon Dwyer
Inhibition Of Lysine Deacetylase Activity Impacts Formation Of The Vitamin D Receptor Activation Complex, Shannon Dwyer
Theses and Dissertations
The vitamin D endocrine system is responsible for the regulation of many biological processes including bone metabolism, calcium homeostasis, cell proliferation and cell differentiation. Alterations to the vitamin D signaling pathway are associated with several diseases including bone diseases, diabetes, cardiovascular diseases, autoimmune diseases, and cancer. Vitamin D precursors are chemically modified to become the biologically active hormone, calcitriol. Calcitriol binds to the vitamin D receptor (VDR), a member of the nuclear hormone receptor (NHR) superfamily. VDR forms a heterodimer with retinoid X receptor (RXR) and together they bind to promoters containing vitamin D response elements (VDREs) to activate transcription …
Ivy Proteins As Guardians Of Bacterial Cell Wall Integrity: Regulation Of Lytic Transglycosylases Explored, Aamna Aijaz, Trinity E. Alamutu, Vy T. Dao, Nathaniel R. Davis, Michael D. Landers, Nykolas K. Mackevicius, Liliana Ortiz, Irina F. Padilla-Montoya, Kacy J. Smith, Maria L. Snyder, Anthony J. Stefanie, Blaise M. Williams, Thomas C. Leeper
Ivy Proteins As Guardians Of Bacterial Cell Wall Integrity: Regulation Of Lytic Transglycosylases Explored, Aamna Aijaz, Trinity E. Alamutu, Vy T. Dao, Nathaniel R. Davis, Michael D. Landers, Nykolas K. Mackevicius, Liliana Ortiz, Irina F. Padilla-Montoya, Kacy J. Smith, Maria L. Snyder, Anthony J. Stefanie, Blaise M. Williams, Thomas C. Leeper
The Kennesaw Journal of Undergraduate Research
Lytic transglycosylases (LTs) are bacterial enzymes involved in biosynthesis and maintenance of the peptidoglycan cell wall. LTs are reported to be regulated by two paralogs of Inhibitor of Vertebrate Lysozymes: Ivyp1 and Ivyp2. This study investigated the regulatory dynamics between the soluble LT (SltB1), and Ivy paralogs as putative regulators in Pseudomonas aeruginosa (PA). The secondary objective was to delineate the critical roles played by a glutamic acid at position 135 in SltB1 and a histidine at position 62 in Ivyp1 in governing their molecular interaction through site directed mutagenesis. Isolated SltB1 shows no lytic activity in our assay, in …