Biochemistry, Biophysics, and Structural Biology Commons^™

Extension Of The Ergot Alkaloid Gene Cluster, Samantha Joy Fabian

Graduate Theses, Dissertations, and Problem Reports (ETD)

Specialized metabolites produced by fungi impact human health. A large portion of the pharmaceuticals currently on the market are derived from metabolites biosynthesized by microbes. Ergot alkaloids are a class of fungal metabolites that are important in the interactions of environmental fungi with insects and mammals and also are used in the production of pharmaceuticals. In animals, ergot alkaloids can act as partial agonists or antagonists at receptors for 5-hydroxytryptamine (serotonin), dopamine, and noradrenaline as ergot alkaloids have chemical structures similar to those neurotransmitters. Therefore, they affect insects and mammals that consume them and can be used to produce drugs …

The Role Of Cadherins And Ryk On Metastasis And Invasion In Triple Negative Breast Cancer Cell Model: Hs578t/Hs578ts(I)8, Ibis Iser

Electronic Theses and Dissertations

Breast cancer is a major cause of death among women in European and North American countries, even with improved methods for diagnosis and therapy. The mortality of breast cancer is mainly due to the migration of the primary tumor to distinct sites in the body and is very common in triple negative breast cancer (TNBC). This type of breast cancer affects younger woman and has a high recurrence rate. Unfortunately, TNBC is extremely difficult to control because of the absence of specific targets for treatment. Therefore, our research aim is to discover new therapeutic targets and identify novel approaches for …

Modulatory Effects Of Deacetylated Sialic Acids On Breast Cancer Resistance Protein-Mediated Multidrug Resistance And Receptor Tyrosine Kinase-Targeted Therapy, Isaac Tuffour

Electronic Theses and Dissertations

Multidrug resistance (MDR) remains a major challenge in cancer treatment, accounting for over 90% of chemotherapeutic failures. Cancers utilize sugar residues to engage in multidrug resistance. The underlying mechanism of action involving glycans, specifically the glycan sialic acid (Sia) and its various functional group alterations, has not been explored. ATP-binding cassette (ABC) transporter proteins, key proteins utilized by cancers to engage in MDR pathways, contain Sias in their extracellular domains. Modulating the expression of acetylated-Sias on Breast Cancer Resistance Protein (BCRP), a significant ABC transporter implicated in MDR, in lung and colon cancer cells directly impacted the ability of cancer …

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

Food Waste Storage Gaseous Emissions Detection And Quantification Using Infrared Spectroscopy, Ryley A. Burton-Tauzer

Cal Poly Humboldt theses and projects

A growing interest in sustainable waste management and the implementation of new policies have prompted a shift towards alternative resource recovery methods for organic waste, including food waste. To effectively assess alternative food waste treatment scenarios, it is important to evaluate the life cycle impacts associated with each scenario. The storage phase of food waste, encompassing its accumulation in kitchens, and storage in bins for collection and transportation, has been overlooked as a source of greenhouse gases in previous studies. This investigation aimed to identify the greenhouse gases emitted during the initial five-day period of low-oxygen storage. An open dynamic …

Natural Variation In Temperature-Modulated Immunity To Pseudomonas Syringae Pv. Tomato (Pst Dc3000) In Arabidopsis Thaliana Plants, Christina A. M. Rossi

Theses and Dissertations (Comprehensive)

Studies conducted on the model plant-pathogen system Arabidopsis thaliana-Pseudomonas syringae pv. tomato (Pst) showed that elevated temperature suppresses the pathogen-induced production of salicylic acid (SA), which is a key plant defence hormone. This increased host vulnerability at higher temperatures is due to downregulated expression of CALMODULIN BINDING PROTEIN 60-LIKE G (CBP60g) and SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1), which encode master regulators of SA production. Collectively, these previous studies only focused on one natural accession of Arabidopsis called Columbia-0 (Col-0). However, the intraspecific variation in Arabidopsis immunity phenotypes under elevated temperature remains unknown. To fill this critical knowledge gap, my …

Functional Residues Of Cjpata, Robert Lamont

Theses and Dissertations (Comprehensive)

Antibiotic resistance in pathogenic bacteria continues to challenge clinicians and threaten the lives of infected individuals. For this reason, new classes of antibiotics or new targets for antibiotic therapy are needed to circumvent this global health crisis. In Gram-negative bacteria, the enzymes peptidoglycan O-acetyltransferase A and B (PatA and PatB), are responsible for adding acetyl groups to the C-6 hydroxyl group of N-acetyl muramic acid (MurNAc) in peptidoglycan (PG). These acetyl groups are responsible for inhibiting the activity of lysozyme from host organisms that hydrolyze the β1-4 glycosidic linkage between MurNAc and N-acetylglucosamine (GlcNAc). The acetyl groups …

Exploring The Membrane Protein And Peptide Interactions Of Mitochondrial And Bacterial Lipid Systems, George Saudan

Theses and Dissertations (Comprehensive)

This study aims to expand the understanding of interactions between membrane lipids and proteins, and relate it to their biological functions in two experimental systems. The first system focuses on the interaction and conformation of a membrane protein Uncoupling Protein 4 (UCP4) in mitochondrial inner membrane lipids, in the absence and presence of cardiolipin; a lipid specific to mitochondrial inner membranes. The second system considers the interaction and conformation of a cell penetrating peptide, Penetratin, which can interact with both mammalian and bacterial cells. A N- and C-termini protected form of this 16-meric peptide (Pen2) was used to explore its …

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 …

Assessing The Biocatalytic Promiscuity Of Pep- Transformations For Geminal-Difluorination, Eloy Jose Torres Garcia

Theses and Dissertations (Comprehensive)

Fluorine is the most electronegative chemical element and can drastically change molecular properties, such as drug pharmacokinetics and agrochemical half-life. Although a great deal of progress is occurring in synthetic methods to access various organofluorines, these methods struggle with harsh conditions and limited substrate scope. Biocatalytic approaches offer the potential to access organofluorines that are difficult or impossible with the current methodology. Phosphoenolpyruvate (PEP) is a central metabolite and biosynthetic precursor for diverse molecules. Phosphoenol pyruvate mutase (Ppm) catalyses the interconversion of Phosphonopyruvate (PnPy) to Phosphoenolpyruvate (PEP). This research successfully expressed and …

Characterization Of The Clostridioides Difficile Glycosyl Hydrolase Ccsz, Brian Lowrance

Theses and Dissertations (Comprehensive)

Bacteria inhabit many of the harshest environments on Earth; persisting and thriving in conditions thought to be unsuitable for life. One common strategy to withstand these environments is the formation of a biofilm. Biofilm composition varies greatly, depending on the underlying community that produces it. Cellulose, a polymer consistently prevalent in biofilms, has been identified as a virulence factor in many pathogens and is suspected to be involved in pathogenesis by Clostridioides difficile. C. difficile is the #1 cause of hospital acquired diarrhea, which can range from mild to life-threatening infections. Biofilm formation is hypothesized to be involved in …

Gestational Vulnerability To Ozone Air Pollution - A Placental Story, Vishnupriya Alavala, Sarah Brent, Russell Hunter, Matthew J. Campen, Andrew Ottens

UROP Posters

About 99% of the global population resides in areas with air pollution surpassing World Health Organization standards. Air pollution is associated with adverse neonatal health outcomes such as low fetal birth weight and an increased risk for maternal pre-eclampsia. A particularly reactive air pollutant is ozone, which forms reactive oxygen species that induce cellular damage. Research exists on the dispersion of reactive oxygen species through the bloodstream leading to fetal vulnerability during pregnancy, specifically via the placenta. Yet, placental and fetal development is a temporal process with varied susceptibility to negative gestational outcomes.

To addressing this gap, our laboratory utilized …

Structural Analysis Of Predicted Proteins Using Alphafold, Brydon P. Wall

UROP Posters

The function of around 67% of predicted proteins from genes in Mycobacteriophage CheetoDust can not be confidently predicted using traditional techniques and can only be functionally labeled “hypothetical proteins”. However, a new approach using AlphaFold, an artificial intelligence tool to generate a structural prediction from a sequence, can take advantage of structurally conserved regions that were previously obfuscated to gain new insights and visualize data in new ways.

Since amino acid sequences are more conserved than its corresponding DNA sequence, amino acid sequences are used when predicting the function of the corresponding translated protein. Until recently, predicting structure from an …

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …

Quantitative Measurement Of Protac Intracellular Accumulation, Xin Yu, Jin Wang

Faculty, Staff and Students Publications

In recent years, Proteolysis Targeting Chimera (PROTAC) technology has emerged as one of the most promising approaches to remove disease-associated proteins by utilizing cells' own destruction machinery. To achieve successful degradation of a protein of interest (POI), the heterobifunctional PROTAC molecules must penetrate into the cells first, followed by target engagement and formation of the POI-PROTAC-E3 ligase complex. Based on this understanding, the assessment of cell permeability and in cell target engagement are of great importance to evaluate the efficacy of PROTAC candidates. PROTAC molecules can be classified as non-covalent and covalent, and covalent PROTACs can be further divided into …

How Do Necrotic Cells Expose Phosphatidylserine To Attract Their Predators-What’S Unique And What’S In Common With Apoptotic Cells, Yoshitaka Furuta, Zheng Zhou

Faculty, Staff and Students Publications

Phosphatidylserine (PS) is a lipid component of the plasma membrane. It is asymmetrically distributed to the inner leaflet in live cells. In cells undergoing apoptosis, phosphatidylserine is exposed to the outer surfaces. The exposed phosphatidylserine acts as an evolutionarily conserved “eat-me” signal that attracts neighboring engulfing cells in metazoan organisms, including the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and mammals. During apoptosis, the exposure of phosphatidylserine to the outer surface of a cell is driven by the membrane scramblases and flippases, the activities of which are regulated by caspases. Cells undergoing necrosis, a kind of cell …

Mortality Difference From Klebsiella Aerogenes Vs Enterobacter Cloacae Bloodstream Infections, Andrew Chou, Richard Sucgang, Richard J Hamill, Lynn Zechiedrich, Barbara W Trautner

Faculty, Staff and Students Publications

Members of the order Enterobacterales, including Escherichia coli , Klebsiella species and Enterobacter species, are important pathogens in healthcare-associated infections. Higher mortality has been reported from infections due to Klebsiella pneumoniae than from E. coli , but prior studies comparing Enterobacter aerogenes (recently renamed Klebsiella aerogenes ) bacteraemia and Enterobacter cloacae complex bacteraemia have yielded conflicting results regarding whether clinical outcomes differ. We found bacteraemia with K. aerogenes was independently associated with greater risk of 30-day mortality than bacteraemia with Enterobacter cloacae complex.

A Rare Case Of Pancreatic Actinomyces, Marguerite Poche, Kyle Liu, Codey Pham, Shilpa Jain, Robert Sealock

Faculty, Staff and Students Publications

Actinomyces israelii is a filamentous, gram-positive anaerobic bacterium commonly found in the upper gastrointestinal tract, colon, and female genital tract. Rarely, actinomycosis can infect the pancreas most commonly after pancreatic instrumentation, often mimicking malignancy. We describe a case of a 26-year-old woman who presented with epigastric abdominal pain and nausea without prior pancreatic instrumentation. Abdominal imaging demonstrated a mass in the pancreatic head with fine-needle biopsy revealing Actinomyces. The patient was successfully treated with long-term antibiotic therapy resulting in resolution of the mass. Our case emphasizes the importance of considering nonmalignant etiologies in the differential diagnosis of pancreatic masses.

Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson

Faculty, Staff and Students Publications

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation …

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Yan-Hao Wei, Ren-Tang Bi, Yan-Mei Qiu, Chun-Lin Zhang, Jian-Zhuang Li, Ya-Nan Li, Bo Hu

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …