Life Sciences Commons^™

Positron Emission Tomography In Oncology And Environmental Science, Samantha Delaney

Dissertations, Theses, and Capstone Projects

The last half century has played witness to the onset of molecular imaging for the clinical assessment of physiological targets. While several medical imaging modalities allow for the visualization of the functional and anatomical properties of humans and living systems, few offer accurate quantitation and the ability to detect biochemical processes with low-administered drug mass doses. This limits how physicians and scientists may diagnose and treat medical issues, such as cancer, disease, and foreign agents.

A promising alternative to extant invasive procedures and suboptimal imaging modalities to assess the nature of a biological environment is the use of positron emission …

Neuroinflammation Levels Measured By Microglial Cell Activation, Emma G. Whitlock, Linda S. Yasui

Honors Capstones

Neuroinflammation is an inflammatory response in the brain that can be caused by different stressors such as diseases and/or external factors such as traumatic brain injuries. It is important to note duration and intensity of neuroinflammation levels when determining the impacts of these stressors to the brain environment. During neuroinflammation, a type of immune cell that becomes activated in the brain is called microglial cells. Microglial cells play a role in progression of the pathophysiological effects from the brain stressor. Studying changes in microglial cell shape provides evidence of the degree of neuroinflammation in the brain. Researchers can quantify neuroinflammation …

Investigation Of Avaren-Fc's Therapeutic Potential Against Ovarian Cancer., Katarina Lee Mayer

Electronic Theses and Dissertations

This thesis describes the investigation of Avaren-Fc (AvFc), a novel lectin-based therapeutic fusion protein consisting of the recombinant Avaren lectin and the Fc region of human IgG1, against ovarian cancer. AvFc possesses selectivity toward tumor associated N-linked high-mannose-type glycans. The present study demonstrates AvFc’s in vitro activity against OVCA cell lines via antibody-dependent cell-mediated cytotoxicity and its ability to extend the survival of mice challenged with murine ID8 OVCA cells after repeated systemic administration. Furthermore, AvFc treatment in this model was found to increase the presence of peritoneal leukocytes, suggesting a shift toward an improved antitumor immune response. Another key …

Production And Characterization Of Monoclonal Antibodies To Xenopus Proteins, Brett A. Horr

Masters Theses

Monoclonal antibodies are powerful and versatile tools that enable the study of proteins in diverse contexts. They are often utilized to assist with identification of subcellular localization and characterization of the function of target proteins of interest. However, because there can be considerable sequence diversity between orthologous proteins in Xenopus and mammals, antibodies produced against mouse or human proteins often do not recognize Xenopus counterparts. To address this issue, we refined existing mouse monoclonal antibody production protocols to generate antibodies against Xenopus proteins of interest. Here, we describe several approaches for the generation of useful mouse anti-Xenopus antibodies to multiple …

Evaluation Of The Humoral Immune Responses To Plasmodium Vivax Circumsporozoite Protein (Csp)-Based Pre-Erythrocytic Vaccine Candidates, Jack Esquenazi

USF Tampa Graduate Theses and Dissertations

Malaria, caused by the apicomplexan Plasmodium spp. , is a major public health issue that impacts over one-third of the world’s population ,with Plasmodium vivax accounting for over 130 million clinical cases annually. The circumsporozoite protein (CSP) is the most abundant molecule on the surface of Plasmodium sporozoites and is considered a leading pre-erythrocytic stage vaccine candidate. CSP is essential for sporozoite maturation, migration, and invasion. Anti-CSP antibodies interrupt sporozoite migration and infection of hepatocytes thus reducing liver-stage burden. P. vivax CSP is composed of three subdomains: a highly polymorphic immunodominant central repeat region (CRR), conserved N-terminal ,and C-terminal subdomains. …

Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.

Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …

Staphylococcal Surface Proteins As Vaccine Candidates For The Control Of Staphylococcal Mastitis In Dairy Cows, Jessica Jean Vidlund

Masters Theses

Bovine mastitis, an inflammation of the mammary gland, is the single most costly disease of dairy cattle. Staphylococci, a major bacteria that cause bovine mastitis, are commonly divided into two major groups: Staphylococcus aureus and non-aureus staphylococci (NAS), previously known as coagulase-negative Staphylococcus species (CNS). Current mastitis control programs are not fully effective against staphylococcal mastitis and antibiotics are not sustainable due to limited success and the emergence of antimicrobial resistant bacteria. Non-antibiotic sustainable control tools, such as effective vaccines, are critically needed. Our lab developed and evaluated Staphylococcus aureus surface associated protein (SASP) and Staphylococcus chromogenes surface associated protein …

Fine-Mapping Of Human Antibody Specificity In Response To Natural Chlamydia Trachomatis Infection Utilized To Inform Vaccines Against Adhesion Factors, Amanda L. Collar

Biomedical Sciences ETDs

Chlamydia trachomatis (Ct) is the causative pathogen for the most common bacterial sexually transmitted infection worldwide and can cause serious medical consequences in women, including pelvic inflammatory disease, ectopic pregnancy, and infertility. For these reasons, a Ct vaccine is urgently needed, yet, its development remains a significant challenge. One barrier to producing a Ct vaccine is the gap in knowledge of protective immune responses for Ct infection, including the role that antibodies may play. Therefore, I aimed to characterize the human antibody response to natural urogenital Ct infection in women using Deep Sequence-Coupled Biopanning. Further, I leveraged these findings to …

Development And Characterization Of B7-H3-Targeted Radioimmunotherapies For The Treatment Of Solid Tumors, Sarah Glazer

Dissertations & Theses (Open Access)

Radioimmunotherapy involves the selective targeting of therapeutic radionuclides to cancer-associated cell surface antigens using monoclonal antibodies. Radioimmunotherapy has been successful in treating hematologic cancers, such as non-Hodgkin’s Lymphoma. However, treatment of solid tumors by radioimmunotherapy remains a challenge, driven in part by a lack of high affinity antibodies against highly tumor-selective surface antigens. Herein, we characterize novel anti-B7-H3 immuno-conjugates for PET imaging and RIT of solid tumors in preclinical models.

Human B7-H3 (CD276) protein is highly expressed on solid tumor cell surfaces and endovascular surfaces in a wide variety of cancers (colon, breast, pancreatic, prostate, head and neck, glioblastoma, ovarian, …

Immunohistochemistry Of The Zebrafish Retina, Alison Ruf

Williams Honors College, Honors Research Projects

The retina is made up of many different essential parts that work together to allow for vision of many different species. Some of these crucial cells and proteins include ganglion cells, bipolar cells, photoreceptors, synaptic markers, such as VGLUT, and receptors that bind glutamate. The basis of this project is to use immunohistochemistry to identify these important aspects of the retina in zebrafish via monoclonal and polyclonal antibodies. The goal being to compare specific cells in a control group retina to an experimental group of zebrafish.

A Multi-Resolution Graph Convolution Network For Contiguous Epitope Prediction, Lisa Oh

Dartmouth College Master’s Theses

Computational methods for predicting binding interfaces between antigens and antibodies (epitopes and paratopes) are faster and cheaper than traditional experimental structure determination methods. A sufficiently reliable computational predictor that could scale to large sets of available antibody sequence data could thus inform and expedite many biomedical pursuits, such as better understanding immune responses to vaccination and natural infection and developing better drugs and vaccines. However, current state-of-the-art predictors produce discontiguous predictions, e.g., predicting the epitope in many different spots on an antigen, even though in reality they typically comprise a single localized region. We seek to produce contiguous predicted epitopes, …

Nucleic Acids Promote Oligomerization Of Immunoglobulin G, Alexa Gomez

Electronic Theses and Dissertations

Nucleic acids have been found to prevent aggregation as chaperones, as well as act as co-factors and promote aggregation of amyloidogenic proteins leading to various diseases. Immunoglobulin G, IgG, are prone to aggregate as therapeutic proteins, and light chains of IgG can form amyloid fibrils, causing a disease known as light chain amyloidosis. Here we discuss the effect nucleic acids have on full-length immunoglobulin G aggregation. Our results show G-quadruplex DNA, and bulk DNA lead to oligomerization of full-length IgG, and induce increases in secondary structure. Tryptophan fluorescence indicates structural changes are occurring in the presence of DNA. Additionally, IgG …

Determinants Of Antibody Immunity In Flavivirus Infections And Immunization, Huy Tu

Graduate College Dissertations and Theses

The most significant arthropod-borne viral infections in modern history are caused by species of the Flavivirus (FV) genus due to their global transmission. While immunization is effective at decreasing the burden imposed by some FV, vaccines for other FV such as Dengue virus (DENV) and Zika virus (ZIKV) are still in development or not widely available. A better understanding of the protective immune response, specifically the antibody response, to DENV and ZIKV will advance the vaccine development endeavors for these viruses. Utilizing longitudinal samples from controlled human immunization/challenge studies and natural infections, we investigated the antibody response to these viruses …

Effect Of Fecal Egg Count Estimated Breeding Value On Antibody Production In Katahdin Lambs, Kelsey L. Bentley

Graduate Theses, Dissertations, and Problem Reports

With current pressures to seek out genetic solutions to combat antimicrobial resistance, genetic resistance to the gastrointestinal nematode Haemonchus contortus may reduce need for prophylactic antibiotic use. The Katahdin breed has effectively utilized post-weaning fecal egg count estimated breeding value (PFEC EBV) to reduce parasitism within their flocks, but there still remains significant opportunity for selection within breed. In a previous study, Katahdin sheep sired by low PFEC sires had greater survivability to weaning than lambs sired by high PFEC rams and preweaning was caused by other diseases than parasitism. Those data lead to the hypothesis that selection for PFEC …

Exploring Interleukin 21 And Its Role In Humoral Immunity In The Mouse Model Of Influenza Infection, Samantha E. Gallahan

Honors Undergraduate Theses

In summary, this study will be focused on Il-21 and its implications in the antibody response in influenza. The isotype classes primarily involved in this process will also be examined. This will be accomplished by looking at the serum of mice and analyzing the present influenza specific antibodies using ELISA. Another goal was to optimize the ELISA in order to make it sensitive enough to catch small differences in the results. This topic is important due to its implications for improving influenza vaccinations and preventions as current vaccines are not 100% effective. Influenza contributes to significant disease and death around …

Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka

Legacy Theses & Dissertations (2009 - 2024)

Ricin is a highly lethal protein toxin derived from the seeds of the castor plant, Ricinus communis. It is a Type II ribosome inactivating protein (RIP), meaning it is a heterodimer with one subunit, ricin toxin B (RTB), that mediates cell surface attachment and intracellular trafficking and a second subunit, ricin toxin A (RTA), that irreversibly shuts down protein synthesis in the cytosol. During trafficking, RTA and RTB necessarily separate in the endoplasmic reticulum, wherein RTA unfolds and translocates into the cytosol where it refolds into an enzymatically active conformation. RTA is remarkably fast acting and efficient, with few molecules …

Passive Immunization Against Invasive Salmonella Enterica, Angelene Richards

Legacy Theses & Dissertations (2009 - 2024)

The Gram-negative bacterium, Salmonella enterica is a prominent etiologic agent of both diarrheal disease and enteric fever that encompasses over 2500 serovars, including S. Typhimurium (STm) and S. Typhi (STy). S. enterica is transmitted through contaminated food and water and, following ingestion, invades the gastrointestinal (GI) mucosa. The bacterium uses flagellar-based motility to target microfold (M) cells overlying gut-associated lymphoid tissues known as Peyer’s patches in the small intestine. Entry into Peyer’s patch tissues is a pivotal step in the infection process, as the bacterium can then disseminate systemically in the host. Given the rise in antibiotic resistance amongst S. …

The Kinetic Signatures Of Antibody Binding To M. Genitalium Adhesin Protein Fragments, Margaret C. Lunn

Honors Projects

Mycoplasma genitalium is a sexually-transmitted bacterial pathogen that persists in patients by adherence to cells through matrix glycoproteins and evasion of host antibodies. The MgpB and MgpC adherence proteins consist of variable and conserved regions. Variable regions undergo antigenic variation to avoid specific antibodies. However, the C-terminus (MgpB-4a) does not vary, is highly immunogenic, and antibodies to this region inhibit attachment and promote bacterial killing in vitro. To better understand how M. genitalium avoids clearance by antibodies to MgpB-4a in vivo we used surface plasmon resonance (SPR) to measure kinetic values of binding events. Binding of polyclonal rabbit antibodies (3935 …

Review Of The Latest Trends In Transplantation Immunology And Its Role In Mortality Reduction, Vivian Adedoye

Honor’s College Freeman Research Journal

Transplantation immunology deals with the process of moving cells, tissues, or organs, from one site to another, either within the same person or between a donor and a recipient. If an organ system fails, or becomes damaged because of disease or injury, it can be replaced with a healthy organ or tissue from a donor. The process of transplantation has become increasingly popular due to its life saving benefit. In 2015 /2016 4601 patients' lives were saved or improved by an organ transplant in the United Kingdom alone. Kidney transplants are the most common organ transplant followed by liver and …

Haemonchus Contortus Antigen Identification And Use Of Tropomyosin In Ovine Vaccine Development, Brynnan P. Russ

Graduate Theses, Dissertations, and Problem Reports

Globally, the small ruminant industry loses hundreds of millions of dollars due to parasitism by the gastrointestinal nematode Haemonchus contortus. This parasite feeds on blood in the host’s abomasum leading to disease including anemia, hypoproteinemia, lethargy, and death. There have been exhaustive efforts to manage this parasite including different management applications, anthelmintic treatment, and now integration of resistance genetics into a flock. Like antibiotics, overuse of anthelmintics has led to resistance of H. contortus to these drugs. Therefore, other methods of control are the main focuses of many research initiatives. St. Croix are a resistant breed of sheep that mount …

Germinal Center B Cell Expression Of Aire Regulates Antibody Diversification And Autoimmunity, Jordan Zheng Zhou

Wayne State University Dissertations

B cells are a unique subset of immune cells that, in response to antigen, diversify their antibody repertoire to generate progressively higher affinity antibodies of different isotypes through the processes of affinity maturation/somatic hypermutation (SHM) and class switch recombination (CSR). One of the major sites in which this diversification occurs is in T cell dependent microanatomical structures known as germinal centers (GC). Here, we find that GC B cells express the protein, autoimmune regulator (Aire) in a CD40 dependent manner. In these cells, Aire interacts with activation induced cytidine deaminase (AID), the protein responsible for initiating the processes of diversification …

Single-Domain Alpaca Antibodies That Disrupt Ricin Toxin Uptake And Trafficking In Mammalian Cells, Amanda Yee Poon

Legacy Theses & Dissertations (2009 - 2024)

Ricin is a member of the ribosome-inactivating protein (RIP) family of toxins found throughout the plant and microbial worlds. In its mature form, ricin is a 65 kDa glycoprotein consisting of two subunits, RTA and RTB, joined by a single disulfide bond. RTA (267 amino acids) is an RNA N-glycosidase that mediates the depurination of a universally conserved residue within the Sarcin-ricin loop (SRL) ribosomal RNA element. RTB is a galactose-/N-acetylgalactosamine-specific lectin that facilitates attachment, endocytosis, and intracellular trafficking of ricin in mammalian cells. Following endocytosis, ricin is routed to the trans-Golgi network (TGN) and then shuttled to the endoplasmic …

Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova

Legacy Theses & Dissertations (2009 - 2024)

The outer membrane (OM) of Gram-negative enteric pathogens like Vibrio cholerae is a barrier against host defense factors, as well as a sensor of physical and chemical stimuli that the bacteria encounter in the gastrointestinal tract. The OM is also the primary target of the mucosal immune response, which consists of secretory antibodies primarily directed against lipopolysaccharide (LPS). ZAC-3 is a monoclonal antibody (MAb) that targets the conserved core/lipid A region of LPS of the pandemic V. cholerae O1 serotype. In a neonatal mouse model, passively administered ZAC-3 IgG has been shown to reduce the ability of V. cholerae to …

Engineering Of An Antibody-Conjugated Nanogel Platform For Targeted Drug Delivery To T Lymphocytes, Mine Canakci

Doctoral Dissertations

In an ideal chemotherapy, cytotoxic drugs travel through the bloodstream, reach cells all over the body and preferentially kill abnormal cells. Yet, the hydrophilic or lipophilic property of the small-molecule drugs affects their ability to reach cells from the bloodstream. So, only a small portion of the drug reaches to the diseased tissue. A selective cell killing approach for cancer therapy gained momentum after the realization that cancer cells carry unique set of molecular markers on their cell surface. The development of antibody drug conjugates (ADC) revolutionized the targeted approach for drug delivery. ADCs are composed of cytotoxic agents covalently …

Cross-Presentation Is A Source Of Tumor Antigens For Multiple Myeloma Immunotherapy, Alexander A. Perakis

Dissertations & Theses (Open Access)

Cross-presentation is an essential bridge between the innate and adaptive arms of the immune system where antigen presenting cells (APCs) prime cytotoxic T cell responses. We have recently identified cross-presentation as a mechanism by which solid tumors present exogenous antigens. We therefore hypothesized that multiple myeloma would be capable of cross-presentation as these cells are derived from B cells, known APCs. We explored the capacity of multiple myeloma to cross-present PR1, a human leukocyte antigen (HLA)-A2 nonameric peptide that is derived from neutrophil elastase (NE) and proteinase 3 (P3), and the ability to treat multiple myeloma using PR1-targeting immunotherapies. Here …

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

Analysis Of The Molecular Mechanisms Governing Fcγ Receptor Activation On The Surfaces Of Macrophages By Advanced Optical Microscopy, Elizabeth Michelle Bailey

Electronic Theses and Dissertations

Therapeutic antibodies are achieving new levels of therapeutic success in treating cancers and immunological disorders by antibody engagement of Fc receptor-directed immune responses. Conversely, inhibiting autoantibody induced Fc receptor activation is an attractive approach to treat autoimmune diseases. Immunoglobulin G (IgG) antibodies are often the principal subclass used in therapeutic antibodies and associated with autoimmune pathologies because of their long circulation and potent effector functions, including activation of the Fcγ Receptor (FcγR). Thus, a thorough understanding of the FcγR activation is required to improve the efficacy of immunotherapies and to mitigate autoimmunities. It is well established that FcγR clustering is …

Cd147 As A Potential Therapeutic Target In Glioblastoma Treatment, Beau Adams

All NMU Master's Theses

Glioblastoma (GBM) tumors are the most common and lethal form of cancer in the central nervous system (CNS). GBM tumors appear to contain a mixture of different cell types, which makes them difficult to treat. GBM cells exhibit altered morphology from normal cells on several different levels, which highlights different pathways to potentially target for therapeutic treatments. The human surface glycoprotein CD147, also known as basigin, is expressed at significantly higher levels in GBMs compared to non-neoplastic brain tissue. Furthermore, levels of CD147 expression correlate with brain tumor progression and show the highest expression in GBM. Here, we suppressed tumor …

Design And Development Of A Quartz Crystal Microbalance Immunosensor For Exosomes, Wesley Cox

Chancellor’s Honors Program Projects

No abstract provided.

The Subcloning And Expression Of Munc18a In Escherichia Coli For Antibody Production And Analysis In Mast Cell Degranulation Reactions, Brandi Goble

Honors Theses

Mast cells are secretory cells responsible for fighting off infection through the early recognition of pathogens. This process is completed through the secretion of proinflammatory mediators that are stored in secretory granules within the cytoplasm of the cell. The degranulation secretion process relies on regulated fusion of secretory granules to the cell membrane via membrane-bound SNARE proteins that bridges the two opposed membranes. The intricate regulation of SNARE-mediated mast cell degranulation is not well understood. However, Sec1/Munc18 (SM) proteins, specifically the Munc18 isoforms, are known to play a critical role in the process (Brochetta, et. al., 2014). The Xu lab …