Biochemistry Commons^™

Metabolic Reprogramming In Kras-Driven Cancer Cells, Ahmet Hatipoglu

Dissertations, Theses, and Capstone Projects

Cancer cells require nutrient uptake for anabolic reactions needed for cellular growth and proliferation. The mammalian target of rapamycin (mTOR) is a key regulator of cellular growth that links nutrient availability and growth factor signals. mTOR mediated signaling pathways are often dysregulated in a wide range of cancers. We previously reported that KRas-driven cancer cells sense exogenous lipids via de novo production of phosphatidic acid, which ultimately activates both mTOR complexes – mTORC1 and mTORC2. Activated mTORC2 phosphorylates the survival kinase Akt at Ser 473 which is required for full Akt activation. A direct substrate of Akt and a major …

Analyzing Conformational Changes In The Binding Of Hiv-1 Matrix Protein, N And C Terminals, To Calmodulin, Nousha Karimi, Fabian Valdez, Davis Mau, K. Sakamaki

Student Scholar Symposium Abstracts and Posters

Worldwide, more than 38 million people are living with human immunodeficiency virus (HIV), about 84 million people have become infected with HIV since the start of the epidemic, and 40.1 million of those diagnoses led to death. HIV Type-1 is the most common type of HIV, attacking the body’s immune system by destroying CD4 cells. The virus attaches itself to the CD4 cell, taking control of its DNA and replicating itself to release more HIV into the bloodstream. The Gag proteins of HIV-1 are crucial players in the virus’ assembly, release, and maturation; it utilizes its essential matrix protein (MA) …

Studying The Phosphorylation Of Isocitrate Dehydrogenase In Humans, Hannah Smith

Chemistry & Biochemistry Undergraduate Honors Theses

Isocitrate dehydrogenase is an important enzyme in the citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. While there are three isoforms of isocitrate dehydrogenase (IDH1, IDH2, and IDH3), this research will focus on IDH1. The phosphorylation of isocitrate dehydrogenase is a process that has been linked to the formation of both luminal-like and basal-like breast cancer. Despite these correlations, the mechanisms that cause breast cancer development are unknown. To examine this, an enzyme activity assay for each phosphorylation variant and crystallization were conducted. The results of these indicate that phosphorylation at each site (IDH1-T77, IDH1-S188, …

Review Of Biomedical Applications Of Cardiovascular Tissue Engineering, Natalie M. Howard

Honors College Theses

Tissue engineering can be defined as processes that aim to generate three-dimensional functional tissues in vitrothat have been favorably altered according to the structural, biochemical, electrophysiological, and biomechanical properties of the desired tissue before implantation into the human body. In relation to cardiac tissues, these properties would include the ability to conduct action potentials, withstand systolic pressure, permit sufficient O₂ and CO₂penetration, sufficient vascularization to supply nutrients for cellular activity, surface topology that enables cellular communication, and more. As heart diseases and instances of myocardial infarction continue to rise worldwide, there is an increasing need for …

Rational Design, Synthesis And Biology Of Immunostimulatory Peptides, Nelson Casanova

Seton Hall University Dissertations and Theses (ETDs)

This dissertation reports the design, synthesis, characterization, and biological studies of three uniquely structured peptides, derived from ubiquitinated multiple myeloma proteins and ubiquitinated B7H6 ligand. The peptides were made into linear or branched shapes, with the branched peptides containing both major histocompatibility complex (MHC) class two and NKp30 binding motifs properties in one peptide. This results in an immunocytotoxic response (via cytokines and chemokines) of both natural killer cells and cytotoxic T lymphocytes (CTLs). These shapes were determined for data comparison but also to increase cytokine proliferation, the shapes help with healthy cell aviation. Thus, the linear monomer (contains a …

Nicotinamide Riboside And Beta-Hydroxybutyrate Activate Parallel Pathways For C. Elegans Lifespan Extension, Mckenzie Peters

Undergraduate Honors Theses

Supplementation with nicotinamide riboside (NR), a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide (NAD⁺) extends lifespan in the nematode C. elegans and delays aging-related pathologies in mammals. During aging, levels of NAD⁺ decline causing metabolic dysfunction and oxidative damage. Studies in C. elegans found that when NR was administered during larval development it induced the mitochondrial unfolded protein response (UPR^mt), which is frequently associated with lifespan extension. Both calorie restriction (CR) and ketogenic diets (KD) have been shown to extend lifespan, in part through increasing NAD⁺ and through increasing levels …

Mitochondrial Roles In Developmentally Programmed Heart Disease, Eli John Louwagie

Dissertations and Theses

Offspring of diabetic and obese mothers (ODOM) have greater risks of heart disease at birth and later in life. However, prevention is hindered because underlying mechanisms are poorly understood. Mounting studies in the Developmental Origins of Health and Disease field suggest that mitochondria play key roles in developmentally programmed heart disease similar to the roles they play in cardiomyopathy in adults with diabetes and obesity. However, whether mitochondria are responsible for the short[1]and long-term cardiac disease seen in ODOM remains unknown. Here, we sought to delineate the roles of mitochondria in the hearts of ODOM, determine whether mitochondria are playing …

The Role Of Sars-Cov-2 Orf8 Protein Arks Motif On Novobiocin Binding, Si Chun Chiu, My T. Nguyen

Celebrating Scholarship and Creativity Day (2018-)

The discovery of the SARS-CoV-2 virus during the COVID-19 pandemic required scientists to develop medical solutions to reduce infectivity, severity of symptoms, and death. Although vaccines and drugs provided urgent assistance, the need to continue developing better drugs is necessary long term, and understanding the structure of the virus and finding potential inhibitors would prove vital to discovering solutions to this worldwide health problem. This experimental project focuses on targeting the unique accessory protein, Open Reading Frame 8 (ORF8) in SARS-CoV-2 through studying its interactions with a repurposable drug, novobiocin. Importantly, ORF8 specializes in helping evade immune system checks by …

Toward The Design, Synthesis, And Characterization Of Abiotic Coiled-Coil Peptides Via Solid-Phase Copper-Catalyzed Azide-Alkyne Cycloaddition (Sp-Cuaac) Click Reaction For The Preparation Of Controlled Self-Assembly Molecular Building Block, Liaquat Ali

Chemistry Theses

The production of cutting-edge materials, the development of novel medications, drug delivery systems, technological advancements, and biosynthesizing all depend on molecular building blocks. Proteins are required for the creation of intricate, well-organized structures, and coiled-coil protein domains are vital subunits for the oligomerization of protein complexes, gene expression, and the structural components of biological materials. The numerous interactions between a wide variety of amino acids make it difficult to assemble protein complexes with a particular shape. In the current study, we successfully designed and synthesized four different 32-residue peptides, each of which had two modified amino azide residues. These peptides …

Apoptosis Induction In Jurkat T-Lymphocytes By Proton Pump Inhibitors (Ppis), Shreya Murali, Randall Reif

Student Research Submissions

Apoptosis, commonly known as programmed cell death, constantly occurs in humans. As a cancer cell increases in acidity, apoptosis is induced. In healthy cells, proton pump proteins allow for H⁺ ions to permeate cellular membranes, regulating pH. However, proton pump inhibitors (PPIs), such as omeprazole, prevent proton movement. In previous studies, omeprazole induced cell death in Jurkat T lymphocytes; however, there was no confirmation of whether the cells died through apoptosis, or through necrosis, where the cell bursts. By using Annexin-V staining, the effects of omeprazole, dexlansoprazole, and esomeprazole on apoptosis induction can be measured. Cell death was observed …

From Deep Mutational Mapping Of Allosteric Protein Landscapes To Deep Learning Of Allostery And Hidden Allosteric Sites: Zooming In On “Allosteric Intersection” Of Biochemical And Big Data Approaches, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The recent advances in artificial intelligence (AI) and machine learning have driven the design of new expert systems and automated workflows that are able to model complex chemical and biological phenomena. In recent years, machine learning approaches have been developed and actively deployed to facilitate computational and experimental studies of protein dynamics and allosteric mechanisms. In this review, we discuss in detail new developments along two major directions of allosteric research through the lens of data-intensive biochemical approaches and AI-based computational methods. Despite considerable progress in applications of AI methods for protein structure and dynamics studies, the intersection between allosteric …

Assessment Of Histone Acetyltransferase Homologs In Cryptococcus Neoformans, Phoebe Bridy, Felice Kho, Yuqi Wang

Liberty University Research Week

Undergraduate

Basic

Study Of Protein Extraction Techniques For M. Foliorum Phages, Lola Sibaud, Anna Elgersma

Student Academic Conference

Characterizing phages is becoming increasingly important in biochemistry and biotechnology due to their potential to treat bacterial infections without need for antibiotics. Last year, students attempted to isolate proteins from Microbacterium foliorum infecting phages Babydotz and Rosadiaz. Proteins were successfully extracted; however, after further analysis it was shown that the obtained proteins belonged to the host bacteria and not the phages. The purpose of this study was to find a method to separate phage from host bacterial debris to successfully isolate phage proteins and analyze them later. Isolating phage proteins could help us characterize more phages and know more about …

Novel Plant Peroxidase Investigation For Use In Various Biochemical And Practical Applications, Sally Hess

Liberty University Research Week

Undergraduate

Basic

Activation Of Nrf2 Pathway By Natural Products, Genesis Schat, Madelyn Sedlachek

Liberty University Research Week

Undergraduate

Basic

A Fisher Indole Synthesis Approach To Phidianidine Analogues, Anna Tingler, Trinity Ghering, Samuel Ross

Undergraduate Research Competition

Naturally occurring products are molecules that are found in the natural world without the aid of humans. Aspirin and opium are famous examples of this classification of molecule. Another example of natural products that are less known are the phidianidines. Phidianidines A & B were isolated from a shell-less mollusk, Phidiana militaris. These molecules are comprised of a 1,2,4-oxadiazole ring, an indole and an aminoalkylguanadio group. These compounds have exhibited striking pharmacological behavior such as that of neutralizing reactive oxygen species and acting as an agonist for the μ-opioid receptor. In recent years, the synthesis of phidianidine analogues has replaced …

A New Approach To The Core Of Flinderole C, Ana Pettijohn, Claire Romain

Undergraduate Research Competition

The flinderoles A-C are a class of anti-malaria bisindole alkaloids from plants of the Flindersia genus. Flinderole C was specifically from the Papua New Guinean plant called F. amboinensis and is the most potent antimalarial of the group. Malaria is a parasitic infectious disease usually found in the hot, tropic regions of the world, such as parts of Africa. It is estimated that nearly half the world's population lives in an area where it is endemic. Furthermore, malaria was estimated to have caused over 600,000 deaths in 2020. While measures to limit the spread of the disease lessen its impact, …

Environmental Bacteriophage Presence In The Drainage Ponds At Coastal Carolina University, Alexei Chesnutwood

Undergraduate Research Competition

The purpose of this research is to detect naturally occurring, lytic bacteriophages and identify the environmental factors that influence their presence on Coastal Carolina University’s campus. Bacteriophages are non-living viruses that only infect bacteria, and these viruses are found in abundance in every environment. Likewise, coliphages are viruses that exclusively infect coliform bacteria. Eleven treated and untreated freshwater sample sites were chosen for weekly sampling on CCU’s campus. During water sample collection, ambient environmental conditions were measured. In addition, precipitation was tracked over the collection period as runoff relates to the proliferation of bacteriophages. If plaque assays indicated the presence …

Developing A Safe And Effective Papillomavirus Screen To Be Used On College Students, Nicole Frantz

Undergraduate Research Competition

Human papillomavirus (HPV) is the most common sexually transmitted infection that accounts for approximately 5% of all cancers worldwide and affects more than 80 million people in the US alone, according to the CDC and National Cancer Institute. Human papillomaviruses are small, nonenveloped, icosahedral DNA viruses that infect squamous epithelial cells. The viral particles consist of a single double stranded DNA molecule bound to histones and contained within a protein capsid composed of structural proteins late (L)1 and L2. To date, over 100 different genotypes of HPV have been identified, and approximately 15 types are considered oncogenic in cervical, vulvar, …

Analysis Of Attitudinal Student Learning Benefits From A Course-Based Undergraduate Research Experience (Cure) Adapted For Online Format, Ambika Kapil, Luis C. Gonzalez Isoba, Niraj Pathak, Arthur Sikora, Santanu De

FDLA Journal

Course-based Undergraduate Research Experiences (CUREs) are an increasingly utilized model for exposing students to research. The lack of robust assessments is a major hurdle to wider adoption of CUREs. The Coronavirus Infectious Disease 2019 (COVID-19) pandemic necessitated a drastic shift of in-person courses to the online format. Using the Participant Perception Indicator (PPI) survey, we measured students’ self-reported changes in learning from such a biochemistry course at a large university in south Florida based on the Biochemistry Authentic Scientific Inquiry Lab (BASIL) model. By doing this, we were able to better understand the student-benefits of CUREs and how these benefits …