Biochemistry Commons^™

Investigation Of Oncogenic Ras And Endoplasmic Reticulum-Mitochondria Calcium Flux And Their Relationship In The Context Of Tumorigenesis, Emma Anderson

Senior Honors Theses

Intracellular calcium as a signaling molecule is a pervasive feature of cellular pathways, especially those that manage internal homeostasis and transitions through the cell cycle, so much so that regulated, responsive calcium flux between the endoplasmic reticulum (ER) and the mitochondria has been suggested to play a major role in cancer development. Another factor commonly implicated in tumorigenesis is RAS, an oncogene that controls signaling for many pathways that are also regulated by calcium. While both calcium and oncogenic RAS signaling are implicated in cancer development, possible links between them have yet to be determined. The identification of these links …

Synthesis Of Alpha Domain Of Metallothionein For Hydrogen Production, Aditya Surakanti

Honors Theses

The world relies on nonrenewable resources for a significant portion of its usable energy, the most common being fossil fuels. Fossil fuels release many unwanted byproducts during their extractions and conversion processes. As a result, this excessive use leads to harsh consequences upon the environment, including rapid global warming, release of numerous water and air pollutants, and it could possibly lead to an increased risk of death in those who are exposed to these toxins. In response to this scenario, the goal of my project is to design an artificial hydrogen catalyst, which can absorb sunlight and oxidize H2O into …

1st Place Contest Entry: Designing Hollow Nanogels For Drug Delivery Applications, Mo Hijazi

Kevin and Tam Ross Undergraduate Research Prize

This is Mo Hijazi's submission for the 2022 Kevin and Tam Ross Undergraduate Research Prize, which won first place. It contains their essay on using library resources, their bibliography, and a summary of their research project on hollow-core nanogels.

Mo is a second-year student at Chapman University, majoring in Biological Sciences. Their faculty mentor is Dr. Molla Islam.

Structural And Biochemical Studies On Disease Associated Proteins: Heat Shock Protein 60 And Hiv Capsid, Alejandro Rodriguez

Open Access Theses & Dissertations

Structural studies on proteins provide valuable knowledge, from information about their fundamental nature, to laying a foundation for rational drug design. Here, we study two proteins, a human mitochondrial chaperonin heat shock protein 60 (Hsp60) and the main structural HIV-1 protein capsid (CA). We focus on the structural nature of both proteins to try to understand their role in disease and elucidate the mechanism of potential drug treatments. Hsp60 is a chaperonin found in human mitochondria that is responsible for assisting client proteins reach their native, functional, state. The mechanism by which it catalyzes protein folding, however, has not been …

Prefusion Spike Protein Conformational Changes Are Slower In Sars-Cov-2 Than In Sars-Cov-1, Vivek Govind Kumar, Dylan S. Ogden, Ugochi H. Isu, Adithya Polasa, James Losey, Mahmoud Moradi

Chemistry & Biochemistry Faculty Publications and Presentations

Within the last 2 decades, severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) have caused two major outbreaks; yet, for reasons not fully understood, the coronavirus disease 2019 pandemic caused by SARS-CoV-2 has been significantly more widespread than the 2003 SARS epidemic caused by SARS-CoV-1, despite striking similarities between these two viruses. The SARS-CoV-1 and SARSCoV-2 spike proteins, both of which bind to host cell angiotensin-converting enzyme 2, have been implied to be a potential source of their differential transmissibility. However, the mechanistic details of prefusion spike protein binding to angiotensin-converting enzyme 2 remain elusive at the …

Observing Reactive Events At The Aqueous Graphene Oxide Interface Using Deep Neural Network Potentials, Lukas Kim

Honors Capstones

No abstract provided.

Datadescription-Detection Of Sulfur Dioxide By Broadband Cavity-Enhanced Absorption Spectroscopy (Bbceas), Ryan Thalman, Nitish Bhardwaj, Callum Flowerday, Jaron C. Hansen

ScholarsArchive Data

Files archived include the following:

Figure1.txt This file contains all the data used to make Figure 1 in the paper.

Figure4.txt This file contains all the data used to make Figure 4 in the paper.

Figure5.txt This file contains all the data used to make Figure 5 in the paper.

Figure6.txt This file contains all the data used to make Figure 6 in the paper.

Figure7.txt This file contains the code, written in Igor, that was used to generate this figure.

Figure8.txt This file contains all the data used to make Figure 8 in the paper.

Figure9.txt This file contains …

Glypro As A Self-Immolative Spacer For The Release Of Payloads From Antibody-Drug Conjugates, Justin Michael Howe

Undergraduate Honors Theses

Antibody-drug conjugates (ADCs) are an increasingly popular modality for targeted drug delivery in many oncological and immunological applications. The paratope of a monoclonal antibody (mAb) directs the delivery of a conjugated therapeutic payload to antigen expressing cells, resulting in a controlled transport of payload to a desired cell type. Internalization of the ADC followed by lysosomal degradation results in the release of a payload to perform its biochemical function. A chemical linker between the drug and the antibody is responsible for the stability of the conjugate in circulation alongside mediating the release of an unmodified payload under lysosomal conditions. Currently, …

The Development Of Inhibitors For Sars-Cov-2 Orf8, My Thanh Thao Nguyen

CSB and SJU Distinguished Thesis

An unexpected outbreak of SARS-CoV-2 caused a worldwide pandemic in 2020. Many repurposed drugs were tested, but there are currently only three FDA approved antivirals (Merck’s antiviral Molnupiravir, Pfizer’s antiviral Paxlovid, and Remdisivir).1 Most of the antiviral drugs tested SARS-CoV-2 main protease and RNA-dependent RNA polymerase. However, it is important to explore different drug targets of SARS-CoV-2 to prepare for the virus mutations of the future. This research looks at an alternative approach in which SARSCoV- 2 Open Reading Frame 8 (ORF8), which has been shown to be a rapidly evolving hypervariable gene, was chosen to be the protein of …

Sars-Cov-2 Main Protease Inhibitors Repurposed For Hiv-1 Protease Binding, Jacob Minkkinen

CSB and SJU Distinguished Thesis

Severe acute respiratory syndrome (SARS-CoV-2) led to the COVID-19 global pandemic, with over 460 million cases of infection and over 6 million deaths since the start of the pandemic. SARS-CoV-2 is a retrovirus that utilizes a main protease (Mpro). Mpro is a catalytic cys/his protease. Several treatments were proposed to stop the pandemic including repurposing drugs to inhibit the Mpro. Another retrovirus that uses a protease is human immunodeficiency virus (HIV-1) which has been a global epidemic for 40 years and is a devastating disease that attacks the immune system. HIV-1 has infected 79.5 million people and has killed an …

Microplastics, The Environment, And Reproductive Health: How Is The Accumulation Of Microplastics In Our Environment And Bodies Impacting Reproductive Health?, Katherine Hayward

Independent Study Project (ISP) Collection

As global trends in both production and consumption of plastics continue to evolve, the bioaccumulation and biomagnification of microplastic particles in our everyday lives follow suit. This increasingly relevant problem has only recently been explored in the context of global health, and more specifically, reproductive health. Along with this steady increase in plastics and our exposure to them, researchers have separately observed adverse patterns in reproductive health. The chemicals involved throughout the microplastic life cycle may be playing a key role in these simultaneous patterns. With the aid of previous studies and publications on microplastics, exposure pathways, endocrine disruptors, and …

Investigating The Role Of Fun30, A Chromatin Remodeler, In Dna Repair, Mehwish Iqbal

Dissertations

The repair of DNA double-strand breaks (DSBs) is crucial for maintaining genome stability. DSB repair needs to take place within the complex organization of the chromatin, and this requires changes in the chromatin structure adjacent to DSB sites. These changes occur through covalent histone modifications that alter histone-DNA contacts as well as by the action of ATP-dependent chromatin remodelers. Many chromatin remodelers, including Fun30, are involved in DSB repair. Fun30 facilitates DNA end resection at DSB site during the homologous recombination repair pathway. Apart from its role in DNA repair, Fun30 promotes gene silencing at heterochromatic loci such as telomeres, …

Attempted Synthesis & Antibacterial Properties Of Apt-6k Against Ndm-1 K. Pneumoniae, Alec Bofetiado

Honors Theses

NDM-1 K. pneumoniae is a highly resistant bacterial organism that is capable of causing debilitating nosocomial infections in immunocompromised patients. Only "last-resort" antibiotics--such as colistin--work against this organism. Therefore, new antibiotics are needed to help fight against these types of infections. APT-6K is a novel compound that was demonstrated to be effective against MRSA with nanomolar concentrations in a prior study. Novel methods of APT-6K synthesis and its testing for antibiotic effects against NDM-1 K. pneumoniae were attempted in this research. APT-6K synthesis was unsuccessful. Commercially-prepared APT-6K also did not demonstrate growth inhibition against NDM-1 K. pneumoniae nor against a …

Efforts To Increase The Ketamine-Like Activity Of The Rapid-Acting Antidepressant Ro-25-6981 (Mi-4) By Increasing Ampa Potentiation, Nathan Heger

Annual Research Symposium

The small molecule ketamine has generated much interest due to its rapid antidepressant effects. Despite having a rapid onset, ketamine has poor bioavailability, short duration of action, toxicities with long-term use, and a high potential for abuse. The molecule MI-4 (RO 25-6981) has also been shown to have both a rapid and sustained antidepressant effect. Most of the research into the mechanism of the rapid onset of MI-4 and ketamine has focused on their interaction with the NMDA receptor in addition to some monoamine transporters. Some recent publications have shown a significant role of AMPA receptors in the ketamine antidepressant …

Case 71: Lactate Dehydrogenase As A Therapeutic Target To Treat Parasitic Disease, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

In this case study, researchers use their knowledge of lactate dehydrogenase in parasites and humans to investigate inhibitors that are selective for the parasite agent.

Endogenous Cftr Expression In Human Epithelial Cell Lines, Zithlaly Amezquita

Undergraduate Research Conference

CFTR (Cystic Fibrosis Transmembrane-conductance Regulator) is a plasma membrane protein that functions as a chloride ion channel on many epithelial cells. There are over 1000 mutations that affect the function of this protein; however, the most common mutation is DF508. CFTR mutations target many secretory organs like pancreas and lungs causing the genetic disease cystic fibrosis (CF), common among Caucasians of northern European origin. Detection of endogenous CFTR expression is possible by a difficult and costly immunoprecipitation method but not by the most used western blotting method. Therefore, the goal of this project was to detect the endogenous CFTR expression …

Analyzing Inhibitors Of The Sars-Cov-2 Endoribonuclease Nsp15, Mary Staunton

Honors Scholar Theses

The global pandemic caused by the virus SARS-CoV-2 has devastated the world. A flurry of research into the structures and activities of the virus have identified several viable targets for drug therapy, including the endoribonuclease nsp15, also known as EndoU. EndoU has been shown to play a role in diminishing the host cell’s immune response to the virus by cleaving signaling dsRNA, specifically targeting uridine sequences. The development of the crystal structure nsp15 allowed our lab along with others to perform virtual screenings to identify inhibitors that might be able to dock at the active site and inhibit the activity …

Amelioration Of Cr (Vi) Into Cr (Iii) By Some Heavy Metal Resistant Bacterial Strains Isolated From Naran Valley, Ifrah Fayyaz, Asma Kalsoom, Rida Batool

Journal of Bioresource Management

Total thirty-two strains were isolated from both water and soil samples collected from Naran Valley which is surrounded by the rugged mountains, located in the province of Khyber Pakhtunkhwa, Pakistan. Streak plate method was used to screen the bacterial strains for resistance against selected heavy metals like chromium (Cr), cobalt (Co), copper (Cu), nickel (Ni) and zinc (Zn). Resistance against multiple heavy metals was shown by all the strains, but S15 and W15 were significant as they exhibited a maximum resistance to chromium and copper (1200 µg/ml). These strains also presented multiple antibiotic (ampicillin, tetracycline, chloramphenicol, and erythromycin) resistance patterns. …

Inhibition Of Nuclear Transport Of Perilipin 5, Hope Lewis

Undergraduate Honors Thesis Projects

Obesity, type II diabetes mellitus, and non-alcoholic fatty liver disease are all conditions related to aberrant lipid storage in humans. Nearly all cells have the capacity to store neutral lipids in lipid storage droplets, organelles that regulate the storage of their hydrophobic contents. All lipid storage droplets are coated with at least one member of the perilipin family of proteins. Perilipin 5 is expressed in oxidative tissues including oxidative muscleand fasted liver and has been shown to play important roles in neutral lipid metabolism in these tissues. Perilipin 5’s involvement in gene expression was discovered during catecholamine-stimulated lipolysis, where the …

Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing …