Chemistry Commons^™

The Development Of Individualized Anemia Treatments Using Point Of Care Diagnostics To Distinguish Anemia Caused By Infection Or Chronic Inflammation, Dr. Richard Watt

Journal of Undergraduate Research

Background: Anemia that accompanies inflammation is associated with negative outcomes for patients. Early intervention to treat anemia is an important step in improving the quality of life for anemic patients. Our lab proposed to develop simple diagnostic tests using a Lateral Flow Immunoassays (LFIs) to measure the presence of a hormone called hepcidin because hepcidin is the master regulator of iron homeostasis in the body and elevated hepcidin levels lead to anemia.

Rational Design Of Multifunctional Enzyme-Like Catalysts For Assembly-Line Chemical Synthesis, David Michaelis

Journal of Undergraduate Research

The main objectives of this proposal was to publish our preliminary findings in peptide catalysis and then submit applications for external funding. Both of these objectives were accomplished during the grant period. In the Fall of 2017, we published our first paper on the development of our new enzyme-like catalysts (ACS Catal. 2017, 7, 7704–7708). This publication should serve as a springboard for additional publications in the area (on which we are currently working) and help ensure external funding for this project. During 2017-2018, we submitted 3 grant applications to the NIH to help support this project. These submissions have …

Modeling Main Group Metal Alkane Functionalization Reactions In Highly Acidic Carboxylic And Sulfuric Acid Solvents, Lily H. Carlson, Daniel H. Ess

Journal of Undergraduate Research

Our group is interested in identifying the unknown mechanisms of main-group C-H functionalization reactions. In the long term, our goal is to use computational chemistry tools to develop general principles on mechanisms, intermediates, reactivity, and selectivity for hydrocarbon C-H functionalization reactions by p-block main-group compounds as well as provide prediction of new catalysts and reactions. However, in providing these predictions, it remains unclear if different mechanistic pathways and intermediates will be predicted if examined in a complete solvent sphere (see Figure 1 for technical details). This is especially important for non-aqueous solvents such as carboxylic acids and sulfuric acid. To …

Heterodinuclear Co-Zr Compound Shows Increased Reactivity In Kumada Coupling, James Coombs, Daniel Ess

Journal of Undergraduate Research

Heterodinuclear compounds containing a metal–metal bond represent a potentially useful subclass of catalyst in organic synthesis. Heterodinuclear compounds offer the possibility of increased reactivity due to interactions between metal centers (Scheme 1A). These so-called cooperative effects can enhance reactivity by changing the electronic density, increasing nucleophilicity/electrophilicity of the reactive metal, and by lowering the energy barriers for changes in oxidation state. These changes in reactivity can allow a heterodinuclear compound to be an effective catalyst for many chemical reactions that would be unfeasible with a mononuclear analogue.

Cyclic Peptide Catalyst Design, Millicent Campbell, David Michaelis

Journal of Undergraduate Research

Enzymes found in nature are more efficient catalysts than those used in organic chemistry labs. However, natural enzymes are not ideal for organic synthesis because they only make one product and only work in specific conditions. The Michaelis lab designed a catalyst capable of mimicking enzyme-like reactivity in the lab. This catalyst consists of an alpha helix with an imidazolidinone catalyst and a thiourea catalyst (see figure 1). The imidazolidinone catalyst and thiourea catalysts are attached adjacent to each other on the alpha helix, which acts as a rigid scaffold that can mimic the proximity effects seen in natural enzymes. …

Function Of Ric-8a In G Protein E+- Subunit Biogenesis, Barry Willardson

Journal of Undergraduate Research

1. Grant Ludlam. The MEG award helped support Grant’s work from January 2015 through August 2016. During this time Grant has worked on three projects. He investigated the role of Ric8A in the folding of the G protein a subunit and its assembly into the G protein heterotrimeric complex. Unfortunately, his results showed that deletion of Ric8A in the photoreceptor cells of mice did not affect G protein signaling. As a result, he changed his research focus to determining the structure of the BBSome core complex. He assisted a graduate student, Takuma Aoba, in this work. They used a combination of …

Mentoring Undergraduates At The Intersection Of Organic Synthesis And Peptide Science, Steven L. Castle

Journal of Undergraduate Research

Our academic goals were threefold. First, we aimed to synthesize building blocks and begin assembling them to construct the anticancer peptide yaku’amide A (YA, Figure 1). Our purposes in synthesizing YA were to develop new chemical reactions suitable for efficiently preparing its unusual amino acids (shown in red and blue in Figure 1), and synthesize simplified analogues for use in studies designed to reveal its biological target and mode of action. Our second academic goal was derived from the first and involved investigating the ability of bulky dehydroamino acids (i.e., the amino acids of YA shown in blue in Figure …

Alzheimer’S Disease: A New Model Defining The Mechanism Of Iron- Catalyzed Radical Damage To Neurons, Richard Watt, Jonathan Wisco

Journal of Undergraduate Research

The MEG proposal focused on understanding how elevated homocysteine levels cause the inability of cells to control iron levels as a cause for Alzheimer’s disease. Iron is associated with the amyloid plaques and tau tangles that are proposed to cause damage to neurons. Dr. Wisco and I previously submitted an NIH R15 proposal that was viewed positively but was not funded due to a lack of preliminary data. Our goal was to use MEG funding to provide preliminary data supporting the hypothesis. We proposed that Homocysteine was a dangerous trigger for disrupting iron metabolism. Biochemical techniques, immunohistochemistry techniques and MRI …

Nanomaterials Used To Destroy Water Contaminants, Roger Harrison

Journal of Undergraduate Research

1. Evaluation of how well the academic objectives of the proposal were met

Students working in the mentoring environment synthesized nanomaterials composed of ZnO and characterized the materials by SEM, TEM, XRD, and IR. They then used the materials as efficient photocatalysts to destroy dyes. They applied reactions and knowledge they had learned in their chemistry courses. They learned to solve problems by finding new ways to synthesize or characterize their compounds. They learned to run, fix, and change settings on multifaceted instruments. They learned to trouble-shoot problems to solve instrumental errors. They learned to reduce human error and understand …

Organic Synthesis As A Platform For Mentoring Undergraduates, Steven L. Castle

Journal of Undergraduate Research

This report summarizes the results that were generated under the auspices of the mentoring environment in my laboratory from January 2014 to the present. A total of six undergraduates participated in the mentoring environment during this period. Their names and accomplishments are listed below.

Mechanism Of Assembly Of The Bardet-Biedel Syndrome (Bbs) Complex, Barry M. Willardson

Journal of Undergraduate Research

1. Devon Blake. Devon was the most productive student I have had in my 18 years at BYU. The MEG award helped support his work from January 2013 through May 2014. During this time, Devon co-authored two papers on the effects of cell-type specific deletion of phosducinlike protein 1 (PhLP1) in rod and cone photoreceptor cells (Lai et al. (2013) J. Neurosci. 33, 7941-7951, selected by the Faculty of 1000 as a high-impact paper and Tracy et al. (2014) PLOS One in press). He reported this work in poster form at an international meeting of the Federation of American Society …

Extent And Mechanism Of Translational Readthrough In Humans, Michael Porter, Dr. John Prince

Journal of Undergraduate Research

Introduction Proteins are an integral part of the cell. They are responsible for metabolism, DNA replication, transportation, and responding to changes in environment. Because of their importance to the cell, proteins are often drug targets due to the important roles they play in carrying out cellular function. Proteins are made by ribosomes which are responsible for translating proteins from mRNA. The end of translation is signaled by a stop codon in the RNA. However, in some organisms such as viruses and yeast, the stop codon may be bypassed in an event known as translational readthrough.

Microbial Pretreatment Of Waste For Anaerobic Digestion, Braden Myers, Jaron Hansen

Journal of Undergraduate Research

This project will demonstrate the technical feasibility of microbial pretreatment of lignocellulose for enhanced production of biogas when coupled with secondary anaerobic digestion as well as optimize the entire process.

Learning Chemistry Through Experimentation, Brent Kamba `, Dr. Jennifer Nielson

Journal of Undergraduate Research

There is a great need for students to learn scientific skills in Uganda. Very few students pass the national chemistry exams (about 40%) and even fewer go on to study science fields in higher education. The teaching methods in Uganda are a little bit old fashion where students often just learn facts and practise rote memorization. Rarely do they develop the critical and analytical skills to help them succeed in science jobs. Teachers also express that the curriculum is very theoretical, and not experimental.

Mitochondrial Membrane Lipids Regulator In B-Cll Leukemia Research, Brooke Keeton, Dr. John Prince

Journal of Undergraduate Research

B-cell chronic lymphocytic leukemia (B-CLL) is the most common type of leukemia in adults.1 Over 75% of patients diagnosed with B-CLL are over the age of 50 years old, and have a median survival between 18 months and 3 years.2 B-CLL originates from a mutation in the DNA of white blood cells, the potent infection fighters of the body. This genetic mutation produces abnormal white blood cells, rendering them nonfunctional and resulting in a weak immune system. While this mutation originally occurs in the bone marrow, it slowly invades other parts of the body, including the lymph nodes, liver, and …

Mega-Autophagosome Induction By Human Cox-3 And Human Nucleobindin, Gideon N. Logan, Daniel Simmons

Journal of Undergraduate Research

Cyclooxygenase (COX) isoenzymes catalyze the first step of prostanoid synthesis, which plays a role in various conditions including pain, inflammation, arthritis, and cancer. Recently our laboratory has shown that mammalian cell lines transfected with the COX-1 splice variant, COX-3, express translationally recoded proteins, including four unglycosylated lower molecular weight forms, 57kDa (57 rcCOX-3), 50kDa (50 rcCOX-3), 47kDa (47 rcCOX-3) and 44kDa (44 rcCOX-3.)

Bottom-Up Development Of Nanoelectronics Using Dna Origami Templates, John Jensen, Dr. Adam T. Woolley

Journal of Undergraduate Research

Introduction DNA origami is the method of folding a large single stranded DNA (ssDNA) with multiple smaller ssDNA “staple” strands into a predesigned shape, making it an attractive option in the bottom-up construction of nanoelectronic components, such as nanowires. These structures can be used as templates for placement of conductive species1, such as gold nanoparticles (Au NPs). In order to attach Au NPs to the structure, polyadenine (polyA) tails are added to ends of certain staple strands, allowing attachment of Au NP “seeds” that are functionalized with a thiolated polythymine (polyT) sequence. After attachment, the Au NP seeds are connected …

Molecular-Level Interactions Responsible For Retention In Liquid Chromatography, Jessica Jenkins, James Patterson

Journal of Undergraduate Research

Introduction In many fields of work, such as medicine or pharmaceutical research, it is necessary to separate chemically similar compounds. Liquid chromatography, which involves a mixture of compounds (analyte) dissolved in a mobile phase flowing through a packed column (stationary phase), is the most widely used chemical separation technique. Changes in operational parameters such as the mobile or stationary phase composition, temperature, pressure, pH, etc. affect retention time Operational parameters are currently chosen by trial-and-error because we understand very little about the molecular interactions between the analyte and the mobile phase/stationary phase interface. Specifically, it is unclear how enthalpy and …

Optimizing Metallization Of Dna-Templated Nanostructures, Andrew Dearden, Adam Woolley

Journal of Undergraduate Research

With countless technologies that rely on microprocessors, there is a great need for increasingly smaller microelectronic components. Traditionally, manufacturers have employed a “top-down” approach to build microelectronics – that is, they have attempted to scale functional microcircuitry components down in size, hoping for similar performance in a smaller circuit. This top-down approach is expensive, often costing manufacturers hundreds of dollars per part. A much more cost-effective approach to microelectronics has emerged over the past decade in the field of molecular science: that is, to develop circuitry from the “bottom-up” using macromolecules such as deoxyribonucleic acid (DNA). Scientists have now devised …

Supramolecular Chemistry For Undergraduate Students, David V. Dearden, Roger G. Harrison

Journal of Undergraduate Research

The goal of this proposal was to train graduate and undergraduate students through research experiences in supramolecular chemistry in a multi-group environment. Academically, our objective was to synthesize and characterize new supramolecular host molecules and to develop applications for these molecules. We believe we have been quite successful, as demonstrated by the presentations and publications listed below and as shown by the receipt of a National Science Foundation grant by one of the teams involved in this research, in a year when such grants were particularly difficult to obtain.

Byu Meg Report, Emily Bates

Journal of Undergraduate Research

The academic objectives were met by the proposal. Students learned to sequence DNA and to interpret the sequence to know if there was a rare genetic change occurring in the sequence that they interpreted. Students learned to write academic abstracts, introductions, results, and conclusions in the format of an academic journal. Furthermore, together the students determined that the genetic change in a family with an inherited syndrome of birth defects was not one that had previously been identified or described.

Mentoring Undergraduates Via Organic Synthesis, Steven L. Castle

Journal of Undergraduate Research

This report summarizes the results that were generated under the auspices of the mentoring environment in my laboratory from January 2013 to the present. A total of eight undergraduates participated in the mentoring environment during this period.

Autophagy-Mediated Mechanisms Of Chemoresistance In Cancer, David Broadbent, Dr. Joshua Andersen

Journal of Undergraduate Research

The resistance of tumor cells to chemotherapy is a critical problem in the clinic and is a common cause of mortality in cancer. Emerging data suggests that resistance to chemotherapy is caused by a tumor-expressed protein called 14-3-3ζ, yet the mechanism to explain 14-3-3ζ-mediated chemoresistance is not completely understood (1). Rapid growing tumors often outgrow their blood supply resulting in regions of hypoxia (low glucose and oxygen). These cells must adapt or die and those that do adapt often become metastatic and chemoresistant. A recently proposed mechanism by which cancer cells are able to adapt to hypoxia is via autophagy, …

Organocatalytic Aryl−Aryl Bond Formation: An Atroposelective [3,3]‑Rearrangement Approach To Binam Derivatives, Gong-Qiang Li, Hongyin Gao, Craig Keene, Michael Devonas, Daniel H. Ess, LaśZlóKüRti *

Journal of Undergraduate Research

Herein we disclose an organocatalytic aryl− aryl bond-forming process for the regio- and atropo- selective synthesis of 2,2′-diamino-1,1′-binaphthalenes (BINAMs). In the presence of catalytic amounts of axially chiral phosphoric acids, achiral N,N′-binaphthyl hydrazines undergo a facile [3,3]-sigmatropic rearrangement to afford enantiomerically enriched BINAM derivatives in good to excellent yield. This transformation represents the first

example of a metal-free, catalytic C(sp²)−C(sp²) bond

formation between two aromatic rings with concomitant de novo atroposelective installation of an axis of chirality. Density functional calculations reveal that, in the transition state for C−C bond formation, the phosphoric acid proton of …

Kir2.1 Effects On Craniofacial And Limb Development In Knockout Mice, Joy Williams, Dr. Emily Bates

Journal of Undergraduate Research

Birth defects arise because of both genetic and environmental factors. Children with genetic alteration of the inwardly-rectifying potassium ion channel Kir2.1 channel have heart arrhythmias, impaired cognitive function, and facial and limb abnormalities. Children that suffer from Fetal Alcohol Syndrome have cognitive and social development problems, heart defects, and facial abnormalities—including small eyes, small head, small upper jaw, and a small upper lip1. Kir2.1 is bound and blocked by alcohol2 and thus we predicted that it is the molecular target of Fetal Alcohol Syndrome. We designed experiments to determine how Kir2.1 is required during development and found that within 14 …

The Use Of Alpha-1-Antitrypsin (Aat) In The Downregulation Of Nuclear Factor Kappa-Light-Chain-Enhancer Of Activated B Cells (Nf-Κb) As A Treatment For Acquired Immunodeficiency Syndrome (Aids), Aaron Mcbride, Dr. Gregory F. Burton

Journal of Undergraduate Research

Current Human Immunodeficiency Virus (HIV) treatment is greatly hindered due to viral reservoirs throughout the body prolonging and perpetuating infection.i Large stores of HIV exist in the follicular dendritic cell (FDC) microenvironment, located primarily in the lymph nodes and spleen. Free-floating virus has a half-life of less than two hours; however, FDC-trapped virus has a half-life of over eight weeks and can be rescued in its infectious state longer than nine months after the initial infection,ii showing the role of FDCs as an HIV reservoir.iii Studies in the Gregory Burton laboratory focus on the interactions between HIV, FDCs, and CD4+ …

Structure Of The Phlp1-Gβ-Cct Complex Reveals A Molecular Mechanism For Gprotein Β Subunit Folding And Βγ Dimer Assembly, Devon Blake, Dr. Barry Willardson

Journal of Undergraduate Research

Cells detect and respond to a myriad of extracellular signals via seven-transmembrane G protein-coupled receptors and their associated G protein signaling pathways. The pathway is initiated by the binding of a signaling molecule, such as a hormone or neurotransmitter, to its binding site on the extracellular side of the receptor. This interaction activates the G protein heterotrimer, composed of Gβ, Gβ, and Gβ subunits, which functions by propagating the signal throughout the cell. First, however, the G protein heterotrimer must be assembled from its nascent polypeptides. The initial step in this process is the formation of the Gβγ dimer. Gβγ …

Splicing Of Chicken Cyclooxygenase-2, Matthew Lelegren

Journal of Undergraduate Research

As described in the proposal, my goal was to further understand the mechanisms of mRNA processing of the chicken gene called Cyclooxygenase (COX)-2. There are many mechanisms by which mRNA molecules are modified in order to produce proteins that fulfill the needs of a given cell. The mechanism I chose to study was called alternative splicing, a process through which sequences are removed from the mRNA thereby altering the structure and function of the protein to be translated from its sequence. In brief summary splicing mechanisms, the cells possess machinery that recognize certain sequences, called splice sites, as a guide …

Estrogen Signaling In Migraine Pathogenesis, Sarah Bahr, Dr. Emily Bates

Journal of Undergraduate Research

Migraine is a disorder that can include aura, headache, nausea, and hypersensitivity to all sensory modalities. It affects over thirty million people in the US. Migraines affect men and women equally until puberty, but overall migraines affect 3x more women than men. They also increase in frequency and severity during periods of estrogen fluctuation and often subside after menopause. Moreover, hormone supplements and birth control can affect migraine patterns. These correlations of migraine episodes to the menstrual cycle and increased pain sensitivity in response to estrogen suggest that differences in estrogen signaling contribute to migraine. We hypothesized that estrogen receptor …

Acetylation Of Sod1 As A Regulator Of The Tumor Stress Response, Matthew Whited, Dr. Joshua L. Andersen

Journal of Undergraduate Research

In cancer patients, a lack of cell apoptosis (programmed cell death) coupled with increased levels of cell proliferation leads to the formation of a tumor. Among the available treatment options, cytotoxic chemotherapy is the most common. The primary purpose of this treatment is to induce tumor cell apoptosis. In many cases, tumor cells develop chemoresistance, rendering chemotherapy ineffective as a method to activate apoptosis. Understanding the mechanisms that lead to chemoresistance is a critical step toward developing methods to increase the effectiveness of chemotherapy treatments.