Biochemistry Commons^™

Mxene-Enabled Wearable Biosensors: A Design Framework For Autonomous Biosensing, Jegan Rajendran, Gymama Slaughter

Center for Bioelectronics Publications

MXenes, a rapidly expanding family of two-dimensional transition metal carbides and nitrides, have emerged as leading materials for wearable bioelectronics due to their metallic conductivity, termination-rich surfaces, mechanical compliance, and tunable interlayer structures. However, wearable biosensor performance does not arise from conductivity alone, but from coupled interactions among surface termination chemistry, heterointerface engineering, hierarchical architecture, and device integration under dynamic physiological conditions. This review establishes a predictive structure-interface-device framework linking MXene chemistry to system-level performance across electrochemical, mechanical, gas, optical, and energy-storage modalities. We analyze how termination-controlled adsorption governs charge transfer and selectivity, how heterojunction formation modulates carrier density and …

Potential Environmental Triggers Of Goodpasture's Disease And The Role Of The Sulfimine Crosslink, Colton S. Miller, Andrea Florian, Elena Pokidysheva

SPARK Symposium Presentations

Goodpasture’s syndrome (GP) is an autoimmune disorder that primarily affects kidneys and lungs. The main issue for patients with Goodpasture's syndrome is the binding of autoantibodies to the glomerular basement membrane (GBM), which hinders the filtration of blood. A key characteristic of Goodpasture's syndrome is the presence of autoantibodies that target the NC1 domain of the α345 isoform of type IV collagen, a crucial component of the GBM that provides structural support and is critical for filtration function. Sulfilimine bonds crosslink the collagen IV NC1 hexamers, contributing to the stabilization of these structures. A recent clinical case of recurring Goodpasture's …

Comparing The Differences Of Hsp90Α And Hsp90Β In Native Protein Complex Incorporation, Daryna Serediuk

Honors Theses and Capstones

Epichaperomes are long-lasting, stable assemblies of chaperones, co-chaperones, and associated factors that facilitate cell survival in maladaptive cellular states. Their inhibition has emerged as an attractive therapeutic strategy for the treatment of cancer and neurodegenerative diseases (Rodina et al., 2016). Epichaperomes are hallmarks of robust proliferation in cancer cell populations across many cancer types and are abundantly present in several stem cell varieties, including induced pluripotent stem cells, human embryonic kidney cells, and cancer stem cells (Kishinevsky et al., 2018).

The core protein of the eukaryotic heat shock protein machinery, Heat Shock Protein 90 (Hsp90), is a central chaperone that …

Generating Concentrated Ring Polymers Through Supercoiled And Open Circle Pdna Isoform Separation, Kelsey E. Hodsdon

Honors Theses and Capstones

DNA can serve as a model polymer due to its high uniformity compared to synthetic polymers. Plasmid DNA (pDNA) in particular offers a well-defined, low-dispersity model for studying topologically uniform systems of a cyclic nature. pDNA has unique isoforms known as open circle (OC) and supercoiled (SC). Using fast protein liquid chromatography (FPLC), specifically anion exchange chromatography (AEX), these OC and SC isoforms can be separated in order to access their unique material properties. Our lab was able to yield the pure SC isoform. However, OC isoform separation has been more challenging. Various difficulties arose during this process, including imaging …

Mitochondria As Primary Cause Of Neurodegeneration: Evaluating Causality Across Amyotrophic Lateral Sclerosis (Als), Alzheimer's, And Parkinson’S Diseases, Makenzie G. Johnson

Undergraduate Honors Theses

Neurodegenerative diseases like Alzheimer's Disease (AD), Parkinson’s Disease (PD) and Amyotrophic Lateral Sclerosis (ALS) have historically been explained through alternate hypotheses despite shared clinical hallmarks that lead to neuron loss. However, these varying explanations could not account for how disease onset begins among other individual issues. This thesis aims to show that mitochondrial dysfunction is a primary driver of neurodegeneration as well as a unifying mechanism shared between the three diseases. Evidence presented in this thesis will show that many issues can arise in mitochondria including issues with energy production, mitochondrial DNA (mtDNA), apoptosis activation, and calcium regulation. These issues …

Effects Of Rnai Of Ribophorin 1, Eukaryotic Translation Initiation Factor 2 Beta, And Peptidylprolyl Isomerase A In Acyrthosiphon Pisum, Brandon L. Kennemer

Master's Theses or Doctor of Nursing Practice

Three genes found in the Unfolded protein response, Ribophorin 1, Eukaryotic translation initiation factor 2 beta, and Peptidylprolyl isomerase A are thought to be potential targets for RNA Interference (RNAi) in Acyrthosiphon pisum.  Ribophorin 1 (RPN1) is a transmembrane glycoprotein that assists in anchoring ribosomes to the rough endoplasmic reticulum membrane.  It acts as a substrate-specific chaperone.  It facilitates N-glycosylation by delivering newly synthesized proteins to the oligosaccharyltransferase (OST) complex.  Eukaryotic translation initiation factor 2 beta (eIF2B) is a key component of the eIF2 heterotrimer that facilitates protein synthesis initiation by binding GTP and recruiting a specific transfer RNA to …

Characterization Of Phytoplankton-Excreted Metabolites Mediating Carbon Flux Through The Surface Ocean, Yuting Zhu, Hanna S. Anderson, Eli Salcedo, Samuel E. Miller, Krista Longnecker, Melissa C. Kido Soule, Sheean T. Haley, Gretchen J. Swarr, Rogier Braakman, Sonya T. Dyhrman, Elizabeth B. Kujawinski

Chemistry & Biochemistry Faculty Publications

The marine labile dissolved organic carbon (DOC) pool is a dynamic reservoir of thousands of molecules that cycles approximately one-quarter of Earth’s primary production within days to weeks. After excretion by phytoplankton and other microbes, metabolites are rapidly consumed, resulting in low standing concentrations (picomolar to low nanomolar). Despite the decades-long search for labile DOC sources and molecular identities, marine phytoplankton exometabolomes are not well characterized, largely due to difficulties in measuring small polar molecules in saline water. Here, we profiled the exometabolomes of six axenic phytoplankton species representing key functional groups including a diatom (Thalassiosira pseudonana CCMP1335), a …

Design And Advancement Of Analytical Frameworks For In Vivo Single-Photon Calcium Imaging To Characterize Temporal- And Treatment-Dependent Neural Adaptations To Opioid Exposure And Withdrawal In The Medial Prefrontal Cortex, Alexia R. Alsum Dr.

Theses and Dissertations--Pharmacy

Despite the availability of several approved medications for opioid use disorder (OUD), it remains a significant public health concern characterized by persistent neurobiological adaptations that drive relapse and impede successful recovery. The medial prefrontal cortex (mPFC), a region critical for executive control and decision-making, undergoes pronounced functional changes during chronic opioid exposure and withdrawal, yet the cellular mechanisms underlying these adaptations remain poorly understood. This dissertation aims to investigate longitudinal alterations in mPFC neural activity across opioid exposure and withdrawal using in vivo single-photon calcium imaging and newly developed computational frameworks.

Following standard preprocessing to extract and normalize calcium traces, …

Exploring The Limitations Of Substrate Scope In Dimethylallyltryptophan Synthases, Evan T. Miller

Theses and Dissertations--Pharmacy

Natural products (NPs), are the largest source of bioactive compounds in Nature, and are essential to the treatment of human disease. Nearly 50% of drugs approved for use from 1981 to 2019 owe some aspect of their development to NPs, either in terms of their structure, pharmacophore, or mechanism of action. However, NPs are difficult to structurally optimize. Chemoenzymatic methods for NP derivatization have been increasingly seen as practical alternatives to traditional synthetic methods. Prenyltransferases (PTs) are involved in the primary and secondary metabolism of plants, bacteria, and fungi, and they are key enzymes in the biosynthesis of many clinically …

Exploring Fructose Mimetics As Chemotherapeutic Potentiators: Impact On Glut5-Mediated Cancer Cell Vulnerability, Vedant Buwa

Dissertations, Master's Theses and Master's Reports

Metabolic reprogramming toward increased sugar uptake is a hallmark of cancer, and fructose-specific uptake through the facilitative transporter GLUT5 is selectively upregulated in several adenocarcinomas, including breast and lung cancer. This dissertation develops and characterizes a panel of fluorescent fructose mimetics – the coumarin-based ManCou probes and the quinolinone-based ManQuin probes – as GLUT5-targeted reporters, cytotoxic effectors, and chemosensitization adjuvants, and establishes the boundaries within which each role holds.

The central experimental strategy pairs each GLUT5-targeted glycoconjugate with its sugar-free aglycone control, isolating transporter-mediated cytotoxicity from cytotoxicity intrinsic to the fluorophore itself. In luminal (MCF7) and triple-negative (MDA-MB-231) breast carcinoma, …

Seeing Through The Fuzz: Understanding Conformational Diversity In The Fuzzy Coat Of Amyloids Across Fibril Polymorphs Using Solid-State Nmr, Carah K. Allen

Scripps Senior Theses

The aggregation of α-synuclein (α-syn) into amyloid fibrils is a central pathological hallmark of Parkinson’s disease and other related synucleinopathies. Although monomeric α-syn is intrinsically disordered, the protein assembles into multiple fibril polymorphs that differ in their β-sheet core structures. Surrounding each polymorph is the “fuzzy coat,” which is a highly dynamic, intrinsically disordered region (IDR) that is not resolved by high-resolution structural techniques, such as Cryo-EM, but is thought to influence fibril interactions, propagation, and toxicity. Understanding whether different polymorphs maintain distinct fuzzy-coat conformational ensembles is therefore essential for connecting amyloid structure to biological function. To address this question, …

Structural Determination And Regulatory Mechanisms Of Rice Lipoxygenase-1, Lillie Ballanco, Nathaniel Gilbert, Adam Offenbacher

Distinguished Undergraduate Researcher Program

Lipoxygenases (LOXs) are non-heme iron containing enzymes that catalyze the oxygenation of polyunsaturated fatty acids (PUFAs) such as linoleic acid (LA). These lipoxygenase enzymes are found in both plants and animals. In humans, LOXs have been linked to inflammatory diseases such as asthma, atheroscelerosis, and allergic rhinitis. Plant LOXs have been primarily linked to the growth, development, and stress response of the plant. This paper focuses on Oryza sativa lipoxygenase-1 (OsLOX1), an enzyme found in rice (Oryza sativa). OsLOX1 has been associated with enhanced drought tolerance in rice and may play a role in regulating growth under water-limited conditions. Understanding …

N-Allylation Of Secondary Amides With Unsymmetrical Propionates, Remi Graff

Honors Theses

The combination of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and Et3N promotes the N-allylation of 4-methoxyacetanilide 2 with unsymmetrical propionates 1 (eq 1). The amide substrate is believed to undergo conversion to a nucleophilic silyl imidate in the presence of TMSOTf and the amine base, which concurrently promotes carbocation formation in the same flask through the loss of trimethylsilyl propionate, leading to N-allylation of the amide. A range of unsymmetrical propionates, accessed by varying the R and R’ substituents, react efficiently in this one-pot process with yields ranging from 44% to 99%, affording regioselective ratios of up to >20:1 through formation of regioisomers …

Development Of A Python Pipeline For The Inference Of Selection In Human Genomes And Applications To Adh1b*2, Aine Macdermott

Honors Theses

Human evolutionary genomics provides an avenue to understand how genetic variation has been impacted by the environmental pressures of the past, revealing how selective pressures impacted past populations and contributed to present-day biological diversity. In this thesis, I describe the construction of a Python-based computational pipeline designed to automate and integrate multiple analyses of positive selection across worldwide population datasets, including derived allele frequency calculation, haplotype-based tests of selection, RELATE-based genealogical inference, and CLUES2-based temporal modeling. By automating file preparation, format conversion, job submission, result aggregation, model comparison, and visualization, this pipeline streamlines the data interpretation process, and shifts focus …

Exploring Phosphoregulation Of Myo3a Using Quantitative Fluorescence Image Analysis In Cos7 Cells, Vu Hao Minh Nguyen Phan

Honors Theses

Myosin 3A (MYO3A) is an unconventional myosin involved in the formation and maintenance of hair-cell stereocilia of the sensory epithelia in the inner ear. The kinase domain has been implicated in phosphoregulation of MYO3A activity through intermolecular autophosphorylation. Previous studies using mass spectrometry identified two potential phosphorylation sites in the motor domain. To investigate the regulatory roles of these sites, we generated glutamic acid point mutations in our mchr-MYO3AΔK construct to mimic phosphorylation and assayed the constructs for their ability to tip-localize and influence filopodial density via transfection into COS7 cells. The phosphomimic constructs were less able to generate filopodia …

An Investigation Into The Potential Role Of Thioester Bonds In Prebiotic Atp Synthesis, Adam J. Ruf

Williams Honors College, Honors Research Projects

In this project I will attempt to show a potential prebiotic pathway for the synthesis of ATP. This pathway involves the use of thioester bond containing molecules, as derivatives of these bonds have been shown to exhibit enzyme-like catalytic properties. Nuclear magnetic resonance spectroscopy will be utilized to characterize each step of the pathway to ensure it is successful.

C. Difficile Detection Method For First Responder Glove Application, Alli N. Senedak

Williams Honors College, Honors Research Projects

Clostridioides Difficile (C. diff) is a Anaerobic Gram-positive bacillus that is capable of spore formation, making it difficult to control its spread and duration in clinical environments. This phenomenon can provide danger to first responders, healthcare workers, and patients. The goal of this project is to create a biosensor capable of detecting C. diff in a clinical setting that can be applied to a glove apparatus. The project will involve the use of C. diff aptamers activated on the surface of an electrode. Once surface activation has been verified via surface analysis, the electrodes will be exposed to C. diff …

Multicomponent Deoxyribozyme Probes For Targeted Detection Of Cancer Associated Gene Insertions, Samuel R. Veleke

Honors Undergraduate Theses

Insertions and deletions (indels) in DNA sequences of genes are linked with cancers such as glioblastoma (GB). Thus, indels may be used as potential cancer biomarkers. In the NANOG gene, its pseudogene NANOGP8 has a 22 base pair insertion sequence for GB patients. In this work, the NANOG gene and the insertion sequence were detected in one sample using a dual-fluorescent assay containing two multicomponent split deoxyribozyme (Dz) probe complexes. One complex used TXR fluorescence to detect the gene regardless of the insertion’s presence. The other complex used fluorescein (FAM) fluorophore to detect the insertion. The probes were able to …

Bio-Orthogonal Chemistry-Based Strategy To Turn-On And Turn-Off Crispr-Cas9 Gene Editing In Solution And In Live Cells, Bhoomika Pandit

Electronic Theses & Dissertations (2024 - present)

The CRISPR–Cas9 system is a widely popular tool for genome engineering. There is a strong interest in developing tools for temporal control of CRISPR-Cas9 activity to address some of the challenges and to broaden the scope of potential applications. In this thesis I describe two biorthogonal based approaches to either Turn-ON and Turn-OFF CRISPR-Cas9 gene editing.

In first project work I describe a bio-orthogonal chemistry-based approach to Turn-ON Cas9 nuclease activity with temporal precision. We report a TCO-acylimidazole reagent that acylates 2′-OH groups of RNA. Poly-acylation (“cloaking”) of RNA was optimized in vitro using a model 18-nt oligonucleotide, as well …

Disrupted Circadian Rhythms Affect Hallmark Pathologies In Alzheimer’S Disease-Related Mouse Models, Valeria Buzinova

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s Disease (AD) is a complex neurodegenerative disease with two hallmark pathologies: extracellular amyloid-b (Ab) and intracellular neurofibrillary tangles (NFTs). Ab is proteolytically processed from amyloid precursor protein (APP) by b-secretase and g-secretase as a monomeric peptide prone to aggregation. Eventually, the aggregate-prone monomers will form dense plaques that are difficult to break down and remove. These plaques begin to deposit into the cortex decades prior to the formation of NFTs and the onset of cognitive decline. NFTs are comprised of hyper-phosphorylated tau. Tau is a protein that serves to promote and stabilize the formation of microtubules. The formation of …