Structural Biology Commons^™

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 …

Systematics Of Disk-Winged Bats (Thyroptera), Courtney L. Klumpp

Capstone Showcase

This thesis investigates the evolutionary relationships among disk-winged bats in the genus Thyroptera, a small group of Neotropical bats known for the adhesive suction disks on their wings and feet that allow them to roost inside tightly rolled leaves. The distinctive morphology and behavior of these bats have not been extensively documented, and their phylogenetic relationships remain only partially resolved. The goal of this research is to better understand how these species are related to one another and to determine whether the five recognized species of Thyroptera form a single monophyletic group. To address this question, morphological and genetic …

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, …

Potency Dependent Angiogenic Effect Of Bellis Perennis On In Ovo Chick Chorioallantoic Membrane Assay, Jayanthdevan V, Winston Vargheese V, Anish Fathima K, Lohita S

Indian Journal of Research in Homoeopathy

Background: Hormesis is the biological response of an organism for a particular dosage of a substance. The lower dose stimulates and higher dose inhibits. J Compton Burnett, an eminent homeopath, prescribed Bellis perennis for breast and uterine tumours, which suggests it could be due to the antiangiogenic property or angiogenic inhibiting property and clinically also it is used for healing of fractured bone and wound healing which may be due to angiogenic promoting property. This experiment deals with the dose dependent effect of Bellis perennis on In Ovo Chick Chorioallantoic Membrane Assay. Objective: To evaluate the Hormesis effect of Bellis …

Structural Basis Of A Class Ii Ribonucleotide Reductase Found If Mycobacterium Tuberculosis, Leah Jacob

Student Scholar Symposium

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading global health challenge, particularly due to its ability to enter a dormant, drug-tolerant state that enables long-term persistence within the host. Just before dormancy, Mtb replicates its entire genome creating DNA precursors for when the infection reactivates. Ribonucleotide reductases (RNRs) play a critical role in bacterial survival by catalyzing the conversion of ribonucleotides into deoxyribonucleotides, a necessary step for DNA replication and repair. The class II RNR, NrdZ, has been implicated in facilitating Mtb persistence under hypoxic stress conditions, yet its structural and mechanistic function remains largely uncharacterized. …

Context Dependent Regulation Of Dicer Function During Oocyte-To-Embryo Transition, Nick A. Newkirk

Dissertations and Theses (Open Access)

Over two decades ago, Dicer was discovered as the primary enzyme responsible for the generation of small RNAs known as the microRNAs (miRNAs) and short interfering RNAs (siRNAs). Spatiotemporal regulation of Dicer-dependent small-RNA biogenesis affects many aspects of biology, including aging, disease progression, fertility, and cancer. Interestingly, a distinct population of Dicer-dependent small RNAs, known as the endogenous siRNAs (endo-siRNAs), are uniquely abundant in the germ cells and gametes, and are critical for normal fertility. Despite their function regulating new life, the mechanisms controlling their biogenesis and subsequent germ cell functions remain poorly defined. Work to parse these mechanisms in …

From Sequence To Allostery: How Amino Acid Differences Rewire Coupled Conformational Heterogeneity In The Ptp Enzyme Family, Shivani Sharma

Dissertations, Theses, and Capstone Projects

Protein Tyrosine Phosphatases (PTPs) are critical regulators of cellular signaling, and their activity is often modulated through allosteric mechanisms. Allostery is defined as a chemical or conformational change in one site of the protein due to a binding event at another site. Although several studies have investigated aspects of allostery in PTPs, the mechanistic foundations underlying allosteric regulation remain poorly understood. Despite a highly conserved catalytic domain across PTPs, regions with low or no conservation suggest potential "rewiring" of allosteric networks. This raises key questions about the universality versus individuality of allosteric mechanisms across the PTP family.

In this work, …

Role Of Nucleic Acids As Chaperones In Protein Folding, Zijue Huang

Electronic Theses and Dissertations

Many proteins have slow folding times in vitro that are physiologically untenable. To combat this challenge, ATP-dependent chaperonins are thought to possess the unique ability to catalyze protein folding. Performing quantitative model selection using protein folding and unfolding data, we here show that short nucleic acids containing Gquadruplex (G4) structure can also catalyze protein folding. Performing the experiments as a function of temperature demonstrates that the G4 reshapes the underlying driving forces of protein folding. To understand the structural basis of this catalytic activity, we introduce NMR method to solve the structures, at base-level resolution, of a multiconformer G4 with …

Claudin-1-Mediated Signaling And Therapy Resistance In Colorectal Cancer: From Mechanism To Translation, Mark W. Primeaux

Theses & Dissertations

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with metastatic cases showing poor response to chemotherapy due to both intrinsic and acquired therapy resistance. Claudin-1 (CLDN1), a tight junction protein, is overexpressed and mislocalized outside of tight junctions in CRC, where it contributes to an aggressive, metastatic phenotype. Although this causal relationship has been well established, the mechanisms by which CLDN1 promotes tumor progression were unclear due to its lack of intrinsic enzymatic activity. This dissertation investigates the molecular mechanisms through which CLDN1 drives oncogenic signaling, its role in therapy resistance, and its translational potential as both a …

Development Of A Cure In Principles Of Cell And Molecular Biology, Heather Seitz

Sabbatical Projects

This project presentation highlights the work done during sabbatical to develop an authentic research experience into BIOL135 Principles of Cell and Molecular Biology. The sabbatical allowed for development time but further work was done to measure impact and outcomes for future implementation.

Unwrapping The Cube Visual Essay, Arthur L. Loeb, C. Todd Stewart

Loeb Design Science: Documents

A visual and conceptual essay illustrating the many faces and properties of the cube.

Structural Functional Investigation Of Hap40, Amanda M. Solbach

Dissertations and Theses (Open Access)

STRUCTURAL FUNCTIONAL INVESTIGATION OF HAP40

Amanda Marie Solbach

Dissertation Advisor: Sheng Zhang, Ph.D.

Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene, resulting in a mutant huntingtin (mHTT) protein with an elongated polyglutamine tract. While the genetic basis of HD is well established, the mechanisms underlying mHTT toxicity and its impact on cellular function remain incompletely understood. Recent discoveries implicate Huntingtin-associated protein 40 (HAP40) as a critical regulator of HTT stability and intracellular function. However, the physiological and pathological significance of this interaction has not been fully explored.

This …

Design And Evaluation Of An Innovative Biomimetic Coral Transport Container, John-Christopher L. Calulo, Wilfredo Y. Licuanan, Leah D. Madrazo, Dana Isabelle P. Villano, Angel Nicole B. Villanueva

Sinaya: A Philippine Journal for Senior High School Teachers and Students

Coral reefs are vulnerable to disruptive human activities such as pollution, overfishing, and coastal development—degrading water quality and reef structures. Active reef restoration entails temporarily relocating several corals to aquaculture facilities to achieve successful rehabilitation; however, current coral transport methods pose certain risks, such as stress-induced mortality, which can result from physical damage during transportation. Existing studies on coral transport have explored various techniques for collecting, shipping, and maintaining live coral specimens. The design consists of petal-shaped areas where the waves gather, akin to a coral reef’s grooves, separated by wedges—the spurs—that cause waves to divide. The different design modifications …

Elucidating The Roles Of Eukaryotic Initiation Factors Involved In Dap5 Mediated Translation, Jacob Nk Quartey

Dissertations, Theses, and Capstone Projects

Translation initiation in eukaryotes is a highly regulated process essential for accurate protein synthesis. It is a dynamic process that involves a complex interplay between messenger RNAs (mRNAs), ribosomal subunits, and a host of initiation factors, ensuring precise start codon selection and the subsequent assembly of the translation machinery. This process has well been known to be mediated by the eukaryotic Initiation Factor (eIF4F), which consists of the cap binding protein eIF4E, the scaffolding protein eIF4GI, and the helicase factor eIF4A.The recognition and binding of eIF4E to the m⁷G cap structure of the mRNA is essential for the …

Biophysical Analysis Of S100a12 And The Nucleosome Core Particle, Christopher Diforte Jr.

Dissertations, Theses, and Capstone Projects

Calcium signaling and chromatin remodeling are fundamental regulatory processes that control protein activity and gene expression, respectively. This thesis investigates the molecular mechanisms by which local ligand binding and structural perturbations propagate allosteric effects across larger protein systems, using two distinct yet mechanistically analogous models: the calcium binding protein S100A12 and the nucleosome core particle. These studies are unified by a shared emphasis on how physical forces govern biological function.

In the first part, we explore calcium mediated allostery in S100A12, focusing on the distinct roles of its two EF-hand calcium binding loops (EF-I and EF-II). Through a combination of …

Kinetic Analysis Reveals T6a-Protein Specificity For T6a And Hn6a Trna Modifications, Cassandra Mae Harker

University Honors Theses

Transfer RNA (tRNA) is essential for accurate translation of genetic information and plays a role in cellular processes such as lipid aminoacylation and bacterial conjugation. Base modifications help tRNA fold correctly and function properly. An important base modification, N6-threonylcarbamoyladenosine (t6A) occurs at position A37 in the anticodon-stem-loop of tRNA. This modification is crucial for decoding ANN codons. Interestingly, an Archeal organism, Methanocaldococcus jannaschii, can have either t6A and hydroxynorvalylcarbamoyl-6- adenosine (hn6A) modification at the same position on tRNAs. As Tsa proteins catalyze the formation of both t6A and hn6A modifications, this raises the question of whether discrimination between these …

Structural Studies Towards The Mechanism Of Scanning And Initiator Trna Recruitment During Eukaryotic Translation Initiation, Da Cui

Dissertations, Theses, and Capstone Projects

The central dogma, proposed by Francis Crick in 1958, marks the direction of the flow of genetic information: from DNA to DNA (DNA replication), DNA to RNA (transcription), and RNA to protein (translation). Each of these is tightly regulated and important for cells and organisms to function correctly, grow, and reproduce.

In the eukaryotic system, the initiation stage of translation is the first, the rate-limiting, and the most regulated stage. It involves direct regulation of multiple eukaryotic initiation factors (eIFs), scanning factors such as DHX29, and other factors such as Poly-A binding protein (PABP). It starts with the small subunit …

Fire Fossils: Biomineral Infrastructures In Untangling Climates, Tanmayee More

Masters Theses

Diatoms drift, sediments sink, wildfires generate their own weather. Lightning strikes can blast sand into glass, and microscopic organisms do the same in the cold recesses of the ocean. What alchemies and metabolisms catalyze space, time, and energy? What are the thermodynamics of infrastructure in Climate Change?

Places, materials, and beings are afterimages. Through alchemical experiments, and multi-scalar imaging, I develop simulations of wildfires, and their profound, reverberating effects. In this thesis, a glass-meets-landscape experimental process enters these obscured conditions and renders new material relations for the built environment.

Tree Story, Jia Hu

Masters Theses

What is Nature?

Nature is a system of intelligence. It means designing for efficiency—often by learning from strategies that have evolved over time. In my research, I use patterns to interpret and decode nature.

To explore nature, I began with the red cedar tree, aiming to simulate and predict its growth patterns—forms shaped by both internal biology and external forces. By analyzing its geometry, I sought to understand how trees embody the dynamic relationship between organism and environment. These patterns reveal the adaptive logic of life.

Patterns are central to understanding nature. While tree geometry may appear chaotic, it follows …

Characterization Of Sars-Cov-2 Replication And Transcription Complexes Via Structural And Evolutionary Approaches, Amelie Ghirardo, Ben Shabatian, Avishai Aghelian, Kyle Tau, Eleonora Gianti

Undergraduate Research

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused around 700M cases and over 7M COVID-19-related deaths recorded worldwide (World Health Organization, March 2025). Aiming to effectively combat this and other disease-causing Coronaviruses (CoV), unprecedented research efforts led to the development of new vaccines and antiviral therapies. Due to emergence of variants of concern (VOCs) with increased transmissibility, immune evasion from vaccination, and potential to resist the available treatments, SARS-CoV-2 continues to represent a major threat to global health. Hence, there is a pressing need to discover new antivirals with broad-spectrum efficacy against multiple SARS-CoV-2 variants and related CoVs. This project …