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Articles 1 - 30 of 47
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Bptf-Dependent Regulation Of Vaccine-Induced B Cell Responses, Alexandria Sturtz
Bptf-Dependent Regulation Of Vaccine-Induced B Cell Responses, Alexandria Sturtz
Arts & Sciences Graduate Student Theses and Dissertations
Vaccination is a method of safely generating highly specific, long-lived immunological memory that can protect a host upon future exposures to a pathogen. Memory B cells (MBCs) and high-affinity plasma cells (PCs) are pivotal populations generated during vaccine-induced immune responses as they provide rapid secondary immune responses upon antigen re-exposure. MBCs and PCs can both be produced by germinal centers (GCs), which are microanatomical structures where B cells undergo iterative rounds of somatic hypermutation and affinity-based selection. Regulation of the GC is complex and the network of factors that controls the identity, function, and magnitude of the GC B cell …
2d-Nanosilicate Carriers For Sustained Delivery Of Vaccine Components, Chih Yun Liu
2d-Nanosilicate Carriers For Sustained Delivery Of Vaccine Components, Chih Yun Liu
McKelvey School of Engineering Graduate Student Theses & Dissertations
Laponite® 2D Nanosilicates (NS) are disc-shaped platelets (~30 nm diameter, ~1 nm thick) with positively charged edges and negatively charged faces, capable of loading proteins, drugs, and nucleic acids via electrostatic interactions to form a house-of-cards gel that sequesters cargo. Here, we evaluated NS for sustained delivery of antigens and Toll-like receptor (TLR) agonists to extend germinal center duration and enhance antibody quality. The model antigen ovalbumin (OVA) was adsorbed onto NS at acidic pH in a ~1:1 ratio, with partial unfolding that remained stable at physiological pH. NS-OVA complexes were efficiently internalized by dendritic cells, with uptake driven primarily …
Computational And Mathematical Modeling Of Microbial Community And Host Responses To Microbiota-Directed Complementary Foods Administered To Children With Acute Malnutrition., Steven J. Hartman
Arts & Sciences Graduate Student Theses and Dissertations
Globally, millions of children suffer from undernutrition, with stunting affecting 150 million and wasting nearly 50 million under five years old. Current interventions have shown limited effectiveness in mitigating long-term consequences such as stunted growth, cognitive deficits, and immune dysfunction. Through this body of work, I investigated the efficacy of a microbiota- directed complementary food (MDCF-2) as a next generation therapeutic food to combat childhood stunting. Across two randomized controlled trials involving Bangladeshi children with either moderate acute malnutrition or post-severe acute malnutrition, MDCF-2 significantly outperformed standard ready-to-use supplementary foods (RUSF), leading to significantly improved ponderal and sustained linear growth …
Biology Department Publications: 2018, Sam Lindgren
Biology Department Publications: 2018, Sam Lindgren
Biology Department Bibliographies
This document is a noncomprehensive list of publications made by graduate students, post-doctoral researchers, and faculty members in the Biology Department in 2018. It indexes those publications available through major databases, and serves as an archival record of the Department’s robust scholarly contributions.
Synthesis Of Addressable Libraries: New Lessons And The Need For Proper Characterization For Microelectrode Array-Based Reactions, Albert Huang
Arts & Sciences Graduate Student Theses and Dissertations
The Moeller group has been developing synthetic tools for building molecular libraries on microelectrode arrays since 2004. Such a library is intriguing because one can take advantage of the library for biological signaling studies. Microelectrode arrays can serve as a powerful platform for those experiments since every electrode in the array can be addressed individually. Unique members of the library targeting biological receptors that one is interested in can be restricted only above unique electrodes in an array. Thus, high-affinity ligands for those receptors can be identified with this strategy. To make this method work, one has to make sure …
Elucidating The First Protective Mutation From Inherited Alzheimer’S Disease - Apolipoprotein E3 Christchurch (Apoe3ch) And Insights Into Apoe Ligand-Receptor Interactions, Yun Chen
Arts & Sciences Graduate Student Theses and Dissertations
Alzheimer’s disease (AD) is the major cause of dementia. An inherited form of AD (dominant inherited AD) starts much earlier in life, often in the fourth and fifth decade. A recent case report described an individual who was resistant to dominantly inherited AD caused by a PSEN1-E280A mutation and was a homozygous carrier of the APOE3 Christchurch (APOE3ch) variant. A clear separation between amyloid and tau pathology occurred in this unique AD case. However, whether APOE3ch contributed to the protective effect remains unclear. In this thesis, we generated a humanized APOE3ch knock-in mouse and crossed it to an amyloid-β (Aβ) …
Neuroepigenetic Mechanisms Of Brain Development: From Technology To Biological Insights, Allen Yen
Neuroepigenetic Mechanisms Of Brain Development: From Technology To Biological Insights, Allen Yen
Arts & Sciences Graduate Student Theses and Dissertations
Each cell in the brain has the same genomic sequence, yet they can have vastly different phenotypes and function. This diversity is a result of complex genetic and signaling pathways, and knowing how these are regulated is key to understanding physiological development and how pathogenic dysfunctions arise. Genomic methods such as chromatin immunoprecipitation followed by sequencing (ChIP-seq) and assay for transposase-accessible chromatin with sequencing (ATAC-seq) have played pivotal roles in dissecting these processes. However, a key limitation is that the cells are destroyed upon observation of their molecular states, which preclude our ability to correlate historical epigenetic information with future …
Mechanisms Of Kcnq1-Calmodulin Channel Complex Activation To Dual Open States, Po Wei Kang
Mechanisms Of Kcnq1-Calmodulin Channel Complex Activation To Dual Open States, Po Wei Kang
McKelvey School of Engineering Graduate Student Theses & Dissertations
Voltage-gated potassium channels (KV) facilitate cellular excitability essential for cardiac contraction and neuronal spiking. In response to changes in the membrane potential, KV channels conduct transmembrane K+ flux to terminate action potentials. Myriad drugs target KV channels to achieve therapeutic goals such as anti-arrhythmic and anti-convulsant effects. Owing to their physiological significance, KV channels are exquisitely regulated by a cohort of auxiliary proteins and signaling molecules. The KCNQ1 or KV7.1 voltage-gated potassium channel stands out as an archetype in this regard. Modulators such as the KCNE subunit family, membrane lipid PIP2, and calmodulin (CaM) enable KCNQ1 to conduct phenotypically distinct …
Optogenetic Heart Pacing And Heart Arrest In Drosophila Melanogaster Using Integrated Ocm Imaging And Light Stimulation System, Yuxuan Wang
McKelvey School of Engineering Graduate Student Theses & Dissertations
Optogenetics has been widely applied to cardiovascular research using different models. Among them, Drosophila melanogaster (fruit fly) outstands for its similarity of human genes for disease modeling and short life cycle for rapid screening to analyze genetic mechanisms of heart disease. However, most of the current models only allow either activation or inhibition of the heartbeat, which is not sufficient to model complex arrhythmia. Our lab developed a novel Drosophila transgenic model based on a double transgenic line containing two light-sensitive genes, Channelrhodopsin-2 (ChR2) and Halorhodopsin2.0 (NpHR2.0), that enable dual-directional control of the heartbeat rhythm. Real-time optical control of the …
Advancing The Portability, Field Of View, And Spatiotemporal Resolution Of Multi-Parametric Photoacoustic Microscopy, Fenghe Zhong
Advancing The Portability, Field Of View, And Spatiotemporal Resolution Of Multi-Parametric Photoacoustic Microscopy, Fenghe Zhong
McKelvey School of Engineering Graduate Student Theses & Dissertations
Capable of structural, functional, molecular, and metabolic imaging with high spatial resolution in vivo, photoacoustic microscopy (PAM) is an emerging tool in biomedical research. Further, recent advances in multi-parametric acquisition and analysis make PAM uniquely capable of simultaneously mapping the total concentration of hemoglobin (CHb), oxygen saturation of hemoglobin (sO2), and blood flow speed. However, there are multiple major limitations, including, the large footprint, low imaging speed, limited imaging contrast, and insufficient axial resolution, which impedance its applications in basic and translational research. In this dissertation, I presented potential solutions to overcome the limitations above.In the first part of this …
Multi-Dimensional Single-Molecule Nanoscopy: Fundamental Limits And Novel Approaches, Oumeng Zhang
Multi-Dimensional Single-Molecule Nanoscopy: Fundamental Limits And Novel Approaches, Oumeng Zhang
McKelvey School of Engineering Graduate Student Theses & Dissertations
Single molecules (SMs) have become important tools for studying nanoscale dynamics in biological studies since they were first optically observed in 1989. Numerous techniques, termed single molecule orientation localization microscopy (SMOLM), have been developed to measure the position and orientation of SMs. Due to the challenging signal-to-background ratio (SBR) in typical SM experiments, it is critical to understand whether an imaging system is optimal for a specific target sample. However, the maximum theoretical limit of measurement performance has yet to be quantified. In Chapter 3. We first develop a mathematical framework to compute the accuracy limit in measuring the rotational …
Signaling Studies Of Protein-Peptide Binding On Microelectrode Arrays, Kendra White
Signaling Studies Of Protein-Peptide Binding On Microelectrode Arrays, Kendra White
Arts & Sciences Graduate Student Theses and Dissertations
Electrochemical methods provide unique opportunities for non-traditional synthesis and analytical studies. Using electrochemistry, we are able to synthesize individually addressable molecular surfaces on microelectrode arrays and then utilize the surface to probe interactions between receptors and their biological targets. To date, cyclic voltammetry signals can be used to detect biological interactions between proteins and small molecules on the surface of an array, however those signals are often amplified by the presence of a large number of small molecules by any given electrode. This amplification makes it difficult to obtain binding data using the arrays that can be compared with existing …
Acoustic Radiation Force And Its Application For Cell Manipulation And Ion Channels Activation, Xiangjun Peng
Acoustic Radiation Force And Its Application For Cell Manipulation And Ion Channels Activation, Xiangjun Peng
McKelvey School of Engineering Graduate Student Theses & Dissertations
Sound is a stress wave that carries energy and momentum flux. Scattered sound waves can generate acoustic radiation force that can be used to manipulate particles or cells. This dissertation demonstrates the physics behind cell manipulation by ultrasound. The work begins with a detailed analysis of the mechanics of using standing surface acoustic waves to fabricate acoustic tweezers for contactless particle manipulation using acoustic radiation force. Models to design and analyze acoustic radiation force have traditionally relied on plane wave theories that cannot predict how standing surface acoustic waves can levitate cells in the direction perpendicular to the substrate. We …
Deep Learning For Automatic Microscopy Image Analysis, Shenghua He
Deep Learning For Automatic Microscopy Image Analysis, Shenghua He
McKelvey School of Engineering Graduate Student Theses & Dissertations
Microscopy imaging techniques allow for the creation of detailed images of cells (or nuclei) and have been widely employed for cell studies in biological research and disease diagnosis in clinic practices.Microscopy image analysis (MIA), with tasks of cell detection, cell classification, and cell counting, etc., can assist with the quantitative analysis of cells and provide useful information for a cellular-level understanding of biological activities and pathology. Manual MIA is tedious, time-consuming, prone to subject errors, and are not feasible for the high-throughput cell analysis process. Thus, automatic MIA methods can facilitate all kinds of biological studies and clinical tasks. Conventional …
Developing Methods For Diversifying Molecular Scaffolds Directly On A Microelectrode Array, Nai-Hua Yeh
Developing Methods For Diversifying Molecular Scaffolds Directly On A Microelectrode Array, Nai-Hua Yeh
Arts & Sciences Graduate Student Theses and Dissertations
Microelectrode arrays contain collections of spatially isolated electrodes that can be individually addressed. Thus, the arrays have the potential to support synthesis of molecular libraries if unique members of the library can be located next to unique electrodes in the array. The result would be an intriguing platform for screening the molecules in the library against biological receptors in order to identify high-affinity ligands for those targets, especially since the arrays themselves can be directly used in the signaling studies. To expand the capabilities of the arrays, the goal of this thesis is to develop the new array chemistry needed …
Differentiating Human Embryonic Stem Cells In Micropatterns To Study Cell Fate Specification And Morphogenetic Events During Gastrulation, Kyaw Thu Minn
McKelvey School of Engineering Graduate Student Theses & Dissertations
During mammalian embryogenesis, the first major lineage segregation occurs when embryonic epiblast, and extraembryonic trophectoderm and hypoblast arise in the blastocyst. In the next fundamental and conserved phase of animal embryogenesis known as gastrulation, extraembryonic cells provide signals to epiblast to instruct embryonic patterning, and epiblast gives rise to germ layers ectoderm, mesoderm, and endoderm, that will establish all embryonic tissues. Proper specification and morphogenesis of germ layers during gastrulation is vital for correct embryonic development. Due to ethical and legal restrictions limiting human embryo studies, human gastrulation is poorly understood. Our knowledge of human gastrulation has largely been derived …
The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu
The Roles Of Plasmepsins Ix And X In Malaria Parasite Biology, Armiyaw Sebastian Nasamu
Arts & Sciences Graduate Student Theses and Dissertations
Proteases of the malaria parasite Plasmodium falciparum have been targeted for drug discovery for decades. The P. falciparum genome encodes ten aspartic proteases called plasmepsins, which are involved in diverse cellular processes. In this work we address the roles of two of these plasmepsins, plasmepsins IX and X (PM IX and X), the two least studied aspartic proteases in blood stage malaria parasites till date. We explore the essentiality of these proteases in parasite development, attempt to identify their substrates and the ability to drug them. We show that PM IX is essential for erythrocyte invasion, acting on rhoptry secretory …
Modeling The Effects Of Distribution System Topology On Water Quality, Chun-Ying Chao
Modeling The Effects Of Distribution System Topology On Water Quality, Chun-Ying Chao
McKelvey School of Engineering Graduate Student Theses & Dissertations
Inadequate treatment of drinking water causes the formation of disinfection by-products and the regrowth of harmful microbial species. Various studies have addressed the problem of water quality monitoring, but very few have employed topological analysis, a valuable mathematical tool widely applied in biological, business, and social research. This thesis examines the relationship between the topological properties of water distribution systems and water-quality models. In particular, the research proposes a novel framework for mapping network topological attributes to water-quality models. This research adopts topological metrics to assess the accuracy of the predictions of chlorine concentrations in dead ends. It examines four …
On The Fabrication And Development Of Tissue On A Chip Devices With Included Perfused Vasculatures, Usama Ismail
On The Fabrication And Development Of Tissue On A Chip Devices With Included Perfused Vasculatures, Usama Ismail
McKelvey School of Engineering Graduate Student Theses & Dissertations
The advent of Tissue-on-a-Chip (TiOC) devices has provided a novel way for researchers to approach biological study and drug development. As a platform that enables human in vivo conditions to be accurately replicated ex vivo, TiOC can accelerate both fundamental biological research to answer basic questions regarding tissue behavior and function (e.g., cell-cell interactions in the tumor microenvironment (TME)) and translational research that includes testing of standard and novel therapeutics. The reported work focuses on development of processes and technologies common to two classes of TiOC. The first device is a single-layer, multi-compartment microfluidic device for investigation of pancreatic …
Microfluidic Assessment Of Stem Cell-Derived Pancreatic Beta Cells, Arvind Rajamani Srivatsava
Microfluidic Assessment Of Stem Cell-Derived Pancreatic Beta Cells, Arvind Rajamani Srivatsava
McKelvey School of Engineering Graduate Student Theses & Dissertations
Contemporary and traditional methods of perifusional analysis of cells, pancreatic β cells in particular, involve the utilization of costly equipment exhibiting difficulties in setup and inflexibilities in operation and application. Microfluidic devices in general are inexpensive, easy to fabricate and are capable of screening multiple microenvironmental conditions, with the potential to generate concentration gradients for the study of biological phenomena such as cell migration. Utilization of these devices for cellular fluorescence imaging is also possible, paving the way for more sophisticated methods of dynamic assessment. Herein, we fabricated a pre-designed microfluidic device from photolithography, containing microwells capable of immobilizing human …
The Evolutionary And Functional Roles Of Synonymous Codon Usage In Eukaryotes, Zhen Peng
The Evolutionary And Functional Roles Of Synonymous Codon Usage In Eukaryotes, Zhen Peng
Arts & Sciences Graduate Student Theses and Dissertations
Most amino acids are encoded by multiple synonymous codons. Although alternative usage of synonymous codons does not affect the amino acid sequences of proteins, researchers have been reporting evidence for functional synonymous codon usage at the species- and gene-specific levels for over four decades. It has been shown that variations in synonymous codon usage can affect phenotypes through diverse mechanisms such as shaping translation efficiency and mRNA stability. On the other hand, the common view that cellular and organismal phenotypes are primarily determined by proteins whose functions are primarily determined by amino acid sequences, often drives the assumption that synonymous …
Genetic And Biological Studies On Solanum Plants: Insights Into The Leaf Wax Alkane Paleoclimate Proxy, Amanda Lorraine Dorothy Bender
Genetic And Biological Studies On Solanum Plants: Insights Into The Leaf Wax Alkane Paleoclimate Proxy, Amanda Lorraine Dorothy Bender
Arts & Sciences Graduate Student Theses and Dissertations
The hydrogen isotopic composition (δ2H) of precipitation records fluxes of water in the hydrological cycle, and can reflect climatic variables such as temperature and humidity. Leaf wax n-alkanes can record δ2H of precipitation; consequently, n-alkanes extracted from sedimentary archives are commonly used as proxies for paleoenvironmental reconstruction. However, the utility of the leaf wax paleoclimate proxy is modulated by uncertainty about how physiological processes affect hydrogen isotopic compositions during alkane biosynthesis. This work aims to improve our understanding of the leaf wax paleoclimate proxy by examining biological and environmental sources of variability on cuticular leaf waxes. We used Solanum (tomato) …
Specificity Determination By Paralogous Winged Helix-Turn-Helix Transcription Factors, Adam Joyce
Specificity Determination By Paralogous Winged Helix-Turn-Helix Transcription Factors, Adam Joyce
Arts & Sciences Graduate Student Theses and Dissertations
Transcription factors (TFs) localize to regulatory regions throughout the genome, where they exert physical or enzymatic control over the transcriptional machinery and regulate expression of target genes. Despite the substantial diversity of TFs found across all kingdoms of life, most belong to a relatively small number of structural families characterized by homologous DNA-binding domains (DBDs). In homologous DBDs, highly-conserved DNA-contacting residues define a characteristic ‘recognition potential’, or the limited sequence space containing high-affinity binding sites. Specificity-determining residues (SDRs) alter DNA binding preferences to further delineate this sequence space between homologous TFs, enabling functional divergence through the recognition of distinct genomic …
Teleterrestrial: The Universe Of Technological And Natural Scenes, Nat Rainer
Teleterrestrial: The Universe Of Technological And Natural Scenes, Nat Rainer
Graduate School of Art Theses
In the Universe of Technical and Natural scenes, is Telerrarin. Telerrain is composed from my point of view as an artist. This terrain of combined forms is seen in three scenes that assemble technology, humanity, and the natural world. Each scene is set in different landscapes: the desert, the countryside, and the ocean. As an artist, I see these settings with the vision of a director that drives the atmosphere, life forms, and cyclical verves that make these landscapes real. As a writer, my voice describes how technology, humanity, and the natural world fit together, and then asserts the kinds …
Biophysical Studies Of The Intracellular Domains Of The Egfr Family Of Receptor Tyrosine Kinases, Kwabena A N Sarpong
Biophysical Studies Of The Intracellular Domains Of The Egfr Family Of Receptor Tyrosine Kinases, Kwabena A N Sarpong
Arts & Sciences Graduate Student Theses and Dissertations
The epidermal growth factor receptor and its three orthologues, HER2, HER3 and HER4 have been the subject of intensive basic, clinical and translational research due to their involvement in cancers. These proteins are part of elaborate networks that interact with a myriad of other molecules to effect diverse signaling pathways and affect cellular processes such as migration, apoptosis, cell differentiation and so on. In addition to the formation of preformed dimers, it is well established that ligand engagement leads to receptor dimerization in all family members, except HER2. In the past decade, it has been shown that their intracellular domains …
Discovery And Functional Implication Of Genetic Alterations Associated With Clonal Hematopoietic Expansion, Mingchao Xie
Discovery And Functional Implication Of Genetic Alterations Associated With Clonal Hematopoietic Expansion, Mingchao Xie
Arts & Sciences Graduate Student Theses and Dissertations
Cancers, including hematologic malignancies, arise as a result of the stepwise accumulation of mutations. Some early mutations that potentially initiate clonal expansion might exist in patients many years before they develop obvious disease symptoms. Therefore, identifying and characterizing these early mutations are critical to understanding the genetic basis of tumorigenesis. Here, we analyzed blood-derived DNA sequencing data from 2,728 individuals without apparent hematologic malignancies and identified 77 blood-specific mutations in 31 cancer-associated genes. Importantly, 83% of all mutations occurred in 19 genes that have been previously linked to hematological malignancies, such as DNMT3A, TET2, JAK2, and ASXL1. By investigating these …
Synthesis Of Simplified Ym-254890 Analogs, Derek Thomas Rensing
Synthesis Of Simplified Ym-254890 Analogs, Derek Thomas Rensing
Arts & Sciences Graduate Student Theses and Dissertations
G Protein Coupled Receptors (GPCR’s) are responsible for a multitude of physiological, cellular, and disease processes. GPCR’s signal through non-receptor based heterotrimeric G proteins and since G proteins effectively mediate GPCR signal transduction they are attractive therapeutic targets. However, little is known about the signaling pathways associated with individual G proteins. For this reason, there is intense interest in the development of chemical probes that can help identify the downstream biochemistry of individual G proteins.One small molecule natural product that shows promise along these lines is YM-254890 (YM). YM has been shown to specifically and potently inhibit the α subunit …
The Role Of Epidermal Enhancer 923 In The Chromatin Architecture And Transcriptional Regulation Of The Epidermal Differentiation Complex, Inez Oh
Arts & Sciences Graduate Student Theses and Dissertations
The epidermis covers the surface of the skin and provides a functional barrier across the entire body. Epidermal cells or keratinocytes proliferate in the innermost basal layer and migrate upwards into the suprabasal spinous and granular layers as they differentiate, and finally into the terminally differentiated outermost stratum corneum. Keratinocytes undergoing terminal differentiation are marked by tissue-specific concomitant expression of genes encoded in the Epidermal Differentiation Complex (EDC) locus. The EDC genes are organized into four gene families - S100, Sprr, Lce, and Flg-like, which are coordinately expressed upon activation of the terminal differentiation program in keratinocytes. The molecular mechanisms …
Motor And Cargo Dynamics During Intraflagellar Transport: A Single Molecule Investigation, Anthony Paul Kovacs
Motor And Cargo Dynamics During Intraflagellar Transport: A Single Molecule Investigation, Anthony Paul Kovacs
Arts & Sciences Graduate Student Theses and Dissertations
The advent of single-molecule fluorescence imaging and super-resolution microscopy has produced a range of powerful tools that are able to interrogate biological systems at spatial and temporal resolutions that were previously thought to be well beyond the reach of the visible spectrum of light. While these new imaging techniques have already yielded impressive results across a broad range of studies, they still face a number of limitations. The work described herein aims to address some of these limitations by furthering the use of these techniques for the investigation of in vivo protein dynamics. Specifically, total internal reflection fluorescence (TIRF) microscopy …
Manipulating Electron Transfer Reactions From Micro- To Preparative Scale, Matthew Duane Graaf
Manipulating Electron Transfer Reactions From Micro- To Preparative Scale, Matthew Duane Graaf
Arts & Sciences Graduate Student Theses and Dissertations
The utilization of electron transfer reactions has allowed the transformation of a variety of substrates from polymer surfaces to highly functionalized organic molecules. The intricacies of these electron transfer reactions have been utilized to develop a new platform for building and studying addressable molecular libraries as they interact with biological targets. As a low cost, reusable alternative to other methods of these studying binding interactions, microelectrode arrays are beginning to gain traction with the scientific community as we continually push the limits of their potential. Additionally, the electron transfer techniques used to build the molecular libraries can be expanded to …