Open Access. Powered by Scholars. Published by Universities.®
- Discipline
-
- Ecology and Evolutionary Biology (51)
- Plant Sciences (38)
- Plant Biology (31)
- Biochemistry, Biophysics, and Structural Biology (24)
- Arts and Humanities (21)
-
- Biochemistry (18)
- Microbiology (18)
- Population Biology (18)
- Religion (17)
- Cell and Developmental Biology (16)
- Genetics and Genomics (16)
- Evolution (15)
- Behavior and Ethology (12)
- Cell Biology (12)
- Terrestrial and Aquatic Ecology (10)
- Environmental Microbiology and Microbial Ecology (8)
- Biomedical Engineering and Bioengineering (6)
- Engineering (6)
- Microbial Physiology (6)
- Ethics in Religion (5)
- Genetics (5)
- Molecular Genetics (4)
- Bacteriology (3)
- Biophysics (3)
- Genomics (3)
- Physical Sciences and Mathematics (3)
- Social and Behavioral Sciences (3)
- Anthropology (2)
- Keyword
-
- Biology (49)
- Bibliography (24)
- Genomics (23)
- Evolution (21)
- Cancer (20)
-
- Epigenetics (17)
- Cellular mechanotransduction (15)
- Microtubules (13)
- Development (12)
- Zebrafish (12)
- Diabetes (11)
- Genetics (11)
- Arabidopsis (10)
- Inflammation (10)
- Microbiome (10)
- Microbiota (10)
- DNA methylation (9)
- Hematopoiesis (9)
- Microglia (9)
- Cooperation (8)
- Ion channels (8)
- Macrophages (8)
- Mitochondria (8)
- RNA (8)
- Urinary tract infection (8)
- Antibiotic resistance (7)
- Arabidopsis thaliana (7)
- Bioinformatics (7)
- Community assembly (7)
- Immunotherapy (7)
- Publication Year
- Publication
- Publication Type
- File Type
Articles 721 - 750 of 1126
Full-Text Articles in Biology
Influenza A Virus Genomic Reassortment And Packaging, Graham Devin Williams
Influenza A Virus Genomic Reassortment And Packaging, Graham Devin Williams
Arts & Sciences Graduate Student Theses and Dissertations
Influenza A viruses (IAV) are a major human and environmental pathogen. IAV successfully infects a diverse host range and adaptation of new viral strains to humans may cause pandemic events with high morbidity and mortality. As a member of the Orthomyxoviridae family, IAV inherently possesses a segmented genome, which enables a process of segment transmission between viruses following cellular co-infection, a process termed reassortment. The high rate of IAV mutation and continued co-circulation of diverse viral strains in divergent host species leads to the persistent prospect for emergence of new IAV with pandemic potential. Therefore, it is of great importance …
Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur
Mechanism Of Gene Regulation By Coding Polya Tracks, Laura Lea Arthur
Arts & Sciences Graduate Student Theses and Dissertations
Regulation of gene expression is essential for cellular development and survival. The great variety and complexity of regulatory mechanisms underscores this fact. Messenger RNA stability and translational efficiency are often key determinants of gene expression. mRNA surveillance pathways, discovered for their role in degradation of aberrant mRNA, are now known to be instrumental in the regulation of physiologically correct mRNA stability. Thus, the study of cis elements in a transcript that can induce mRNA surveillance pathways has become an area of particular interest.Here I report on the mechanism of gene regulation by coding polyA tracks, defined as a sequence of …
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
The Regulation Of Extracellular Amyloid-Β Levels By Ionotropic Glutamatergic Transmission In An Alzheimer’S Disease Mouse Model, Jane Cecelia Hettinger
Arts & Sciences Graduate Student Theses and Dissertations
Brain extracellular concentration of the peptide amyloid-β (Aβ) is a major contributor to Alzheimer’s disease (AD) pathogenesis. High Aβ levels in the extracellular space precipitate aggregation of the peptide into soluble and insoluble toxic species. This process begins decades before cognitive impairment and triggers the cascade of pathology that eventually leads to AD. Synaptic activity is key to the regulation of extracellular Aβ levels. Presynaptic activity drives the production of Aβ, while postsynaptic receptor activation exhibits more nuanced regulation. For example, high levels of NMDA receptor (NMDA-R) activation have been shown to decrease Aβ production through the extracellular signal-regulated kinase …
Bridging The Translational Gap Between Rodent And Human Pain Research, Tayler Diane Sheahan
Bridging The Translational Gap Between Rodent And Human Pain Research, Tayler Diane Sheahan
Arts & Sciences Graduate Student Theses and Dissertations
The treatment of chronic pain is an immense clinical and societal burden rooted in the ineffectiveness and adverse side effects of existing analgesics. Extensive efforts have been directed towards the development of novel pain therapies with maximal efficacy and minimal unwanted effects; however, putative therapeutic targets identified in preclinical rodent models rarely translate in clinical trials. The poor translational record of basic pain research findings has been attributed, in part, to the use of suboptimal rodent pain models and behavioral endpoints used to assess putative analgesics, as well as differences in the pharmacological profiles of rodents and humans. The work …
Regulation Of Early Zebrafish Embryogenesis By Calcium Signaling And Dachsous1b Cadherin, Jiakun Chen
Regulation Of Early Zebrafish Embryogenesis By Calcium Signaling And Dachsous1b Cadherin, Jiakun Chen
Arts & Sciences Graduate Student Theses and Dissertations
Early animal embryogenesis entails a dynamic combination of embryonic cleavages, axial patterning, and gastrulation movements to shape a basic body plan. The underlying molecular signaling responsible for regulating this process remains poorly understood. In this thesis work, I first review recent progress in understanding of gastrulation movements in various model organisms brought by advances in imaging techniques. The externally developing and optically translucent zebrafish embryo is an ideal model organism to study vertebrate embryonic development by in vivo imaging. The objective of my thesis research is to leverage experimental advantages in the zebrafish model to uncover novel regulators and elucidate …
Analysis Of Argonaute-Small Rna-Transcription Factor Circuits Controlling Leaf Development, John Steen Hoyer
Analysis Of Argonaute-Small Rna-Transcription Factor Circuits Controlling Leaf Development, John Steen Hoyer
Arts & Sciences Graduate Student Theses and Dissertations
Experimental studies of plant development have yielded many insights into gene regulation, revealing interactions between core transcriptional and post-transcriptional regulatory pathways present in all land plants. This work describes a direct connection between the three main small RNA-transcription factor circuits controlling leaf shape dynamics in the reference plant Arabidopsis thaliana. We used a high-throughput yeast 1-hybrid platform to identify factors directly binding the promoter of the highly specialized ARGONAUTE7 silencing factor. Two groups of developmentally significant microRNA-targeted transcription factors were the clearest hits from these screens, but transgenic complementation analysis indicated that their binding sites make only a small contribution …
Phyllotactic Regularity Requires The Paf1 Complex In Arabidopsis, Kateryna Fal, Mengying Liu, Assem Duisembekova, Yassin Refahi, Elizabeth S. Haswell, Olivier Hamant
Phyllotactic Regularity Requires The Paf1 Complex In Arabidopsis, Kateryna Fal, Mengying Liu, Assem Duisembekova, Yassin Refahi, Elizabeth S. Haswell, Olivier Hamant
Biology Faculty Research
In plants, aerial organs are initiated at stereotyped intervals, both spatially (every 137° in a pattern called phyllotaxis) and temporally (at prescribed time intervals called plastochrons). To investigate the molecular basis of such regularity, mutants with altered architecture have been isolated. However, most of them only exhibit plastochron defects and/or produce a new, albeit equally reproducible, phyllotactic pattern. This leaves open the question of a molecular control of phyllotaxis regularity. Here, we show that phyllotaxis regularity depends on the function of VIP proteins, components of the RNA polymerase II-associated factor 1 complex (Paf1c). Divergence angles between successive organs along the …
Anaerobic Oxidation Of Ethane, Propane, And Butane By Marine Microbes: A Mini Review, Rajesh Singh, Michael S. Guzman, Arpita Bose
Anaerobic Oxidation Of Ethane, Propane, And Butane By Marine Microbes: A Mini Review, Rajesh Singh, Michael S. Guzman, Arpita Bose
Biology Faculty Research
The deep ocean and its sediments are a continuous source of non-methane short-chain alkanes (SCAs) including ethane, propane, and butane. Their high global warming potential, and contribution to local carbon and sulfur budgets has drawn significant scientific attention. Importantly, microbes can use gaseous alkanes and oxidize them to CO2, thus acting as effective biofilters. A relative decrease of these gases with a concomitant 13C enrichment of propane and n-butane in interstitial waters vs. the source suggests microbial anaerobic oxidation. The reported uncoupling of sulfate-reduction (SR) from anaerobic methane oxidation supports their microbial consumption. To date, strain …
Photosensing And Thermosensing By Phytochrome B Require Both Proximal And Distal Allosteric Features Within The Dimeric Photoreceptor, E Sethe Burgie, Adam N. Bussell, Shu-Hui Lye, Tong Wang, Weiming Hu, Katrice E. Mcloughlin, Erin L. Weber, Huilin Li, Richard D. Vierstra
Photosensing And Thermosensing By Phytochrome B Require Both Proximal And Distal Allosteric Features Within The Dimeric Photoreceptor, E Sethe Burgie, Adam N. Bussell, Shu-Hui Lye, Tong Wang, Weiming Hu, Katrice E. Mcloughlin, Erin L. Weber, Huilin Li, Richard D. Vierstra
Biology Faculty Research
Phytochromes (Phys) encompass a diverse collection of bilin-containing photoreceptors that help plants and microorganisms perceive light through photointerconversion between red light (Pr) and far-red light (Pfr)-absorbing states. In addition, Pfr reverts thermally back to Pr via a highly enthalpic process that enables temperature sensation in plants and possibly other organisms. Through domain analysis of the Arabidopsis PhyB isoform assembled recombinantly, coupled with measurements of solution size, photoconversion, and thermal reversion, we identified both proximal and distal features that influence all three metrics. Included are the downstream C-terminal histidine kinase-related domain known to promote dimerization and a conserved patch just upstream …
Big Brains Stabilize Populations And Facilitate Colonization Of Variable Habitats In Birds, Trevor S. Fristoe, Andrew N. Iwaniuk, Carlos A. Botero
Big Brains Stabilize Populations And Facilitate Colonization Of Variable Habitats In Birds, Trevor S. Fristoe, Andrew N. Iwaniuk, Carlos A. Botero
Biology Faculty Research
The cognitive buffer hypothesis posits that environmental variability can be a major driver of the evolution of cognition because an enhanced ability to produce flexible behavioural responses facilitates coping with the unexpected. Although comparative evidence supports different aspects of this hypothesis, a direct connection between cognition and the ability to survive a variable and unpredictable environment has yet to be demonstrated. Here, we use complementary demographic and evolutionary analyses to show that among birds, the mechanistic premise of this hypothesis is well supported but the implied direction of causality is not. Specifically, we show that although population dynamics are more …
Plant Mechanosensitive Ion Channels: An Ocean Of Possibilities, Debarati Basu, Elizabeth S. Haswell
Plant Mechanosensitive Ion Channels: An Ocean Of Possibilities, Debarati Basu, Elizabeth S. Haswell
Biology Faculty Research
Mechanosensitive ion channels, transmembrane proteins that directly couple mechanical stimuli to ion flux, serve to sense and respond to changes in membrane tension in all branches of life. In plants, mechanosensitive channels have been implicated in the perception of important mechanical stimuli such as osmotic pressure, touch, gravity, and pathogenic invasion. Indeed, three established families of plant mechanosensitive ion channels play roles in cell and organelle osmoregulation and root mechanosensing - and it is likely that many other channels and functions await discovery. Inspired by recent discoveries in bacterial and animal systems, we are beginning to establish the conserved and …
Understanding The Relationship Between Hosts And Their Microbiome, Boahemaa Adu-Oppong
Understanding The Relationship Between Hosts And Their Microbiome, Boahemaa Adu-Oppong
Arts & Sciences Graduate Student Theses and Dissertations
Microbes are bountiful and associated with every animal and plant kingdom. Furthermore, microbes can alter host phenotype, development, health and functioning. However, this is not a one-way interaction, hosts can structure microbial communities by changing the environment to be suitable for certain microbial species. Several studies have characterized microbial communities associated with hosts to answer two2 main questions in ecology: who’s there, and what are they doing? However, two questions from the field of community ecology are often ignored (1) what forces are structuring the microbial communities (how was the community formed) and (2) how stable are these communities. Vellend …
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Mechanisms And Regulation Of Resection In Dna Damage Response, Sharad C. Paudyal
Arts & Sciences Graduate Student Theses and Dissertations
Deoxyribonucleic acid (DNA) encodes genetic information essential for cell survival and function. However, it is constantly under assault from endogenous and exogenous damaging agents that not only threaten our own survival but also affect the faithful transmission of genetic information to our offspring. Double-strand breaks (DSBs) are one of the most hazardous forms of DNA damage, which if unrepaired or improperly repaired could lead to plethora of systemic human diseases including cancer. To deal with this problem, cells have evolved with a mechanism called DNA damage response (DDR) to detect, signal, and repair the breaks by inducing multiple cellular events. …
Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald
Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald
Arts & Sciences Graduate Student Theses and Dissertations
DNA methylation is known to silence gene expression in the context of imprinting, X-chromosome inactivation, and retrotransposon silencing. However, the role of DNA methylation in silencing gene expression outside of these contexts is not fully understood. This is especially true in diseases such as cancer, where normal DNA methylation patterns are significantly altered. In breast cancer as well as nearly all cancer types, most of the genome loses DNA methylation while small regions of the genome gain methylation. DNA methylation generally correlates with decreased gene expression when present at a gene promoter. Therefore, these regions of hypo- and hyper-methylation may …
Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris
Characterization And Function Of Islet Antigen Presenting Cells During Nod Diabetes, Stephen Thomas Ferris
Arts & Sciences Graduate Student Theses and Dissertations
Here we characterized the initial antigen presenting cells (APCs) within the islet of Langerhans to ascertain their identity and functional role as it pertains to autoimmune diabetes. The activation of the adaptive immune system is induced by the innate immune system, and more specifically APCs. Therefore, it is crucial to identify the APCs that are initiating T1D in order to elucidate the break in tolerance and intervene in order to inhibit progression. We have found that there is a resident macrophage that is present in all strains of mice. This islet macrophage has a distinct transcriptional profile that is unique …
Antiviral Nucleoside Inhibitors Of Leishmania Rna Virus 1: Discovery And Mechanism, John Isaac Robinson
Antiviral Nucleoside Inhibitors Of Leishmania Rna Virus 1: Discovery And Mechanism, John Isaac Robinson
Arts & Sciences Graduate Student Theses and Dissertations
Some Leishmania parasites in the Viannia sub-genus are persistently infected with Leishmania RNA virus 1 (LRV1), a single-segmented double-stranded RNA virus belonging to the family Totiviridae. Infected parasites cause greater pathology and reach higher populations in mouse models of Leishmania infection. In human disease, LRV1+ parasites are correlated with increased frequency of treatment failure and relapse. Efficient methods to detect LRV1 and eliminate it from parasites are required to better understand the role of LRV1 in Leishmania infection. We optimized multiple techniques to measure LRV1 levels in parasites, most notably using flow cytometry to measure the amount of viral capsid …
Exploring Host-Virus Interactions In Caenorhabditis Nematodes, Kevin Chen
Exploring Host-Virus Interactions In Caenorhabditis Nematodes, Kevin Chen
Arts & Sciences Graduate Student Theses and Dissertations
Caenorhabditis elegans is a powerful model organism that has elucidated many biological questions in the fields of genetics, development, and neurobiology. In addition, C. elegans has been used in the past decade to investigate host-pathogen interactions with bacteria and fungi. The recent identification of nematode viruses that naturally infect C. elegans and Caenorhabditis briggsae provides a unique opportunity to define host-virus interactions in these model hosts.This dissertation first explored the transcriptional response of C. elegans and C. briggsae to virus infection by RNA-seq. I identified a total of 320 differentially expressed genes (DEGs) in C. elegans following Orsay virus infection. …
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 …
Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy
Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy
Arts & Sciences Graduate Student Theses and Dissertations
The seemingly limitless capacities of mammals to sense, respond, and manipulate their environments stems from their structurally and functionally diverse nervous systems. Establishing these complex behaviors requires the integration of many biological phenomena including, morphogenetic gradients, cell-cell signaling, transcriptional networks, cell migration and epigenetic gene regulation. As mammalian development progresses, these pathways coordinate the production of highly specialized neuronal and glial cells, that connect and communicate with another in an even more complex manner. While evolution has shaped a multitude of pathways to produce numerous favorable traits, it has also created an intricate system vulnerable to disease. The loss of …
Identification And Characterization Of An Interferon Stimulated Gene That Restricts Alphavirus Infection And Pathogenesis, Subhajit Poddar
Identification And Characterization Of An Interferon Stimulated Gene That Restricts Alphavirus Infection And Pathogenesis, Subhajit Poddar
Arts & Sciences Graduate Student Theses and Dissertations
Viral infection of host cells induces the Type I interferon (IFN) response, which ischaracterized by the production of hundreds of IFN-stimulated genes (ISGs). Altogether, theseISGs function to induce an antiviral state, hindering or blocking various steps of the virallifecycle. Many individual ISGs have potent and broad antiviral functions. However eliminationof a single ISG does not completely abrogate protection, suggesting that other ISGs, althoughmoderate or moderate when considered alone, must work cooperatively to provide optimalantiviral activity.In order to identify and characterize novel ISGs, an attenuated strain of the alphaviruschikungunya (CHIKV-181/25) was tested against an shRNA library of 243 curated murine genesupregulated …
Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li
Nuclear Export Factor 3 Regulates The Localization Of Small Nucleolar Rnas, Melissa Wanling Li
Arts & Sciences Graduate Student Theses and Dissertations
Metabolic diseases, such as obesity and diabetes, are associated with excess levels of lipids, which can lead to organelle dysfunction, cell death and eventually organ dysfunction. This process, termed lipotoxicity, is still not completely understood. In a genetic screen used to identify genes critical for lipotoxicity, the Schaffer lab has identified small nucleolar RNAs (snoRNAs) within the ribosomal protein L13a (Rpl13a) locus that mediate the cellular response to lipotoxic and general metabolic stress. These snoRNAs are non-canonical in that they accumulate in the cytosol after metabolic stresses like lipotoxicity and oxidative stress, suggesting that cells have specific mechanisms for regulating …
The Effect Of Dietary Fat On Obesity, Gene Expression, And Dna Methylation In Two Generations Of Mice, Madeline Rose Keleher
The Effect Of Dietary Fat On Obesity, Gene Expression, And Dna Methylation In Two Generations Of Mice, Madeline Rose Keleher
Arts & Sciences Graduate Student Theses and Dissertations
As obesity rates continue rising nationally and globally, it is crucial to understand how a high-fat diet disrupts the regulation of the genome and leads to adverse health effects. Uncovering the underlying gene expression and DNA methylation changes induced by an individual’s high-fat diet and a maternal high-fat diet can pinpoint new targets for epigenetic therapies and reveal the physiological and behavioral changes in obesity. The goal of this dissertation is to gain deeper insight into the DNA methylation and gene expression changes that occur in response to a high-fat diet.I studied the response to dietary fat within two generations …
Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli
Dna Replication Challenges: Telomeres And R Loops, Shankar Parajuli
Arts & Sciences Graduate Student Theses and Dissertations
Faithful DNA replication and repair are essential for maintaining genome stability and preventing various diseases including cancer. Both processes are executed by numerous redundant mechanisms to ensure that these processes are uninterrupted even when a primary mechanism fails. Despite this, they are not immune to challenges and failures leading to DNA damage and genome instability. These problems are more evident at the difficult-to-replicate regions of the genome such as the telomeres that cap and protect linear chromosome ends. Additionally, topological structures such as RNA:DNA hybrids, commonly referred to as R loops, can also present severe challenges to the DNA replication …
Investigation Of The Contribution Of Type 1 Pili In Enterotoxigenic Escherichia Coli (Etec) Pathogen-Host Interactions, Alaullah Sheikh
Investigation Of The Contribution Of Type 1 Pili In Enterotoxigenic Escherichia Coli (Etec) Pathogen-Host Interactions, Alaullah Sheikh
Arts & Sciences Graduate Student Theses and Dissertations
Enterotoxigenic Escherichia coli (ETEC) are one of the leading causes of death due to diarrhea in children living in developing countries. ETEC are also the leading cause of diarrhea in travelers to developing countries lacking sanitation and safe drinking water. Unfortunately, there is no broadly protective vaccine available against these important pathogens. In order to cause infection, ETEC colonize the intestinal epithelium and secrete toxins, including heat-labile toxin (LT) and/or heat-stable toxin (ST). Efficient delivery of these toxins to the cognate receptors on target intestinal cells requires direct ETEC-host interactions. Earlier studies demonstrated that ETEC facilitate interactions with host by …
Type 1 And F17-Like Pili Promote The Establishment Of The Uropathogenic E. Coli Intestinal Reservoir, Caitlin Nicole Spaulding
Type 1 And F17-Like Pili Promote The Establishment Of The Uropathogenic E. Coli Intestinal Reservoir, Caitlin Nicole Spaulding
Arts & Sciences Graduate Student Theses and Dissertations
Urinary tract infections (UTI) affect over 150 million individuals worldwide every year. These infections are associated with significant morbidity and have a sizeable economic impact, with $5 billion being spent on UTI treatment in the USA annually. Uropathogenic E. coli (UPEC) are responsible for 80% of community acquired UTIs and 65% of nosocomial UTI. The current standard of care for UTI is antibiotic therapy. However, 30-50% of women experience recurrent UTI (rUTI) despite receiving antibiotic therapy. The prevalence of single and multi-drug resistant UPEC strains has led to increased reliance on carbepenems, which are primarily reserved for multi-drug resistant infections, …
Expansion Of Microbial Virology By Impetus Of The Reduction Of Viral Dark Matter, Siddharth Ravindran Krishnamurthy
Expansion Of Microbial Virology By Impetus Of The Reduction Of Viral Dark Matter, Siddharth Ravindran Krishnamurthy
Arts & Sciences Graduate Student Theses and Dissertations
Modern metagenomic methods have rapidly accelerated the rate of viral discovery. Currently, to discover a novel virus, deep sequencing reads must align to a known reference virus. While alignment is effective at identifying closely related viruses, highly divergent viruses can often share no discernable sequence alignment with known viruses. Therefore, the accurate classification of viral dark matter – metagenomic sequences that originate from viruses but do not align to any reference virus sequences – is one of the major obstacles in not only discovering novel viruses, but also by extension, comprehensively defining the virome. As viral dark matter results fundamentally …
Robust Algorithms For Detecting Hidden Structure In Biological Data, Roman Sloutsky
Robust Algorithms For Detecting Hidden Structure In Biological Data, Roman Sloutsky
Arts & Sciences Graduate Student Theses and Dissertations
Biological data, such as molecular abundance measurements and proteinsequences, harbor complex hidden structure that reflects its underlyingbiological mechanisms. For example, high-throughput abundance measurementsprovide a snapshot the global state of a living cell, while homologousprotein sequences encode the residue-level logic of the proteins' functionand provide a snapshot of the evolutionary trajectory of the protein family.In this work I describe algorithmic approaches and analysis software Ideveloped for uncovering hidden structure in both kinds of data.Clustering is an unsurpervised machine learning technique commonly usedto map the structure of data collected in high-throughput experiments,such as quantification of gene expression by DNA microarrays orshort-read sequencing. …
The Role Of Vip Scn Neurons In Circadian Physiology And Behavior, Cristina Mazuski
The Role Of Vip Scn Neurons In Circadian Physiology And Behavior, Cristina Mazuski
Arts & Sciences Graduate Student Theses and Dissertations
Located in the ventral hypothalamus, the suprachiasmatic nucleus (SCN) is necessary for entraining daily rhythms in physiology and behavior to environmental cues. Though the 20,000 neurons of the SCN uniformly express GABA, they differ greatly in neuropeptide content. One anatomically and functionally distinct class of neuropeptidergic SCN neurons is vasoactive intestinal polypeptide (VIP). Expressed by approximately 10% of SCN neurons, VIP is necessary for synchronizing single-cell SCN rhythms to produce coherent output and sufficient for entrainment. However, little is known about the firing activity of these neurons releases VIP and results in circadian entrainment. We utilized multielectrode array technology and …
Determining The Molecular Mechanisms Of Huntington’S Disease Through Multi-Scale Modeling, Kiersten Ruff
Determining The Molecular Mechanisms Of Huntington’S Disease Through Multi-Scale Modeling, Kiersten Ruff
Arts & Sciences Graduate Student Theses and Dissertations
Huntington’s disease (HD) is associated with a mutational CAG repeat expansion within exon 1 of the huntingtin (Htt) gene. Post-transcriptional processing leads to the generation of N-terminal Htt protein fragments (Htt-NTFs), including those that encompass exon 1 (Httex1). Within Httex1, the CAG-repeat encoded polyglutamine (polyQ) tract is flanked N-terminally by a 17-residue amphipathic stretch (N17) and C-terminally by a 50-residue proline rich (PR) domain. Htt-NTFs, including Httex1, are among the smallest fragments that recapitulate HD pathology in mouse models. However, the direct link between Htt-NTFs with polyQ expansions and neurodegeneration that leads to HD remains unresolved. Despite being a monogenic …
Sequence Determinants Of The Individual And Collective Behaviour Of Intrinsically Disordered Proteins, Alexander S. Holehouse
Sequence Determinants Of The Individual And Collective Behaviour Of Intrinsically Disordered Proteins, Alexander S. Holehouse
Arts & Sciences Graduate Student Theses and Dissertations
Intrinsically disordered proteins and protein regions (IDPs) represent around thirty percent of the eukaryotic proteome. IDPs do not fold into a set three dimensional structure, but instead exist in an ensemble of inter-converting states. Despite being disordered, IDPs are decidedly not random; well-defined - albeit transient - local and long-range interactions give rise to an ensemble with distinct statistical biases over many length-scales. Among a variety of cellular roles, IDPs drive and modulate the formation of phase separated intracellular condensates, non-stoichiometric assemblies of protein and nucleic acid that serve many functions. In this work, we have explored how the amino …