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Full-Text Articles in Life Sciences

Non-Coding Rna Features Critical To The Replication Of Hiv-1, Matthew A. Takata Jan 2019

Non-Coding Rna Features Critical To The Replication Of Hiv-1, Matthew A. Takata

Student Theses and Dissertations

The HIV-1 genome contains RNA sequences and structures that control many aspects of viral replication including, but not limited to transcription, splicing, nuclear export, translation, packaging and reverse transcription. Despite this extensive existing catalogue of RNA sequences that are critical to its replication, chemical probing and targeting mutagenesis studies suggest that the HIV-1 genome may contain many more RNA elements of unknown important function. To determine whether there are additional, undiscovered cis-acting RNA elements in the HIV-1 genome that are important for viral replication, we conducted a global synonymous mutagenesis experiment. Sixteen mutant proviruses containing clusters of ~50 to ~200 ...


Center Manifold Dynamics In Randomly Coupled Oscillators And In Cochlea, Dimitrios Moirogiannis Jan 2019

Center Manifold Dynamics In Randomly Coupled Oscillators And In Cochlea, Dimitrios Moirogiannis

Student Theses and Dissertations

In dynamical systems theory, a fixed point of the activity is called nonhyperbolic if the linearization of the system around the fixed point has at least one eigenvalue with zero real part. The center manifold existence theorem guarantees the local existence of an invariant subspace of the activity, known as a center manifold, around nonhyperbolic fixed points. A growing number of theoretical and experimental studies suggest that neural systems utilize dynamics on center manifolds to display complex, nonlinear behavior and to flexibly adapt to wide-ranging sensory input parameters. In this thesis, I will present two lines of research exploring nonhyperbolicity ...


Neural Mechanisms That Control An Innate Foraging Behavior In Caenorhabditis Elegans, Alejandro Lopez-Cruz Jan 2019

Neural Mechanisms That Control An Innate Foraging Behavior In Caenorhabditis Elegans, Alejandro Lopez-Cruz

Student Theses and Dissertations

The ability to efficiently locate food is critical for survival. Thus, animals modify their foraging patterns based on recent experience and current conditions to increase their likelihood of finding food. One highly conserved foraging strategy is local search, an intensive exploration over several minutes of the region where food resources were last encountered. As time since the last food encounter passes, animals transition to global search strategies to explore distant areas. The local-to-global search foraging pattern has been observed in fish, reptiles, insects, birds, and mammals, yet few studies ask how an animal’s brain generates this ancient behavior. Here ...


A Stress-Induced Trna Depletion Response Mediates Codon-Based Translational Repression And Growth Suppression, Doowon Huh Jan 2019

A Stress-Induced Trna Depletion Response Mediates Codon-Based Translational Repression And Growth Suppression, Doowon Huh

Student Theses and Dissertations

Eukaryotic transfer RNAs (tRNAs) can become fragmented upon various cellular stresses, generating tRNA-derived RNA fragments (tRFs). Though this process has been observed for numerous cellular stresses and in many species ranging from plant cells to yeast and human cells, it is still poorly characterized and understood. Such tRNA fragmentation has previously been thought to affect a small fraction of the tRNA pool and was thus presumed to not affect the role of tRNAs in translation. We report that in human cells, oxidative stress can rapidly generate tRFs derived from tyrosyl tRNAGUA—resulting in a significant depletion of the precursor tRNA ...


The Role And Control Of Wnt Signalling In An Hesc Model Of Human Primitive Streak, Iain Martyn Jan 2019

The Role And Control Of Wnt Signalling In An Hesc Model Of Human Primitive Streak, Iain Martyn

Student Theses and Dissertations

In amniotes, gastrulation is marked by the creation of the primitive streak (PS) and is largely controlled by WNT, BMP, and ACTIVIN/NODAL signalling. Despite detailed characterization in model organisms, the human PS and the role these pathways play in its formation and patterning remains a mystery. In this work I focused on understanding the role and control of the WNT pathway in human PS development. Due to the ethical limitations of working with human embryos, I used an in vitro human embryonic stem cell (hESC) micropatterned “gastruloid” system. I first showed that in the human PS there is a ...


Sensory Coding And Olfactory Integration In Caenorhabditis Elegans, May Dobosiewicz Jan 2019

Sensory Coding And Olfactory Integration In Caenorhabditis Elegans, May Dobosiewicz

Student Theses and Dissertations

Animals must sense their external environments to guide meaningful behavior. The nematode Caenorhabditis elegans, for example, uses volatile cues to navigate toward food from a distance. How does an animal integrate the olfactory information from its environment? Here, I ask how multiple sensory neurons drive and shape one interneuron’s activity. C. elegans senses several odors, including the bacterial metabolite diacetyl, using the AWA sensory neurons. AWA forms chemical and electrical synapses onto several interconnected interneurons, which contribute to chemotaxis toward attractive odors like diacetyl. One AWA target is the interneuron AIA, which is connected to AWA via a putative ...


Multimodal Strategies Of Host-Seeking Mosquitoes, Molly Zhen Liu Jan 2019

Multimodal Strategies Of Host-Seeking Mosquitoes, Molly Zhen Liu

Student Theses and Dissertations

Mosquitoes use multiple sensory modalities, including olfaction, thermosensation, and vision, to hunt human hosts and obtain a blood-meal for egg production. Any individual sensory cue is an incomplete signal of a human host, and so a mosquito must integrate multimodal sensory information before committing to approaching and biting a person. Mosquito host-seeking behavior is thus a particularly fruitful model for studying multimodal integration because of its robustness, intricacy, and public health importance. Using tethered and free flight assays, we have teased apart responses to attractive visual and thermal cues in female Aedes aegypti, the yellow fever mosquito, uncovering their contributions ...


Elucidation Of The Functional Architecture Of The Early Pre-Ribosomal Processing Machinery In Yeast, Mirjam Hunziker Jan 2019

Elucidation Of The Functional Architecture Of The Early Pre-Ribosomal Processing Machinery In Yeast, Mirjam Hunziker

Student Theses and Dissertations

Ribosomes carry out one of the most fundamental functions of life - the translation of genetic information into functional proteins. The pivotal role of the ribosome in the cell is reflected in its immensely complicated and energy-consuming assembly pathway. The maturation of a eukaryotic ribosome involves more than 200 non-ribosomal factors and the activity of all three RNA polymerases. In yeast, ribosome biogenesis starts with the transcription of the 35S pre-ribosomal RNA in the nucleolus. This large RNA molecule contains three of the four ribosomal RNAs separated by several internal and external transcribed spacer regions. The 5’ external transcribed spacer (5 ...


Gpcr Activation Of The G Protein-Gated Inward-Rectifier Potassium Channel, Kouki Touhara Jan 2019

Gpcr Activation Of The G Protein-Gated Inward-Rectifier Potassium Channel, Kouki Touhara

Student Theses and Dissertations

Heart rate is tightly regulated by the combined effects of the sympathetic and parasympathetic branches of the autonomic nervous system. These two branches control heart rate by stimulating different G protein-coupled receptors (GPCRs), which in turn activate ion channels that modify the electrical properties of cardiac pacemaker cells. Sympathetic stimulation accelerates heart rate through activation of beta-adrenergic receptors (βARs), which open excitatory ion channels through the stimulatory G protein (Gαs) pathway. Parasympathetic stimulation slows heart rate through activation of the muscarinic acetylcholine receptor M2 (M2Rs), which inhibits the effect of sympathetic stimulation through the inhibitory G protein (Gαi) pathway. M2Rs ...


Oxytocin, Dopamine, And The Neuromodulation Of Mating Behavior In C. Elegans, Meghan Aileen Lockard Jan 2019

Oxytocin, Dopamine, And The Neuromodulation Of Mating Behavior In C. Elegans, Meghan Aileen Lockard

Student Theses and Dissertations

No abstract provided.


The Role Of Zmynd8 In Immunoglobulin Class Switch Recombination, Daniel Benjamin Rosen Jan 2019

The Role Of Zmynd8 In Immunoglobulin Class Switch Recombination, Daniel Benjamin Rosen

Student Theses and Dissertations

Class switch Recombination (CSR) also known as Immunoglobulin (Ig) Class switching is a genomic recombination/deletion reaction that diversifies the effector component of the antibody response but preserves antigen specificity. CSR is initiated by the enzyme activation induced cytidine deaminase (AID), which produces nucleotide mismatches in actively transcribed immunoglobulin heavy chain (Igh) switch donor and acceptor DNA. The 3’ Regulatory Region (3’RR), a prototypical super-enhancer located at the 3’ of the Igh locus, is essential for acceptor switch region transcription, but the mechanism by which it regulates this process is not well defined. After targeting by AID, nearby mismatches ...


Dopamine And The Temporal Dependence Of Learning And Memory, Annie Handler Jan 2019

Dopamine And The Temporal Dependence Of Learning And Memory, Annie Handler

Student Theses and Dissertations

Animal behavior is largely influenced by the seeking out of rewards and avoidance of punishments. Positive or negative reinforcements, like a food reward or painful shock, impart meaningful valence onto sensory cues in the animal’s environment. The ability of animals to form associations between a sensory cue and a rewarding or punishing reinforcement permits them to adapt their future behavior to maximize reward and minimize punishments. Animals rely on the timing of events to infer the causal relationships between cues and outcomes –– sensory cues that precede a painful shock in time become associated with its onset and are imparted ...


Characterizing Human Transfer Rnas By Hydro-Trnaseq And Par-Clip, Tasos Gogakos Jan 2018

Characterizing Human Transfer Rnas By Hydro-Trnaseq And Par-Clip, Tasos Gogakos

Student Theses and Dissertations

The participation of tRNAs in fundamental aspects of biology and disease necessitates an accurate, experimentally confirmed annotation of tRNA genes, and curation of precursor and mature tRNA sequences. This has been challenging, mainly because RNA secondary structure and nucleotide modifications, together with tRNA gene multiplicity, complicate sequencing and read mapping efforts. To address these issues, I developed hydro-tRNAseq, a method based on partial alkaline RNA hydrolysis that generates fragments amenable for sequencing. To identify transcribed tRNA genes, I further complemented this approach with Photoactivatable Crosslinking and Immunoprecipitation (PAR-CLIP) of SSB/La, a conserved protein involved in pre-tRNA processing. My results ...


Cell Cycle Control By Cyclin-Cdks In Chlamydomonas Reinhardtii, Kenneth C. Atkins Jan 2018

Cell Cycle Control By Cyclin-Cdks In Chlamydomonas Reinhardtii, Kenneth C. Atkins

Student Theses and Dissertations

The cell cycle consists of a series of events, including replication and segregation of the genome, that occurs in order to ensure successful reproduction of cells. In fungi and animals, this process is carefully regulated by a set of protein complexes with alternating, oscillating activity. A well established model has been developed for animals and fungi in which the activities of various cyclin-dependent kinases (CDKs) and the anaphase promoting complex (APC) drive the events of the cell cycle at the appropriate time and in the appropriate order. While this model has been extremely useful for understanding cell division in these ...


Cell Type Specific Roles Of Serotonin Receptor 4 In The Hippocampus And Neocortex In Emotion And Cognition, Remzi Karayol Jan 2018

Cell Type Specific Roles Of Serotonin Receptor 4 In The Hippocampus And Neocortex In Emotion And Cognition, Remzi Karayol

Student Theses and Dissertations

Anxiety and mood disorders are the most prevalent classes of mental disorders. However, current treatments for these debilitating diseases are limited due to their delayed onset of action and numerous side effects, emphasizing the need for faster acting and more efficacious therapies. Preclinical studies indicate a critical role for Serotonin Receptor 4 (5-HT4R, product of the Htr4 gene) in this direction as drugs that activate this receptor show fast-acting antidepressant-like properties. Unfortunately, 5-HT4R is widely expressed in the periphery, limiting its use as a direct therapeutic target due to various side effects. Understanding the cell type ...


Daple Orients And Patterns Sensory Hair Bundles In The Inner Ear, Kimberly Siletti Jan 2018

Daple Orients And Patterns Sensory Hair Bundles In The Inner Ear, Kimberly Siletti

Student Theses and Dissertations

The planar orientation of mammalian cells necessitates the integration of diverse pathways. In the inner ear, at least two systems regulate the planar polarity of the hair bundle. The core planar cell polarity (PCP) proteins coordinate the orientations of hair cells across the epithelial plane. The cell-intrinsic patterning of each hair bundle is implemented independently by a G-protein complex comprising the alpha subunit of heterotrimeric G-protein (Gαi) and Leu-Gly-Asn repeat-enriched protein (LGN). Classically known for orienting the mitotic spindle, these proteins form an apical blueprint for hair-bundle development. Although the primary cilium also participates in each of these pathways, the ...


Multi-Modal Effects Of The Repellent Deet Across Protostomia, Emily Jane Dennis Jan 2018

Multi-Modal Effects Of The Repellent Deet Across Protostomia, Emily Jane Dennis

Student Theses and Dissertations

DEET (N, N-diethyl-m-toluamide) is the most broadly effective and widely used personal repellent available, yet we do not understand what makes it so effective. Even in well-studied species like Drosophila melanogaster flies and Aedes aegypti mosquitoes, many mysteries remain as to how DEET can affect behavior in these species. For example, Ae. aegypti mosquitoes are attracted to human arms. When an arm is covered in DEET, wild-type mosquitoes are not attracted to the arm, while mutant mosquitoes that lack the odorant receptor co-receptor (orco), approach the arm, but rarely bite. We investigated this orco-independent DEET repellency in Ae. aegypti and ...


Surface Coat Replacement Dynamics And Antigen Glycosylation In T. Brucei Influence Evasion Of The Host Antibody Response, Jason M. Pinger Jan 2018

Surface Coat Replacement Dynamics And Antigen Glycosylation In T. Brucei Influence Evasion Of The Host Antibody Response, Jason M. Pinger

Student Theses and Dissertations

The protozoan parasite Trypanosoma brucei, a causative agent of human and animal trypanosomiasis, evades host immunity through antigenic variation of its variant surface glycoprotein (VSG) coat. During infection, the VSG coat elicits a robust antibody response, but the parasite escapes antibody-mediated clearance by repeatedly accessing its large genomic VSG repertoire and switching expression to antigenically distinct VSGs. Much of our knowledge of the process of VSG switching and the extent of VSG diversity has come from genetic analyses, but deep understanding of the T. brucei host-pathogen interface also requires examination of these topics at the protein level. In this thesis ...


Igdb-2, An Ig/Fniii Protein, Binds The Ion Channel Lgc-34 And Controls Sensory Compartment Morphogenesis In C. Elegans, Wendy Wang Jan 2018

Igdb-2, An Ig/Fniii Protein, Binds The Ion Channel Lgc-34 And Controls Sensory Compartment Morphogenesis In C. Elegans, Wendy Wang

Student Theses and Dissertations

Sensory organ glia surround neuronal receptive endings (NREs), forming a specialized extracellular space, or compartment, important for neuronal activity, and reminiscent of glia-ensheathed synapses in the central nervous system. Sensory organ glia are conserved across organisms, but our current understanding of how they form sensory compartments is generally lacking. To date, the Caenorhabditis elegans amphid sensory organ has provided critical insight into some of these developmental processes. DAF-6, a Patched-related protein, was previously shown to be required in amphid glia to restrict sensory compartment size. LIT-1, a Nemo-like kinase, and SNX-1, a retromer component, antagonize DAF-6 and promote compartment expansion ...


Making Ribosomes: Biochemical And Structural Studies Of Early Ribosome Biogenesis In Yeast, Malik Chaker-Margot Jan 2018

Making Ribosomes: Biochemical And Structural Studies Of Early Ribosome Biogenesis In Yeast, Malik Chaker-Margot

Student Theses and Dissertations

The ribosome is a complex macromolecule responsible for the synthesis of all proteins in the cell. In yeast, it is made of four ribosomal RNAs and 79 proteins, asymmetrically divided in a small and large subunit. In a growing yeast cell, more than 2000 ribosomes are assembled every minute. The ribosome is assembled through a highly complex process involving more than 200 trans-acting factors. Ribosome assembly begins in the nucleolus where RNA polymerase I transcribes a long polycistronic RNA, the 35S preribosomal RNA which contains the sequences for three of the four ribosomal RNAs, as well as spacer sequences which ...


Investigating Genetic (In)Compatibility Between Temperate Phages And Crispr-Cas Systems In Staphylococcus Aureus, Gregory W. Goldberg Jan 2018

Investigating Genetic (In)Compatibility Between Temperate Phages And Crispr-Cas Systems In Staphylococcus Aureus, Gregory W. Goldberg

Student Theses and Dissertations

Prokaryotic organisms employ various mechanisms for defending against parasitism by viruses and other mobile genetic elements. One form of defense comprises the adaptive immune systems derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci and CRISPR-associated (cas) genes. CRISPR-Cas immune systems enable the acquisition of heritable resistance to specific mobile genetic elements on the basis of nucleic acid sequence recognition, but do not necessarily discriminate between target elements which are burdensome and those which are beneficial. My thesis is concerned with the consequences of CRISPR-Cas immunity directed at a particular breed of bacterial DNA viruses, known as temperate phages ...


Targeting The Cd4 Binding Site Of Hiv, Lotta Von Boehmer Jan 2018

Targeting The Cd4 Binding Site Of Hiv, Lotta Von Boehmer

Student Theses and Dissertations

The immunologic obstacles to develop a broadly neutralizing antibody (bNAb) against HIV by vaccine mandate for methodical testing in order to understand and direct the immune response. A mouse model with the predicted human heavy chain variable domain of a bNAb precursor or mature version introduced into the mouse heavy chain immunoglobulin locus proved to be very useful. The immunoglobulin heavy-chain of the predicted germline (GLVH) or mature mutated (MuVH) version of 3BNC60 was knocked into the JH4 locus in mice. 3BNC60 is a bNAb that targets the CD4 binding site (CD4bs) of HIV-11,2 and belongs to the ...


The Characterization Of A Novel Complex Implicated In The Initiation Of Apoptosis, Thomas Hsiao Jan 2018

The Characterization Of A Novel Complex Implicated In The Initiation Of Apoptosis, Thomas Hsiao

Student Theses and Dissertations

Apoptosis, which is one of many different types of programmed cell death, is widely utilized as a mechanism to eliminate unwanted cells. The ability of cells to undergo apoptosis is required not only for development in many organisms, but also to maintain proper homeostasis; too little apoptosis can result in cancer whereas too much can lead to degenerative diseases. Apoptosis has been well studied at events that take place at or downstream of the mitochondria; these steps are rigorous and predictable, making them easy to study. However, little is known about early, decision-making events that occur upstream of the mitochondria ...


Modeling Alzheimer's Disease In Induced Pluripotent Stem Cells, Andrew Gregg Jan 2018

Modeling Alzheimer's Disease In Induced Pluripotent Stem Cells, Andrew Gregg

Student Theses and Dissertations

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and is now the 5th leading cause of death in the United States. The pathologic hallmarks of AD include the deposition of extracellular plaques of aggregated amyloid-β (Aβ) and intracellular neurofibrillary tangles of tau aggregates (NFTs). Autosomal dominant inheritance of AD has been attributed to genetic mutations in three key genes: amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN-2). Together, these pathologic findings and genetics provided the framework for the amyloid cascade hypothesis, which states that Aβ deposition is a necessary, early event that is upstream of ...


Robustness Enhancement Of Sensory Transduction By Hair Bundles, Andrew Robert Milewski Jan 2018

Robustness Enhancement Of Sensory Transduction By Hair Bundles, Andrew Robert Milewski

Student Theses and Dissertations

How do biological systems ensure robustness of function despite developmental and environmental variation? Our sense of hearing boasts exquisite sensitivity, precise frequency discrimination, and a broad dynamic range. Experiments and modeling imply, however, that the auditory system achieves this performance for only a narrow range of parameter values. Although the operation of some systems appears to require precise control over parameter values, I describe how the function of the ear might instead be made robust to parameter perturbation. The sensory hair cells of the cochlea are physiologically vulnerable: small changes in parameter values could compromise hair cells' ability to detect ...


Netrin Guides Spinal Commissural Axons To The Midline At Long Range Through The Receptors Dcc And Neogenin, Sze Sing Shaun Teo Jan 2018

Netrin Guides Spinal Commissural Axons To The Midline At Long Range Through The Receptors Dcc And Neogenin, Sze Sing Shaun Teo

Student Theses and Dissertations

During neurodevelopment, commissural axons are guided to the ventral midline in a remarkably precise and stereotyped way. Netrin, a secreted laminin-related protein, provides the major attractive cue for midline guidance. It is thought to act at long-range, functioning either in solution (chemotaxis) or bound to surfaces (haptotaxis). A gradient of Netrin-1 along the dorsal-ventral axis of the spinal cord is thought to attract commissural axons to the midline, with the floor plate being a major source of diffusible Netrin. However, this view has recently been challenged. To address this controversy and determine what role, if any, floor plate-derived Netrin-1 plays ...


Characterization And Reconstitution Of S-Palmitoylated Ifitm3 Antiviral Activity, Avital Percher Jan 2018

Characterization And Reconstitution Of S-Palmitoylated Ifitm3 Antiviral Activity, Avital Percher

Student Theses and Dissertations

To rapidly detect early stage infections the innate immune system maintains an assortment of pathogen recognition mechanisms interspersed throughout both the extracellular and intracellular environments. These sensors recognize key components of viral, bacterial and fungal pathogens, and stimulate an inflammatory response which leads to the expression of an extensive network of host defense proteins. One such canonical network is regulated by type I interferon. This pathway responds to viral infections by upregulating hundreds of interferon stimulated genes (ISG) critical for host immunity. One of the more pivotal proteins for viral control is interferon-induced transmembrane protein 3 (IFITM3). IFITM3 is a ...


The Role Of Neuronal Pentraxin 1 In Promoting Pancreatic Cancer Progression, Yuehyi Gloria Wu Jan 2018

The Role Of Neuronal Pentraxin 1 In Promoting Pancreatic Cancer Progression, Yuehyi Gloria Wu

Student Theses and Dissertations

Pancreatic cancer is a deadly malignancy because it is usually diagnosed at an advanced stage and does not respond to the majority of treatments. More than 80% of patients present with advanced stage disease at the time of diagnosis and metastatic pancreatic cancer has a median survival of eight to eleven months under current standard of care. In the United States, pancreatic cancer is the fourth leading cause of cancer death. Efforts in using targeted agents to treat pancreatic cancer have mostly been fruitless. The dismal survival outcome of this disease and lack of success in clinical trials indicate the ...


A Role For Pi31-Mediated Proteasome Regulation In Proteostasis And Neuronal Health, Sandra Jones Jan 2018

A Role For Pi31-Mediated Proteasome Regulation In Proteostasis And Neuronal Health, Sandra Jones

Student Theses and Dissertations

The specific and timely degradation of proteins is achieved by the Ubiquitin-Proteasome System (UPS), which governs a variety of cellular processes such as apoptosis, cell cycle progression, protein quality control, and metabolism. Using this system, cells maintain homeostasis by quickly and irreversibly altering signaling pathways in response to changing environmental stimuli. Protein degradation by UPS requires two consecutive steps, 1) the covalent attachment of the substrate by ubiquitin and 2) the delivery of the substrate to the 26S proteasome for breakdown and recycling of reusable ubiquitin. The 26S proteasome is a 2.5- MDa multicatalytic protease consisting of two subcomplexes ...


Single Cell Analysis Of The Hiv-1 Latent Reservoir, Lillian Brumer Cohn Jan 2018

Single Cell Analysis Of The Hiv-1 Latent Reservoir, Lillian Brumer Cohn

Student Theses and Dissertations

Human immunodeficiency virus type 1 (HIV-1), the virus that causes acquired immune deficiency syndrome (AIDS), is one of the world’s most serious health and development challenges. Worldwide there are approximately 36.7 million people living with HIV, and tens of millions have died of AIDS-related causes since the beginning of the epidemic. Treatment of HIV-1 infection with combinations of antiretroviral drugs has significantly reduced the death rate and improved the quality of life of HIV-1 infected individuals. Despite over thirty years of HIV-1 research, however, both a cure and a vaccine remain elusive. Complete eradication of HIV-1 by antiretroviral ...