Dartmouth Digital Library Program

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Understanding the mechanisms of transcriptional control by the oncoprotein MYC / by Mandeep Kaur.
Even though 25 years have passed since the discovery of MYC, a complete understanding of the mechanism(s) of transcriptional control by this oncogenic transcription factor has not been achieved. Mcy is one of the most frequently deregulated...
Dartmouth Dissertations

The macromolecular assembly of NuMA.
Nucleoproteins. ; Macromolecules. ; Cell organelles -- Formation. ; Mitosis. ; Phosphorylation.
Dartmouth Dissertations

Regulation of cohesion, recombination and chromosome core dynamics during Drosophila meiosis.
Drosophila -- Cytogenetics. Meiosis. Sister chromatid exchange. Chromosome Segregation.
Accurate chromosome segregation during mitosis and meiosis requires that sister-chromatid cohesion hold sisters together until the appropriate time. In addition, meiotic cohesion is necessary for normal synaptonemal complex (SC) and homologous...
Dartmouth Dissertations

Characterization of two Saccharamyces cerevisiae genes involved in mRNA export.
Messenger RNA -- Physiological transport. ; Saccharomyces cerevisiae -- Genetics. ; Proteins -- Synthesis -- Genetic aspects.
I report the further characterization of an essential S. cerevisiae nucleoporin, RAT7/NUP159, shown previously to be involved in mRNA export. The Rat7p/Nup159p can be divided into three domains: an N-terminal domain, a central repeat domain, and a...
Dartmouth Dissertations

A reciprocal relationship between Scavenger Receptor-A and toll-like receptor 4 in bacterial phagocytosis and endotoxic shock resistance.
Cell receptors. Phagocytosis -- Immunological aspects. Septic shock -- Immunological aspects. Bacterial diseases -- Immunological aspects. Natural immunity. Medical Term Receptors, Cell Surface -- physiology. Toll-Like Receptors -- physiology.
An organism's long-term survival is critically dependent on its ability to protect itself from pathogenic microbial infections. The first line of defense against such infections is the branch of the immune response referred to as the innate immune...
Dartmouth Dissertations

Molecular analysis of novel ER membrane proteins important for homeostasis in Saccharomyces cerevisiae.
Membrane proteins -- Physiological transport. Biological transport -- Regulation. Proteins -- Biodegradation. Proteins -- Synthesis -- Regulation. Endoplasmic reticulum. Cellular control mechanisms. Saccharomyces cerevisiae -- Molecular aspects.
Endoplasmic reticulum (ER) homeostasis requires the coordination of anabolic and catabolic activities. A primary function of the ER is the biosynthesis and export of secretory proteins and lipids. Anterograde transport of only properly folded and...
Dartmouth Dissertations

Structural, functional, and biochemical approaches to understanding the role of the C1 microtubule of the flagellar central apparatus.
Microtubules. Dynein. ; Eukaryotic cells -- Motility.
The eukaryotic flagellum is a complex organelle that uses the force generated by dynein motors to cause beating motion of the flagellum. The central apparatus of eukaryotic flagella has been implicated in the regulation of dynein-driven motility....
Dartmouth Dissertations

A proteomics approach to NIMA-related kinase signaling in mitosis / by Sierra N. Cullati
NIMA-related kinases (Neks) control several aspects of cell division downstream of master mitotic regulators such as Cdk1 and Plk1. Though depletion of Nek6, Nek7, or Nek9 results in cytokinesis failure, to date no molecular mechanism has been...
Dartmouth Dissertations

A novel role for visual arrestin in endocytosis-mediated retinal degeneration.
Phospholipase C -- Mechanism of action. Retinal degeneration -- Pathophysiology. Retinal degeneration -- Genetic aspects. Endocytosis. Rhodopsin. Cellular signal transduction. Light -- Physiological effect. Arrestin. Clathrin. Adaptor Proteins
Mutations in the Drosophila retinal-specific Phospholipase C (NORPA) cause massive retinal degeneration within five days of constant light exposure. We have previously shown that in norpA mutants persistent complexes between the light receptor...
Dartmouth Dissertations

Investigation of vesicle fusion in ER to Golgi transport.
Membrane proteins -- Physiological transport. ; Biological transport -- Regulation. ; Cell membranes. ; Golgi apparatus. ; Endoplasmic reticulum. ; Saccharomyces cerevisiae -- Cytology.
Many intracellular transport events are mediated by vesicles that bud from donor membranes and then fuse with acceptor membranes. The transport of secretory proteins between the ER and Golgi compartments of the yeast Saccharomyces cerevisiae has...
Dartmouth Dissertations

Investigation of Sec22p in ER to Golgi transport in Saccharomyces cerevisiae.
Membrane proteins -- Physiological transport. Membrane fusion. Biological transport -- Regulation. Cell membranes. Saccharomyces cerevisiae -- Cytology. Golgi apparatus. Endoplasmic reticulum.
Vesicle mediated intracellular transport through the secretory pathway requires the formation of transport vesicles from a donor compartment followed by vesicle tethering and fusion with an appropriate acceptor compartment. The anterograde...
Dartmouth Dissertations

Solution structure determination of core binding factor ß(1-141) and map of CPFα binding site.
Transcription factors -- Structure. ; Genetic transcription. ; DNA-binding proteins.
Core binding factor (CBF) is a heterodimeric transcription factor that is essential for a number of developmental process including hemotopoiesis and bone development. CBFs contain a DNA-binding CBFα. subunit and a non-DNA binding CBFß. subunit...
Dartmouth Dissertations

Characterization of pathways and intermediates involved in CD40 signal transduction.
CD antigens. ; Cellular signal transduction. ; Immune response -- Regulation. ; Antigens CD40.
Dartmouth Dissertations

Novel roles for phosphorylation and coiled-coil domains in septin organization.
The septins are a class of GTP-binding cytoskeletal proteins conserved throughout eukaryotes. They were first described as a set of cell division cycle mutants in the budding yeast Saccharomyces cerevisiae, but since their initial discovery septins...
Dartmouth Dissertations

3D structure determination of reduced human glutaredoxin: Biophysical and biochemical characterization of CBFß proteins.
Transcription factors. ; Glutaredoxin -- Structure. ; DNA-protein interactions.
Dartmouth Dissertations

Light and temperature entrainment of a circadian clock or two.
Circadian rhythms. ; Light -- Physiological effect. ; Temperature -- Physiological effect. ; Photoreceptors. ; Arabidopsis thaliana -- Effect of light on. ; Arabidopsis thaliana -- Effect of temperature on. ; Arabidopsis thaliana -- Genetics. ;...
The synchronization of a circadian clock to the outside environment is a crucial step in the daily life of most organisms. Light and temperature signals help an organism reset its circadian clock. In the model plant Arabidopsis thaliana, a number...
Dartmouth Dissertations

The Polycomb Group Complex PRC1 collaborates with cohesin to stabilize the synaptonemal complex and promote crossovers during meiosis / by Pei Zhou.
Lightning -- New Mexico -- Observations.;""Photon emission."";""X-rays -- Spectra -- Measurement -- Instruments."";""X-rays -- Spectra -- Mathematical models.""
Dartmouth Dissertations

Exploring new players in the Neurospora core clock and its output
The unifying theme of this work has been the use of forward genetics to identify three new genes - each thought to play an important yet unrecognized role in either the core circadian oscillator of Neurospora crassa , or in its main physiological...
Dartmouth Dissertations

Understanding PDZ affinity and selectivity: all residues considered / by Jeanine F. Amacher.
PDZ protein-protein interaction domains recognize short linear motif (SLiM) sequences typically at the extreme C-terminus of a target protein. These domains often act as scaffolds, connecting target proteins to additional interaction and catalytic...
Dartmouth Dissertations

Fusion proteins and select lipids cooperate as membrane receptors for the soluble snare Vam7p / by Vidya Karunakaran.
Yeast vacuole fusion involves three transmembrane SNAREs and a unique soluble SNARE, Vam7p. This SNARE cycles between vacuolar membrane-bound and cytosolic state. In its membrane-bound state, it is able to participate in vacuolar fusion by...
Dartmouth Dissertations

Constitutively activated PI3K signaling accelerates tumor initiation and progression in breast and lung cancers / by Mee Rie Sheen.
Phosphatidylinositol 3-kinase (PI3K) is a major positive regulator of the PI3K signaling pathway that regulates many important cellular functions including growth, proliferation, survival, metabolism, and angiogenesis. The PIK3CA gene, encoding the...
Dartmouth Dissertations

SGA screen identifies a cytoplasmic role for Dbp5/Rat8 and a novel player in nuclear pore complex biogenesis.
Nuclear membranes. Membrane proteins. Genetic regulation.
The coordination and coupling of the several steps in mRNA biogenesis helps to ensure proper regulation of gene expression. The DEAD-box helicase Dbp5/Rat8 is an essential mRNA export factor that has also been implicated in other steps of mRNA...
Dartmouth Dissertations

Targeting CFTR endocytic interactions as a therapeutic strategy in cystic fibrosis / by Lemira Sahar Al Ayyoubi.
Despite the recent FDA approval of the potentiator drug Kalydeco for treatment of cystic fibrosis (CF), only a small (3-5%) portion of patients benefit from this drug. Other functional classes of drugs including correctors are under clinical...
Dartmouth Dissertations

Modulation of swarming motility in Pseudomonas aeruginosa / by Dae Gon Ha.
Swarming motility is a flagella-dependent surface motility, and is also a form of bacterial group behavior. Similar to its counterpart biofilm formation, our understanding of swarming motility has been hampered by its complex set of requirements...
Dartmouth Dissertations

Disruption of the Cbfa2 or Cbfb gene causes necrosis and hemorrhages in the central nervous system and blocks definitive hematopoiesis.
Transcription factors. Genetic transcription. Hematopoiesis -- Genetic aspects. Central nervous system -- Growth -- Genetic aspects. Mice -- Nervous system -- Genetic aspects. Mammals -- Embryology -- Genetic aspects.
Dartmouth Dissertations

Characterization of two S. Cerevisiae genes implicated in mRNA export: RAT7, encoding a novel nuclear pore complex protein and NPL3, encoding a putative hnRNP protein.
Messenger RNA -- Genetic aspects. Proteins -- Synthesis -- Genetic aspects. Saccharomyces cerevisiae -- Genetics.
Dartmouth Dissertations

From target discovery to high-throughput screens--selective CAL PDZ inhibitors as candidate CF therapeutics
Peptides -- Therapeutic use. ; Chloride channels -- Pathophysiology. ; Ligands (Biochemistry) ; Protein-protein interactions. ; Cystic fibrosis -- Molecular aspects. ; High throughput screening (Drug development) ; PDZ Domains. ; Cystic Fibrosis...
PDZ domains are protein:protein interaction domains that serve as molecular scaffolds, especially in the case of specialized cellular environments like polarized airway epithelial cells of the human lung. Historically the domains have been thought...
Dartmouth Dissertations

Isolation and functional characterization of yeast vacuole snare complexes.
Membrane proteins -- Physiological transport. ; Plant proteins -- Physiological transport. ; Biological transport -- Regulation. ; Plant vacuoles. Saccharomyces cerevisiae -- Physiology.
Eukaryotic cells are compartmentalized into membrane-enclosed organelles. Genetic screens and reconstituted biochemical assays have revealed that intracellular protein trafficking is mediated by a conserved mechanism of vesicle budding, transport,...
Dartmouth Dissertations

The importance of dosage of core binding factors α and ß in hematopoietic development.
Hematopoiesis -- Regulation. ; Transcription factors.
Core Binding Factors (CBFs) are members of a small family of transcription factors that play critical roles in a number of mammalian developmental processes. CBFs are heterodimers consisting of a CBFα subunit, which contacts and binds DNA at the...
Dartmouth Dissertations

A complex of the BCL2-like protein CED-9 and the BH3-only protein EGL-1 recruits DRP-1 to mitochondria and promotes mitochondrial fission
Mitochondria -- Physiology.; Fission (Biology) ; Guanosine triphosphatase. ; Caenorhabditis elegans. ; Caenorhabditis elegans Proteins -- physiology. ; GTP Phosphohydrolases -- physiology. ; bcl2-Associated Death Protein -- physiology.
Dartmouth Dissertations

Molecular function of the MADS floral organ identity proteins of APETALA3 and PISTILLATA in Arabidopsis.
Arabidopsis -- Genetics. Arabidopsis -- Molecular aspects. Transcription factors. DNA-binding proteins. Flowers -- Morphogenesis -- Molecular aspects.
APETALA3 ( AP3 ) and PISTILLATA ( PI ) are floral organ identity genes that are necessary and sufficient for petal and stamen development. Surprisingly little is known about molecular mechanisms by which AP3 and PI proteins direct floral organ...
Dartmouth Dissertations

Circadian and non-circadian oscillators in Neurospora crassa.
Circadian rhythms. Neurospora crassa -- Genetics. Genetic transcription -- Regulation. Choline. Temperature. Circadian Rhythm -- genetics. Choline Deficiency -- genetics.
The circadian clock of the filamentous fungus, Neurospora crassa, consists of a frequency-white-collar ( frq-wc ) based and transcription-translation-derived oscillator. Negative feedback regulation is essential for the oscillatory process, in...
Dartmouth Dissertations

Kinetochore influence on mitotic spindle structure.
Spindle (Cell division). Microtubules. Mitosis. Kinetochores -- physiology. Microtubule-Associated Proteins -- physiology.
Proper chromosome alignment and segregation depends on the formation and maintenance of a bipolar mitotic spindle with focused poles. It has been shown that microtubules are focused at spindle poles through the combined actions of centrosomes and a...
Dartmouth Dissertations

Targeting anaphase catastrophe through CDK inhibition in lung cancer / by Shanhu Hu
Aneuploidy is frequently detected in human cancers and is implicated in carcinogenesis. Pharmacological targeting of aneuploidy is an attractive therapeutic strategy, as this would preferentially eliminate malignant over normal cells. Our prior...
Dartmouth Dissertations

Biological significance of VIVID photocycle length and the control of gene expression by the Neurospora clock / by Arko Dasgupta
Sensing light from the environment using photoreceptors is of great adaptive significance to eukaryotes. A prominent feature of the photochemistry of these receptors is the photocycle length, the time taken to decay from the initial signaling light...
Dartmouth Dissertations

Investigation of ER-Golgi membrane proteins influencing COPII tethering and fusion / by Indrani Mukherjee
Protein secretion is executed by the secretory pathway, which involves the delivery of membrane and soluble secretory proteins in vesicle intermediates that capture newly-synthesized proteins assembled in the endoplasmic reticulum (ER) and then...
Dartmouth Dissertations

Cellular organization in syncytia : nuclear autonomy and cytosolic organization across kingdoms / by Samantha Elizabeth Roberts
All cells must organize their cytoplasm in order to carry out functions properly and survive in different environments, and the requirement for organization is increased in large, multinucleate cells. It has long been known that membrane-bound...
Dartmouth Dissertations

Mechanisms regulating interphase condensin II control of genome organization / by Huy Nguyen
How the genome is shaped directly influences how it is expressed. In fact, the genome is organized at many different levels, each imparting specific regulation over transcription. Fundamental principles regulating genome organization are poorly...
Dartmouth Dissertations

Probing a receptor-binding domain of interleukin-2 by combinatorial cassette mutagenesis.
Interleukin-2. ; Mutagenesis.
Dartmouth Dissertations

The role of the Drosophila SK channel in sensory processing and behavior / by Ahmad Nawwaf Abou Tayoun.
Partially ordered sets. ; Forcing (Model theory). ; Set theory.
Dartmouth Dissertations

Discovering MII1 regulated pathways in hematopoietic stem cells.
Hematopoietic stem cells. ; Hematopoietic stem cell disorders -- Genetic aspects. ; Genetic transcription -- Regulation. ; Leukemia -- Genetic aspects. ; Cell proliferation. ; Myeloid-Lymphoid Leukemia Protein -- genetics.
Hematopoietic stem cells (HSCs) balance self-renewal with the continuous production of the suitable numbers of lineage-restricted progenitor cells. In this work we demonstrate that the Mixed lineage leukemia 1 (Mll1) gene is essential for this...
Dartmouth Dissertations

Biological and receptor binding properties of interleukin-2 analogs employing site-directed mutagenesis and filamentous phage display.
Interleukin-2 -- Derivatives. ; Ligand binding (Biochemistry). ; Mutagenesis.
Dartmouth Dissertations

An analysis of an ecdysterone response element from the Drosophila hsp27 gene.
Ecdysone. ; Gene expression. ; Drosophila -- Genetics. ; Heat shock proteins.
Dartmouth Dissertations

Light and circadian regulation in Neurospora crassa.
Neurospora crassa -- Effect of light on. ; Neurospora crassa -- Genetics. ; Circadian rhythms. ; Genetic transcription -- Regulation. ; Cryptochrome. ; Phytochrome.
Dartmouth Dissertations

Synthesis of porphobilinogen and studies on the synthesis of cobyric acid.
Tetrapyrroles -- Synthesis. ; Porphyrins -- Synthesis. ; Vitamin B12 -- Synthesis.
This thesis describes the synthetic study of two biologically related natural products: porphobilinogen (PBG) and cobyric acid. PBG is the key intermediate in the biosynthesis of all naturally occurring tetrapyrrolic 'pigments of life', including...
Dartmouth Dissertations

Control of developmental timing in Caenorhabditis elegans by lin-14.
Caenorhabditis elegans -- Genetics. ; Caenorhabditis elegans -- Growth. ; Cellular control mechanisms. ; Heterochrony (Biology). ; Developmental genetics.
The heterochronic gene lin-14 affects certain somatic cell-fate choices during post-embryonic development in C. elegans. In lin-14 mutants, cells express stage-specific developmental programs, such as cell divisions or dauer entry, at inappropriate...
Dartmouth Dissertations

Runx1 expression and function in the development of murine definitive hematopoietic stem cells and blood lineages.
Transcription factors. ; Hematopoietic stem cells -- Genetic aspects. ; DNA-binding proteins. ; Mutation (Biology).
Dartmouth Dissertations

Vibrio cholerae H-NS: investigation of regulated genes and structure-function analysis.
Vibrio cholerae -- Genetics. ; DNA-binding proteins. ; Genetic transcription -- Regulation. ; Bacterial proteins.
H-NS, an abundant nucleoid associated protein, has a role in silencing the expression of a variety of environmentally regulated genes during growth under nonpermissive conditions. A genetic approach was used to study H-NS regulation of genes in...
Dartmouth Dissertations