Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 14 of 14

Full-Text Articles in Life Sciences

Hox Gene Regulation And Function During Zebrafish Embryogenesis: A Dissertation, Steven E. Weicksel Oct 2013

Hox Gene Regulation And Function During Zebrafish Embryogenesis: A Dissertation, Steven E. Weicksel

GSBS Dissertations and Theses

Hox genes encode a conserved family of homeodomain containing transcription factors essential for metazoan development. The establishment of overlapping Hox expression domains specifies tissue identities along the anterior-posterior axis during early embryogenesis and is regulated by chromatin architecture and retinoic acid (RA). Here we present the role nucleosome positioning plays in hox activation during embryogenesis. Using four stages of early embryo development, we map nucleosome positions at 37 zebrafish hox promoters. We find nucleosome arrangement to be progressive, taking place over several stages independent of RA. This progressive change in nucleosome arrangement on invariant sequence suggests that trans-factors play an ...


A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang Sep 2013

A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang

GSBS Dissertations and Theses

Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether ...


Hiv-1 And The Nucleolus: A Role For Nucleophosmin/Npm1 In Viral Replication: A Dissertation, Tracy E. Schmidt Aug 2013

Hiv-1 And The Nucleolus: A Role For Nucleophosmin/Npm1 In Viral Replication: A Dissertation, Tracy E. Schmidt

GSBS Dissertations and Theses

The nucleolus is a plurifunctional organelle with dynamic protein exchange involved in diverse aspects of cell biology. Additionally, the nucleolus has been shown to have a role in the replication of numerous viruses, which includes HIV-1. Several groups have reported HIV-1 vRNA localization within the nucleolus. Moreover, it has been demonstrated the HIV-1 Rev protein localizes to the nucleolus and interacts with nucleolar proteins, including NPM1. Despite evidence for a nucleolar involvement during replication, a functional link has not been demonstrated. I investigated whether introncontaining vRNAs have a Rev-mediated nucleolar localization step prior to export. Furthermore, I examined whether NPM1 ...


Morphogenetic Requirements For Embryo Patterning And The Generation Of Stem Cell-Derived Mice: A Dissertation, Yeonsoo Yoon Jul 2013

Morphogenetic Requirements For Embryo Patterning And The Generation Of Stem Cell-Derived Mice: A Dissertation, Yeonsoo Yoon

GSBS Dissertations and Theses

Cell proliferation and differentiation are tightly regulated processes required for the proper development of multi-cellular organisms. To understand the effects of cell proliferation on embryo patterning in mice, we inactivated Aurora A, a gene essential for completion of the cell cycle. We discovered that inhibiting cell proliferation leads to different outcomes depending on the tissue affected. If the epiblast, the embryonic component, is compromised, it leads to gastrulation failure. However, when Aurora A is inactivated in extra-embryonic tissues, mutant embryos fail to properly establish the anteroposterior axis. Ablation of Aurora A in the epiblast eventually leads to abnormal embryos composed ...


A Role For Intraflagellar Transport Proteins In Mitosis: A Dissertation, Alison R. Bright Jun 2013

A Role For Intraflagellar Transport Proteins In Mitosis: A Dissertation, Alison R. Bright

GSBS Dissertations and Theses

Disruption of cilia proteins results in a range of disorders called ciliopathies. However, the mechanism by which cilia dysfunction contributes to disease is not well understood. Intraflagellar transport (IFT) proteins are required for ciliogenesis. They carry ciliary cargo along the microtubule axoneme while riding microtubule motors. Interestingly, IFT proteins localize to spindle poles in non-ciliated, mitotic cells, suggesting a mitotic function for IFT proteins. Based on their role in cilia, we hypothesized that IFT proteins regulate microtubule-based transport during mitotic spindle assembly. Biochemical investigation revealed that in mitotic cells IFT88, IFT57, IFT52, and IFT20 interact with dynein1, a microtubule motor ...


Investigating Cancer Molecular Genetics Using Genome-Wide Rna Interference Screens: A Dissertation, Ryan W. Serra Jun 2013

Investigating Cancer Molecular Genetics Using Genome-Wide Rna Interference Screens: A Dissertation, Ryan W. Serra

GSBS Dissertations and Theses

The development of RNAi based technologies has given researchers the tools to interrogate processes as diverse as cancer biology, metabolism and organ development. Here I employ genome-wide shRNA screens to discover the genes involved in two different processes in carcinogenesis, oncogene-induced senescence [OIS] and epigenetic silencing of tumor suppressor genes [TSGs].

OIS is a poorly studied yet significant tumor suppressing mechanism in normal cells where they enter cell cycle arrest [senescence] or programmed cell death [apoptosis] in the presence of an activated oncogene. Here I employ a genomewide shRNA screen and identify a secreted protein, IGFBP7, that induces senescence and ...


Investigation Of Multiple Concerted Mechanisms Underlying Stimulus-Induced G1 Arrest In Yeast: A Dissertation, Patricia A. Pope Jun 2013

Investigation Of Multiple Concerted Mechanisms Underlying Stimulus-Induced G1 Arrest In Yeast: A Dissertation, Patricia A. Pope

GSBS Dissertations and Theses

Progression through the cell cycle is tightly controlled, and the decision whether or not to enter a new cell cycle can be influenced by both internal and external cues. For budding yeast one such external cue is pheromone treatment, which can induce G1 arrest. Two distinct mechanisms are known to be involved in this arrest, one dependent on the arrest protein Far1 and one independent of Far1, but the exact mechanisms have remained enigmatic. The studies presented here further elucidate both of these mechanisms.

We looked at two distinct aspects of the Far1-independent arrest mechanism. First, we studied the role ...


The Role And Regulation Of Etv2 In Zebrafish Vascular Development: A Dissertation, John C. Moore May 2013

The Role And Regulation Of Etv2 In Zebrafish Vascular Development: A Dissertation, John C. Moore

GSBS Dissertations and Theses

Etv2 is an endothelial-specific ETS transcription factor that is essential for endothelial differentiation and vascular morphogenesis in vertebrates. However, etv2 expression dynamics during development and the mechanisms regulating it are poorly understood. I found that etv2 transcript and protein expression are highly transient during zebrafish vascular development, with both expressed early during development and then subsequently downregulated. Inducible knockdown of Etv2 in zebrafish embryos prior to mid-somitogenesis, but not later, causes severe vascular defects, suggesting a role for Etv2 in specifying angioblasts from the lateral mesoderm. I further demonstrate that the 3’UTR of etv2 is post-transcriptionally regulated in part ...


The Notch1-C-Myc Pathway Mediates Leukemia-Initiating Cell Activity In Mouse T-All Models: A Dissertation, Jessica M. Tesell May 2013

The Notch1-C-Myc Pathway Mediates Leukemia-Initiating Cell Activity In Mouse T-All Models: A Dissertation, Jessica M. Tesell

GSBS Dissertations and Theses

Although cure rates have significantly improved for children with T-cell acute lymphoblastic leukemia (T-ALL), 20-30% undergo induction failure or relapse with most succumbing to disease. Leukemia-initiating cells (L-ICs) are hypothesized to be resistant to conventional chemotherapy and radiation and are thereby responsible for disease recurrence. Using an in vivo limiting dilution assay, we previously showed that the murine T-ALL L-IC is quite rare, with only 0.003-0.05% of cells capable of initiating disease, and demonstrated that the L-IC is a subset of the leukemic DN3 thymic progenitor population. Work described in this thesis validates the L-IC assay using two ...


Role Of Map4k4 In Skeletal Muscle Differentiation: A Dissertation, Mengxi Wang May 2013

Role Of Map4k4 In Skeletal Muscle Differentiation: A Dissertation, Mengxi Wang

GSBS Dissertations and Theses

Skeletal muscle is a complicated and heterogeneous striated muscle tissue that serves critical mechanical and metabolic functions in the organism. The process of generating skeletal muscle, myogenesis, is elaborately coordinated by members of the protein kinase family, which transmit diverse signals initiated by extracellular stimuli to myogenic transcriptional hierarchy in muscle cells. Mitogen-activated protein kinases (MAPKs) including p38 MAPK, c-Jun N terminal kinase (JNK) and extracellular signal-regulated protein kinase (ERK) are components of serine/threonine protein kinase cascades that play important roles in skeletal muscle differentiation. The exploration of MAPK upstream kinases identified mitogen activated protein kinase kinase kinase kinase ...


Nuclear Organization In Breast Cancer: A Dissertation, Jason R. Dobson Apr 2013

Nuclear Organization In Breast Cancer: A Dissertation, Jason R. Dobson

GSBS Dissertations and Theses

The nuclear matrix (NM) is a fibrogranular network of ribonucleoproteins upon which transcriptional complexes and regulatory genomic sequences are organized. A hallmark of cancer is the disorganization of nuclear architecture; however, the extent to which the NM is involved in malignancy is not well studied.

The RUNX1 and RUNX2 proteins form complexes within the NM to promote hematopoiesis and osteoblastogenesis, respectively at the transcriptional level. RUNX1 and RUNX2 are both expressed in breast cancer cells (BrCCs); however, their genome-wide BrCC functions are unknown. RUNX1 and RUNX2 activate many tumor suppressor pathways in blood and bone lineages, respectively, including attenuation of ...


Role Of Autophagy In Post-Mitotic Midbody Fate And Function: A Dissertation, Tse-Chun Kuo Mar 2013

Role Of Autophagy In Post-Mitotic Midbody Fate And Function: A Dissertation, Tse-Chun Kuo

GSBS Dissertations and Theses

The midbody (MB) is a proteinaceous complex formed between the two daughter cells during cell division and is required for the final cell separation event in late cytokinesis. After cell division, the post-mitotic midbody, or midbody derivative (MBd), can be retained and accumulated in a subpopulation of cancer cells and stem cells, but not in normal diploid differentiated cells. However, the mechanisms by which MBds accumulate and function are unclear. Based on this, I hypothesize that the MBd is degraded by autophagy after cell division in normal diploid differentiated cells, whereas non-differentiated cells have low autophagic ...


Runx Expression In Normal And Osteoarthritic Cartilage: Possible Functions Of Runx Proteins In Chondrocytes: A Dissertation, Kimberly T. Leblanc Feb 2013

Runx Expression In Normal And Osteoarthritic Cartilage: Possible Functions Of Runx Proteins In Chondrocytes: A Dissertation, Kimberly T. Leblanc

GSBS Dissertations and Theses

The Runx family of transcription factors supports cell fate determination, cell cycle regulation, global protein synthesis control, and genetic as well as epigenetic regulation of target genes. Runx1, which is essential for hematopoiesis; Runx2, which is required for osteoblast differentiation; and Runx3, which is involved in neurologic and gut development; are expressed in the growth plate during chondrocyte maturation, and in the chondrocytes of permanent cartilage structures. While Runx2 is known to control genes that contribute to chondrocyte hypertrophy, the functions of Runx1 and Runx3 during chondrogenesis and in cartilage tissue have been less well studied.

The goals of this ...


Role Of The Cytoplasmic Polyadenylation Element Binding Proteins In Neuron: A Dissertation, Aparna Oruganty Feb 2013

Role Of The Cytoplasmic Polyadenylation Element Binding Proteins In Neuron: A Dissertation, Aparna Oruganty

GSBS Dissertations and Theses

Genome regulation is an extremely complex phenomenon. There are various mechanisms in place to ensure smooth performance of the organism. Post-transcriptional regulation of gene expression is one such mechanism. Many proteins bind to mRNAs and regulate their translation. In this thesis, I have focused on the Cytoplasmic Polyadenylation Element Binding family of proteins (CPEB1-4); a group of sequence specific RNA binding proteins important for cell cycle progression, senescence, neuronal function and plasticity. CPEB protein binds mRNAs containing a short Cytoplasmic Polyadenylation Element (CPE) in 3’ untranslated Region (UTR) and regulates the polyadenylation of these mRNAs and thereby controls translation. In ...