Molecular Biology Commons^™

Investigating Autophagy Dysfunction Induced By A Parkinson's Disease-Causing Mutation In Vps35, Abir Ashfakur Rahman

Boise State University Theses and Dissertations

Parkinson’s Disease (PD) is an idiopathic disorder with no known cure. With number of cases steadily rising around the world, it is imperative to turn to the underlying cellular and molecular mechanisms of the disease manifestation and neurodegeneration to craft novel modes of therapy. VPS35 is one of the few genes that have identified and definitively linked to familial PD. The particular mutation that has been associated is known to cause dysfunction of a key cellular process known as autophagy. This process is primarily responsible for clearance of unwanted, damaged or misfolded proteins, among other things. Our study reveals an …

Genetic And Epigenetic Investigations On Pulmonary Hypertension Syndrome In Meat Type- Chickens, Khaloud Alzahrani

Graduate Theses and Dissertations

This dissertation presents a collection of studies that investigate the genetic and epigenetic associations to ascites phenotype in broiler chickens. Ascites is a significant metabolic disease associated with fast-growing meat-type chickens (broilers) and is a terminal result of pulmonary hypertension syndrome PHS. It is a multi-factorial syndrome caused by interactions between genetic, physiological, environmental, and managemental factors. It was estimated that ascites accounts for losses of about US$1 billion annually worldwide and for over 25% of broilers mortality. Although traditional and molecular genetic methods in the selection and in performance improvements, has greatly reduced ascites frequency, yet it has not …

Thermal And Microbial Effects On Brown Macroalgae: Heat Acclimation And The Biodiversity Of The Microbiome, Charlotte Tc Quigley

Electronic Theses and Dissertations

This dissertation examines effects of stress on brown algal biology from a macroscopic scale by examining the whole aquaculture crops, and at a microscopic level by examining the macroalgal microbiome, across the vertical stress gradient of the intertidal zone and across the latitudes of their biogeographic ranges. Thermal stress negatively affected seedstock gametophytes of the kelp Alaria esculenta isolated from northern and southern locations in Maine. However, previous thermal stress had a positive effect on growth of the next-generation sporophytes. Alaria esculenta has potential as a kelp crop in Maine’s sea vegetable aquaculture sector and implementing this protocol may allow …

Myc Distant Enhancers Underlie Ovarian Cancer Susceptibility At The 8q24.21 Locus, Anxhela Gjyshi Gustafson

USF Tampa Graduate Theses and Dissertations

Ovarian cancer is a leading cause of death among women diagnosed with cancer. Mortality rate is high because an overwhelming majority of new cases are diagnosed with late-stage disease when the survival statistics are very poor with an overall 5-year survival rate of less than 40%. Despite the large burden of disease, the etiology of ovarian cancer is not well understood. In addition to linkage studies that have identified highly penetrant cancer susceptibility genes such as BRCA1 and BRCA2, the emergence of Genome Wide Association Studies (GWAS) in the last decade has facilitated the identification of common genetic variants with …

The Role Of Mesenchymal Stromal Cells And Classical Dendritic Cells In The Maintenance And Regulation Of The Bone Marrow Niche, Jingzhu Zhang

Arts & Sciences Electronic Theses and Dissertations

The bone marrow niche is an important microenvironment for the regulation of normal and malignant hematopoiesis. The first discovered niche component is mesenchymal stromal cells, which are the major source for the production and secretion of multiple niche factors. Mesenchymal stromal cells are heterogeneous and various transgenes have been used to target non-identical but overlapping subpopulations. To further characterize the heterogeneity of mesenchymal stromal cells, we tested the targeting specificity of three tissue-specific Cre-recombinase transgenes. We show that in addition to osteoblasts, Ocn-Cre targets a majority of Cxcl12-abundant reticular (CAR) cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset …

Characterization Of The Celf6 Rna Binding Protein: Effects On Mouse Vocal Behavior And Biochemical Function, Michael A. Rieger

Arts & Sciences Electronic Theses and Dissertations

Behavior in higher eukaryotes is a complex process which integrates signals in the environment, the genetic makeup of the organism, and connectivity in the nervous system to produce extremely diverse adaptations to the phenomenon of existence. Unraveling the subcellular components that contribute to behavioral output is important for both understanding how behavior occurs in an unperturbed state, as well as understanding how behavior changes when the underlying systems that generate it are altered. Of the numerous molecular species that make up a cell, the regulation of messenger RNAs (mRNAs), the coding template of all proteins, is of key importance to …

Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin

Electronic Thesis and Dissertation Repository

The cattle industry worldwide is ravaged by bovine respiratory disease (BRD), a bacterial disease caused by Mannheimia haemolytica. Recent efforts to design vaccines against M. haemolytica focus on a virulence factor, leukotoxin, in addition to surface lipoproteins. Plant-based protein production is a safe and inexpensive alternative to traditional methods. Edible vaccines deliver antigens to pharyngeal tissues, which can provide local immunization against M. haemolytica prior to its progression into the lungs. In this project, a chimeric protein containing M. haemolytica antigens was produced in tobacco chloroplasts as a candidate edible vaccine for BRD. Attempts were made to transform lettuce …

Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu

Doctoral Dissertations

During development, metaphase spindles undergo large movement and/or rotation to determine the cell division axis. While it has been shown that spindle translocation is achieved by astral microtubules pulling and/or pushing the cortex, how metaphase spindle stability is maintained during translocation remains not fully understood. In budding yeast, our lab has previously proposed a model for spindle orientation wherein the mitotic spindle protein She1 promotes spindle translocation across the bud neck by polarizing cortical dynein pulling activity on the astral microtubules. Intriguingly, She1 exhibits dominant spindle localization throughout the cell cycle. However, whether She1 has any additional role on the …

Exploring The Role Of Rna Polymerase Iii Complex Assembly On Ribosomal Dna Silencing In Saccharomyces Cerevisiae, Kyle Thomas Kern

LSU Doctoral Dissertations

The yeast rDNA region is host to a number of transcriptional regulatory elements, which work in conjunction to generate essential RNA subunits of ribosomes, as well as protecting the region from DNA damage. The role of RNA polymerase III complex binding at the 5S gene on rDNA silencing in the NTS2 region was investigated, both by use of a TY1:MET15 reporter insert and a MET15 gene integration at an endogenous SphI site. It was discovered that Pol III complexes do have an effect on reporter expression in the NTS2 region, though the specific effect was different based on the method …

Loss Of Function Of Gene X Protects Against Α-Dicarbonyl Stress Through The Skn-1 Pathway In C. Elegans, Austin Lim

Dissertations, Masters Theses, Capstones, and Culminating Projects

Diabetes mellitus and Parkinson’s Disease (PD) are debilitating diseases that are increasing in prevalence worldwide. One potential cause of these diseases is the accumulation of advanced glycation end products (AGEs), which are macromolecules that cause irreversible damages. AGEs are a diverse group of highly oxidative byproducts produced from α-dicarbonyl compounds (α-dcs), which are highly reactive molecules that bind indiscriminately to protein and DNA and, are regulated by a conserved glyoxalase system (GLO1 and DJ-1) in humans. Utilizing the conserved glyoxalase system, we were able to establish within a C. elegans model that when this glyoxalase system is impaired, …

Integration Of Local And Regional Regulatory Information In The Human Genome, Hemangi Govind Chaudhari

Arts & Sciences Electronic Theses and Dissertations

Gene regulation involves the integration of different sources of information at multiple levels. The action of transcription factors is integrated at cis-regulatory sequences (CRSs). Information from many CRSs is combined to drive spatiotemporally regulated gene expression. Prediction of CRS activity from DNA sequence is challenging because most occurrences of transcription factor binding sites (TFBS) are not functional. I assayed the activity of thousands of genomic sequences with Activator Protein 1 (AP-1) binding sites in K562 cells to identify features in flanking sequences that distinguish functional from non-functional TFBS. I find that sequence features directly adjacent to the AP-1 core motif, …

Novel Approaches To Studying The Effects Of Cis-Regulatory Variants In The Central Nervous System, Susan Shen

Arts & Sciences Electronic Theses and Dissertations

For decades, studies of the genetic basis of disease have focused on rare coding mutations that disrupt protein function, leading to the identification of hundreds of genes underlying Mendelian diseases. However, many complex diseases are non-Mendelian, and less than 2% of the genome is coding. It is now clear that non-coding variants contribute to disease susceptibility, but the precise underlying mechanisms are generally unknown. Cis-regulatory elements (CREs) are transcription factor (TF)-bound genomic regions that regulate gene expression, and variants within CREs can therefore modify gene expression. The putative locations of CREs in a variety of cell types have been identified …

Unravelling The Layers Of Cell Wall Synthesis And Function In Rice, Ritu Mihani

Graduate Theses and Dissertations

The plant cell wall is of critical importance to plant growth and survival, functioning in maintaining structural integrity, supporting cell expansion, and acting as the first line of defense in response to biotic and abiotic stresses. The major components of the cell wall are cellulose, hemicelluloses, lignin, and pectin. Recent focus on the transcriptional machinery regulating cell wall biosynthesis in plants has revealed many key transcription factors responsible for orchestrating cell wall deposition. However, many of these TFs act redundantly and work coherently with a suite of TFs to activate the cell wall biosynthetic machinery. Heterologous expression of TFs is …

Investigation For Novel Anti-Apoptotic Factors In The Neurons Of Drosophila Melanogaster, Haylie Rachel Lam

Chancellor’s Honors Program Projects

No abstract provided.

Optimizing Genetic Manipulation Of Methanogens Through Faster Cloning Techniques, Merrisa Jennings

Biological and Agricultural Engineering Undergraduate Honors Theses

Methanogenesis is the biological production of methane. Only anaerobic archaea known as methanogens are capable of such a metabolic feat. They have strict living conditions and substrate sources which determine their rate of metabolism. This is of particular importance from a greenhouse gas reduction perspective or biogas capturing perspective. One of the best ways to optimize methanogen methane production is via genetic manipulation. The current procedures are timely though, therefore a faster cloning processes should be developed. The objective of this study was to optimize a premade genetic transformation kit known as the Gibson Kit. The Gibson Kit was supposed …

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

Validating Functional Mechanisms For Non-Coding Genetic Variants Associated With Complex Traits, Cynthia Ann Kalita

Wayne State University Dissertations

Genome-wide association studies (GWAS) have identified a large number of genetic variants associated with disease as well as normal phenotypic variation for complex traits. However challenges remain in determining the functional relevance of human DNA sequence variants. Even after fine mapping, most variants are located in non-coding regions making it difficult to infer mechanisms linking individual genetic variants with the disease trait. In addition, we do not know under which environmental conditions the sequence variants have a functional impact, and whether they become one of many factors involved in complex phenotypes at the organismal level.

Chapter 1 describes computational methods …

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …

Role Of Sirna Pathway In Epigenetic Modifications Of The Drosophila Melanogaster X Chromosome, Nikita Deshpande

Wayne State University Dissertations

Eukaryotic genomes are organized into large domains of coordinated regulation. The role of small RNAs in formation of these domains is largely unexplored. An extraordinary example of domain-wide regulation is X chromosome compensation in Drosophila melanogaster males. This process occurs by hypertranscription of genes on the single male X chromosome. Extensive research in this field has shown that the Male Specific Lethal (MSL) complex binds X-linked genes and modifies chromatin to increase expression. The components of this complex, and their actions on chromatin, are well studied. In contrast, the mechanism that results in exclusive recruitment to the X chromosome is …

Role Of Glycerol-3-Phosphate Permeases In Plant Defense, Juliana Moreira Soares

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is a type of plant defense mechanism that is induced after a localized infection and confers broad-spectrum immunity against related or unrelated pathogens. During SAR, a number of chemical signals and proteins generated at the site of primary infection travel to the uninfected tissues and are thought to alert the distal sites against secondary infections. Glycerol-3-phosphate (G3P) is one of the chemical signals that play an important role in SAR. G3P is synthesized in the cytosol and chloroplasts via the enzymatic activities of G3P Dehydrogenase (G3Pdh) or Glycerol Kinase (GK). Interestingly, a mutation in three of …