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Articles 1 - 16 of 16
Full-Text Articles in Molecular Biology
The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou
The Identification Of Small Molecule Inhibitors To Candida Albicans Phosphatidylserine Synthase, Yue Zhou
Doctoral Dissertations
Candida albicans phosphatidylserine (PS) synthase, encoded by the CHO1 gene, has been identified as a potential drug target for new antifungals against systemic candidiasis due to its importance in virulence, absence in the host and conservation among fungal pathogens. This dissertation is focused on the identification of inhibitors for this membrane enzyme. Cho1 has two substrates: cytidyldiphosphate-diacylglycerol (CDP-DAG) and serine. Previous studies identified a conserved CDP-alcohol phosphotransferase (CAPT) binding motif present within Cho1, and here we revealed that mutations in all but one conserved amino acid within the CAPT motif resulted in decreased Cho1. For serine, we have predicted a …
A Shift In Rna Fate: Investigating The Role Of C19orf66 During Kshv Lytic Replication, William Rodriguez Jr.
A Shift In Rna Fate: Investigating The Role Of C19orf66 During Kshv Lytic Replication, William Rodriguez Jr.
Doctoral Dissertations
During viral infection, virus and host clash for control of the cell in a conflict that ultimately drives the evolution of both sides and has lasting consequences in the form of pathogenesis. At the heart of this struggle is a contest for control of cellular gene expression, a struggle epitomized by an evolutionary tug-of-war for supremacy over RNA fate. During lytic replication, Kaposi’s sarcoma-associated herpesvirus (KSHV) triggers a massive RNA decay event known as viral “Host Shutoff” which decimates greater than 70% of the host transcriptome, simultaneously suppressing the cellular anti-viral response and freeing host resources for viral replication. However, …
The Sos Response In Escherichia Coli K12: An Exploration Of Mutations In Lexa And Reca Using Fluorescence Microscopy, Steven Van Alstine
The Sos Response In Escherichia Coli K12: An Exploration Of Mutations In Lexa And Reca Using Fluorescence Microscopy, Steven Van Alstine
Doctoral Dissertations
Faithful replication of the genome is paramount for maintaining the fitness of an organism. Therefore, life has evolved inducible mechanisms to be able to repair damaged DNA and maintain evolutionary fitness. The SOS response is a highly conserved DNA damage inducible response that is tightly regulated. Multiple factors contribute to the ability of the cell to perform proper DNA repair and induction of the SOS response including the amount of RecA, mutations in RecA that affect competition for DNA, and other proteins that interact with the RecA filament. The complex relationship between RecA and LexA is the subject of this …
Mechanisms By Which Xenorhabdus Nematophila Interacts With Hosts Using Integrated -Omics Approaches, Nicholas C. Mucci
Mechanisms By Which Xenorhabdus Nematophila Interacts With Hosts Using Integrated -Omics Approaches, Nicholas C. Mucci
Doctoral Dissertations
Nearly all organisms exist in proximity to microbes. These microbes perform most of the essential metabolic processes necessary for homeostasis, forming the nearly hidden support system of Earth. Microbial symbiosis, which is defined as the long-term physical association between host and microbes, relies on communication between the microbial community and their host organism. These interactions among higher order organisms (such as animals, plants, and fungi) and their bacteria links metabolic processes between interkingdom consortia. Many questions on microbial behavior within a host remain poorly understood, such as the colonization efficiency among different microbial species, or how environmental context changes their …
Microbial Community Dynamics Of A Microcystis Bloom, Helena Pound
Microbial Community Dynamics Of A Microcystis Bloom, Helena Pound
Doctoral Dissertations
Harmful algal bloom events are notoriously associated with massive economic and environmental consequences, causing wildlife and human health risks. As these blooms increase in occurrence, duration, and severity around the world, it is essential to understand conditions leading to bloom formation and why they persist. Abiotic factors such as nutrients are commonly considered in bloom dynamics, but biotic interactions with co-occurring microbial species and viruses must also be taken into account. Harmful algal blooms dominated by the cyanobacterial genus Microcystis occur in bodies of water around the world and provide an ideal system in which to study top-down controls on …
Root Phosphomonoesterase As A Vital Component Of Increasing Phosphorus Availability In Tropical Forests, Kristine Grace Manno Cabugao
Root Phosphomonoesterase As A Vital Component Of Increasing Phosphorus Availability In Tropical Forests, Kristine Grace Manno Cabugao
Doctoral Dissertations
Tropical forests, relative to other terrestrial ecosystems, exchange the largest amount of carbon with the atmosphere and also constitute a significant carbon sink. However, nutrient limitation, particularly of phosphorus (P), could limit growth of tropical forests and their function with the global carbon cycle. Thus, understanding root mechanisms to acquire P is necessary to representing the P cycle and corresponding interactions with plant growth. A large portion of total soil P in tropical forests occurs in organic forms, only accessible through root and microbial production of phosphatase enzymes. These phosphatase enzymes mineralize organic P into orthophosphate, the form of P …
Needles In A Haystack Of Protein Diversity: Interrogation Of Complex Biological Samples Through Specialized Strategies In Bottom-Up Proteomics Uncover Peptides Of Interest For Diverse Applications, Manuel I. Villalobos Solis
Needles In A Haystack Of Protein Diversity: Interrogation Of Complex Biological Samples Through Specialized Strategies In Bottom-Up Proteomics Uncover Peptides Of Interest For Diverse Applications, Manuel I. Villalobos Solis
Doctoral Dissertations
Peptide identification is at the core of bottom-up proteomics measurements. However, even with state-of the-art mass spectrometric instrumentation, peptide level information is still lost or missing in these types of experiments. Reasons behind missing peptide identifications in bottom-up proteomics include variable peptide ionization efficiencies, ion suppression effects, as well as the occurrence of chimeric spectra that can lower the efficacy of database search strategies. Peptides derived from naturally abundant proteins in a biological system also have better chances of being identified in comparison to the ones produced from less abundant proteins, at least in regular discovery-based proteomics experiments. This dissertation …
The Spatial Organization Of Mycobacterial Membrane, Julia Puffal
The Spatial Organization Of Mycobacterial Membrane, Julia Puffal
Doctoral Dissertations
Mycobacteria comprises a large group of organisms including the pathogenic species Mycobacterium tuberculosis, the causative agent of tuberculosis. A fast- growing saprophytic member of this genus, however, Mycobacterium smegmatis, is oftentimes used as a model organism for the pathogenic species. With a unique cell envelope architecture and unconventional polar growth, spatial coordination of cell envelope biosynthesis is vital for proper assembly of this complex structure. Here, we provide a comprehensive overview of known lateral heterogeneities in mycobacterial plasma membrane, with a particular focus on the intracellular membrane domain (IMD), a spatially distinct region of the plasma membrane with diverse functions. …
Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados
Nascent Dna Proteomics Analysis Uncovers Dna Replication Dynamics In The Human Pathogen Trypanosoma Brucei, Maria Rocha Granados
Doctoral Dissertations
DNA is the substrate of many cellular processes including DNA replication, transcription and chromatin remodeling. These processes are coordinated to maintain genome integrity and ensure accurate duplication of genetic and epigenetic information. Genome-wide studies have provided evidence of the relationship between transcription and DNA replication timing. A global analysis of DNA replication initiation in T. brucei showed that TbORC1 (subunit of the origin recognition complex, ORC) binding sites are located at the boundaries of transcription units. Although recent studies in T. brucei indicate functional links among DNA replication and transcription, the underlying mechanisms remain unknown. In this study, we adapted …
Protein Degradation Regulates Phospholipid Biosynthetic Gene Expression In Saccharomyces Cerevisiae, Bryan Salas-Santiago
Protein Degradation Regulates Phospholipid Biosynthetic Gene Expression In Saccharomyces Cerevisiae, Bryan Salas-Santiago
Doctoral Dissertations
Transcriptional regulation of most phospholipid biosynthetic genes in Saccharomyces cerevisiae is coordinated by inositol and choline. Inositol affects phosphatidic acid (PA) intracellular levels. Opi1p interacts physically with PA and is the main repressor of the phospholipid biosynthetic genes. It is localized in the endoplasmic reticulum (ER) bound to the ER membrane protein Scs2p. When PA levels drop, Opi1p is translocated into the nucleus repressing most phospholipid biosynthetic genes. The OPI1 locus was identified in a screen looking for overproduction and excretion of inositol (Opi-). Opi- mutants are generally associated with a defect in …
The Role Of The Metallochaperone Hypa In The Acid Survival And Activities Of Nickel Enzymes In Helicobacter Pylori, Heidi Hu
Doctoral Dissertations
Helicobacter pylori is a bacterium that has colonized the human gastric mucosa of over 50% of the world population. Persistent infection can cause gastritis, peptic ulcers, and cancers. The ability of H. pylori to colonize the acidic environment of the human stomach is dependent on the activity of the nickel containing enzymes, urease and NiFe-hydrogenase. The nickel metallochaperone, HypA, was previously shown to be required for the full activity of both enzymes. In addition to a Ni-binding site, HypA also contains a structural Zn site, which has been characterized to alter its averaged structure depending on pH and the presence …
Regulated Proteolysis Of Dnaa Coordinates Cell Growth With Stress Signals In Caulobacter Crescentus, Jing Liu
Regulated Proteolysis Of Dnaa Coordinates Cell Growth With Stress Signals In Caulobacter Crescentus, Jing Liu
Doctoral Dissertations
DNA replication is an essential process in all domains of life. Replication must be precisely regulated, especially at the step of initiation. In bacteria, the replication initiator DnaA is regulated by multiple post-translational regulations to ensure timely replication. Caulobacter crescentus has the most strict replication regulation that DNA only replicates once per cell cycle, and proteolysis of DnaA identified in this species is the only irreversible way to inhibit DnaA, suggesting it might be pivotal to restricting DNA replication. However, the responsible protease(s) and mechanism for its degradation remain unclear since its first discovery in 2005. In this thesis, I …
The Key Question In Symbiotic Nitrogen Fixation: How Does Host Maintain A Bacterial Symbiont?, Onur Oztas
The Key Question In Symbiotic Nitrogen Fixation: How Does Host Maintain A Bacterial Symbiont?, Onur Oztas
Doctoral Dissertations
The fact that plants cannot use nitrogen in the gaseous form makes them dependent on the levels of usable nitrogen forms in the soil. Legumes overcome nitrogen limitation by entering a symbiotic association with rhizobia, soil bacteria that convert atmospheric nitrogen into usable ammonia. In root nodules, bacteria are internalized by host plant cells inside an intracellular compartment called the symbiosome where they morphologically differentiate into nitrogen-fixing forms by symbiosome-secreted host proteins. In this project, I explained the host proteins required to maintain bacterial symbionts and described their delivery to the symbiosome. I showed that the SYNTAXIN 132 (SYP132) gene …
Control Of Proteolysis During The Caulobacter Cell Cycle, Joanne Lau
Control Of Proteolysis During The Caulobacter Cell Cycle, Joanne Lau
Doctoral Dissertations
Intracellular protein destruction is a carefully coordinated and timed regulatory mechanism that cells utilize to modulate growth, adaptation to environmental cues, and survival. In Caulobacter crescentus, a bacterium known for studies of bacterial cell division cycle, the response regulator CpdR couples phosphorylation events with the AAA+ protease ClpXP to provide punctuated degradation of crucial substrates involved in cell cycle regulation. CpdR functions like an adaptor to alter substrate choice by ClpXP, however it remains unclear how CpdR influences its multiple targets. In this thesis, we show that, unlike canonical ClpXP adaptors, CpdR alone does not strongly bind its substrate. …
Novel Advancements For Improving Sprout Safety, Kyle S. Landry
Novel Advancements For Improving Sprout Safety, Kyle S. Landry
Doctoral Dissertations
All varieties of bean sprouts (mung bean, alfalfa, broccoli, and radish) are classified as a “super-food” and are common staples for health conscious consumers. Along with the proposed health benefits, there is also an inherent risk of foodborne illness. When sprouts are cooked, there is little risk of illness. The purpose of this dissertation was to explore novel techniques to minimize or prevent the incidence of foodborne illness associated with the consumption of sprouts. Three areas were investigated: 1) the use of a biocontrol organism, 2) the use of a novel spontaneous carvacrol nanoemulsion, and 3) the influence of the …
Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood
Comparative Genomics Of Microbial Chemoreceptor Sequence, Structure, And Function, Aaron Daniel Fleetwood
Doctoral Dissertations
Microbial chemotaxis receptors (chemoreceptors) are complex proteins that sense the external environment and signal for flagella-mediated motility, serving as the GPS of the cell. In order to sense a myriad of physicochemical signals and adapt to diverse environmental niches, sensory regions of chemoreceptors are frenetically duplicated, mutated, or lost. Conversely, the chemoreceptor signaling region is a highly conserved protein domain. Extreme conservation of this domain is necessary because it determines very specific helical secondary, tertiary, and quaternary structures of the protein while simultaneously choreographing a network of interactions with the adaptor protein CheW and the histidine kinase CheA. This dichotomous …