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This dissertation is presented in two sections. First, I explore two methods of using stable isotope analysis to trace environmental and biogeochemical processes. Second, I present two related studies investigating student understanding of the biogeochemical concepts that underlie part one. Fe and Hg are each biogeochemically important elements in their own way. Fe is a critical nutrient for phytoplankton, while Hg is detrimental to nearly all forms of life. Fe is often a limiting factor in marine phytoplankton growth. The largest source, by mass, of Fe to the open ocean is windblown mineral dust, but other more soluble sources are more bioavailable. To look for evidence of these non-soil dust sources of Fe to the open ocean, I measured the isotopic composition of aerosol samples collected on Bermuda. I found clear evidence in the fine size fraction of a non-soil dust Fe source, which I conclude is most likely from biomass burning. Widespread adoption of compact fluorescent lamps (CFL) has increased their importance as a source of environmental Hg. Isotope analysis would be a useful tool in quantifying this impact if the isotopic composition of Hg from CFL were known. My measurements show that CFL-Hg is isotopically fractionated, in a unique pattern, during normal operation. This fractionation is large and has a distinctive, mass-independent signature, such that CFL Hg can be uniquely identified from other sources. Misconceptions research in geology has been a very active area of research, but student thinking regarding the related field of biogeochemistry has not yet been studied in detail. From interviews with 40 undergraduates, I identified over 150 specific misconceptions. I also designed a multiple-choice survey (concept inventory) to measure understanding of these same biogeochemistry concepts. I present statistical evidence, based on the Rasch model, for the reliability and validity of this instrument. This instrument will allow teachers and researchers to easily quantify learning outcomes in biogeochemistry and will complement existing concept inventories in geology, chemistry, and biology.
ContributorsMead, Chris (Author) / Anbar, Ariel (Thesis advisor) / Semken, Steven (Committee member) / Shock, Everett (Committee member) / Herckes, Pierre (Committee member) / Hartnett, Hilairy (Committee member) / Arizona State University (Publisher)
Created2014
Description
Telomerase enzyme is a truly remarkable enzyme specialized for the addition of short, highly repetitive DNA sequences onto linear eukaryotic chromosome ends. The telomerase enzyme functions as a ribonucleoprotein, minimally composed of the highly conserved catalytic telomerase reverse transcriptase and essential telomerase RNA component containing an internalized short template region within the vastly larger non-coding RNA. Even among closely related groups of species, telomerase RNA is astonishingly divergent in sequence, length, and secondary structure. This massive disparity is highly prohibitive for telomerase RNA identification from previously unexplored groups of species, which is fundamental for secondary structure determination. Combined biochemical enrichment and computational screening methods were employed for the discovery of numerous telomerase RNAs from the poorly characterized echinoderm lineage. This resulted in the revelation that--while closely related to the vertebrate lineage and grossly resembling vertebrate telomerase RNA--the echinoderm telomerase RNA central domain varies extensively in structure and sequence, diverging even within echinoderms amongst sea urchins and brittle stars. Furthermore, the origins of telomerase RNA within the eukaryotic lineage have remained a persistent mystery. The ancient Trypanosoma telomerase RNA was previously identified, however, a functionally verified secondary structure remained elusive. Synthetic Trypanosoma telomerase was generated for molecular dissection of Trypanosoma telomerase RNA revealing two RNA domains functionally equivalent to those found in known telomerase RNAs, yet structurally distinct. This work demonstrates that telomerase RNA is uncommonly divergent in gross architecture, while retaining critical universal elements.
ContributorsPodlevsky, Joshua (Author) / Chen, Julian (Thesis advisor) / Mangone, Marco (Committee member) / Kusumi, Kenro (Committee member) / Wilson-Rawls, Norma (Committee member) / Arizona State University (Publisher)
Created2015
Description
In enzyme induced carbonate precipitation (EICP), calcium carbonate (CaCO3) precipitation is catalyzed by plant-derived urease enzyme. In EICP, urea hydrolyzes into ammonia and inorganic carbon, altering geochemical conditions in a manner that promotes carbonate mineral precipitation. The calcium source in this process comes from calcium chloride (CaCl2) in aqueous solution. Research work conducted for this dissertation has demonstrated that EICP can be employed for a variety of geotechnical purposes, including mass soil stabilization, columnar soil stabilization, and stabilization of erodible surficial soils. The research presented herein also shows that the optimal ratio of urea to CaCl2 at ionic strengths of less than 1 molar is approximately 1.75:1. EICP solutions of very high initial ionic strength (i.e. 6 M) as well as high urea concentrations (> 2 M) resulted in enzyme precipitation (salting-out) which hindered carbonate precipitation. In addition, the production of NH4+ may also result in enzyme precipitation. However, enzyme precipitation appeared to be reversible to some extent. Mass soil stabilization was demonstrated via percolation and mix-and-compact methods using coarse silica sand (Ottawa 20-30) and medium-fine silica sand (F-60) to produce cemented soil specimens whose strength improvement correlated with CaCO3 content, independent of the method employed to prepare the specimen. Columnar stabilization, i.e. creating columns of soil cemented by carbonate precipitation, using Ottawa 20-30, F-60, and native AZ soil was demonstrated at several scales beginning with small columns (102-mm diameter) and culminating in a 1-m3 soil-filled box. Wind tunnel tests demonstrated that surficial soil stabilization equivalent to that provided by thoroughly wetting the soil can be achieved through a topically-applied solution of CaCl2, urea, and the urease enzyme. The topically applied solution was shown to form an erosion-resistant CaCO3 crust on fine sand and silty soils. Cementation of erodible surficial soils was also achieved via EICP by including a biodegradable hydrogel in the stabilization solution. A dilute hydrogel solution extended the time frame over which the precipitation reaction could occur and provided improved spatial control of the EICP solution.
ContributorsHamdan, Nasser M (Author) / Kavazanjian Jr., Edward (Thesis advisor) / Rittmann, Bruce (Thesis advisor) / Shock, Everett (Committee member) / Arizona State University (Publisher)
Created2015
Description
The taxonomic and metabolic profile of the microbial community inhabiting a natural system is largely determined by the physical and geochemical properties of the system. However, the influences of parameters beyond temperature, pH and salinity have been poorly analyzed with few studies incorporating the comprehensive suite of physical and geochemical measurements required to fully investigate the complex interactions known to exist between biology and the environment. Further, the techniques used to classify the taxonomic and functional composition of a microbial community are fragmented and unwieldy, resulting in unnecessarily complex and often non-consilient results.
This dissertation integrates environmental metagenomes with extensive geochemical metadata for the development and application of multidimensional biogeochemical metrics. Analysis techniques including a Markov cluster-based evolutionary distance between whole communities, oligonucleotide signature-based taxonomic binning and principal component analysis of geochemical parameters allow for the determination of correlations between microbial community dynamics and environmental parameters. Together, these techniques allow for the taxonomic classification and functional analysis of the evolution of hot spring communities. Further, these techniques provide insight into specific geochemistry-biology interactions which enable targeted analyses of community taxonomic and functional diversity. Finally, analysis of synonymous substitution rates among physically separated microbial communities provides insights into microbial dispersion patterns and the roles of environmental geochemistry and community metabolism on DNA transfer among hot spring communities.
The data presented here confirms temperature and pH as the primary factors shaping the evolutionary trajectories of microbial communities. However, the integration of extensive geochemical metadata reveals new links between geochemical parameters and the distribution and functional diversification of communities. Further, an overall geochemical gradient (from multivariate analyses) between natural systems provides one of the most complete predictions of microbial community functional composition and inter-community DNA transfer rates. Finally, the taxonomic classification and clustering techniques developed within this dissertation will facilitate future genomic and metagenomic studies through enhanced community profiling obtainable via Markov clustering, longer oligonucleotide signatures and insight into PCR primer biases.
This dissertation integrates environmental metagenomes with extensive geochemical metadata for the development and application of multidimensional biogeochemical metrics. Analysis techniques including a Markov cluster-based evolutionary distance between whole communities, oligonucleotide signature-based taxonomic binning and principal component analysis of geochemical parameters allow for the determination of correlations between microbial community dynamics and environmental parameters. Together, these techniques allow for the taxonomic classification and functional analysis of the evolution of hot spring communities. Further, these techniques provide insight into specific geochemistry-biology interactions which enable targeted analyses of community taxonomic and functional diversity. Finally, analysis of synonymous substitution rates among physically separated microbial communities provides insights into microbial dispersion patterns and the roles of environmental geochemistry and community metabolism on DNA transfer among hot spring communities.
The data presented here confirms temperature and pH as the primary factors shaping the evolutionary trajectories of microbial communities. However, the integration of extensive geochemical metadata reveals new links between geochemical parameters and the distribution and functional diversification of communities. Further, an overall geochemical gradient (from multivariate analyses) between natural systems provides one of the most complete predictions of microbial community functional composition and inter-community DNA transfer rates. Finally, the taxonomic classification and clustering techniques developed within this dissertation will facilitate future genomic and metagenomic studies through enhanced community profiling obtainable via Markov clustering, longer oligonucleotide signatures and insight into PCR primer biases.
ContributorsAlsop, Eric Bennie (Author) / Raymond, Jason (Thesis advisor) / Anbar, Ariel (Committee member) / Farmer, Jack (Committee member) / Shock, Everett (Committee member) / Walker, Sarah (Committee member) / Arizona State University (Publisher)
Created2014
Description
MicroRNAs (miRNAs) are short non-coding RNAs that play key roles during metazoan development, and are frequently misregulated in human disease. MiRNAs regulate gene output by targeting degenerate elements primarily in the 3´ untranslated regions of mRNAs. MiRNAs are often deeply conserved, but have undergone drastic expansions in higher metazoans, leading to families of miRNAs with highly similar sequences. The evolutionary advantage of maintaining multiple copies of duplicated miRNAs is not well understood, nor has the distinct functions of miRNA family members been systematically studied. Furthermore, the unbiased and high-throughput discovery of targets remains a major challenge, yet is required to understand the biological function of a given miRNA.
I hypothesize that duplication events grant miRNA families with enhanced regulatory capabilities, specifically through distinct targeting preferences by family members. This has relevance for our understanding of vertebrate evolution, as well disease detection and personalized medicine. To test this hypothesis, I apply a conjunction of bioinformatic and experimental approaches, and design a novel high-throughput screening platform to identify human miRNA targets. Combined with conventional approaches, this tool allows systematic testing for functional targets of human miRNAs, and the identification of novel target genes on an unprecedented scale.
In this dissertation, I explore evolutionary signatures of 62 deeply conserved metazoan miRNA families, as well as the targeting preferences for several human miRNAs. I find that constraints on miRNA processing impact sequence evolution, creating evolutionary hotspots within families that guide distinct target preferences. I apply our novel screening platform to two cancer-relevant miRNAs, and identify hundreds of previously undescribed targets. I also analyze critical features of functional miRNA target sites, finding that each miRNA recognizes surprisingly distinct features of targets. To further explore the functional distinction between family members, I analyze miRNA expression patterns in multiple contexts, including mouse embryogenesis, RNA-seq data from human tissues, and cancer cell lines. Together, my results inform a model that describes the evolution of metazoan miRNAs, and suggests that highly similar miRNA family members possess distinct functions. These findings broaden our understanding of miRNA function in vertebrate evolution and development, and how their misexpression contributes to human disease.
I hypothesize that duplication events grant miRNA families with enhanced regulatory capabilities, specifically through distinct targeting preferences by family members. This has relevance for our understanding of vertebrate evolution, as well disease detection and personalized medicine. To test this hypothesis, I apply a conjunction of bioinformatic and experimental approaches, and design a novel high-throughput screening platform to identify human miRNA targets. Combined with conventional approaches, this tool allows systematic testing for functional targets of human miRNAs, and the identification of novel target genes on an unprecedented scale.
In this dissertation, I explore evolutionary signatures of 62 deeply conserved metazoan miRNA families, as well as the targeting preferences for several human miRNAs. I find that constraints on miRNA processing impact sequence evolution, creating evolutionary hotspots within families that guide distinct target preferences. I apply our novel screening platform to two cancer-relevant miRNAs, and identify hundreds of previously undescribed targets. I also analyze critical features of functional miRNA target sites, finding that each miRNA recognizes surprisingly distinct features of targets. To further explore the functional distinction between family members, I analyze miRNA expression patterns in multiple contexts, including mouse embryogenesis, RNA-seq data from human tissues, and cancer cell lines. Together, my results inform a model that describes the evolution of metazoan miRNAs, and suggests that highly similar miRNA family members possess distinct functions. These findings broaden our understanding of miRNA function in vertebrate evolution and development, and how their misexpression contributes to human disease.
ContributorsWolter, Justin M (Author) / Mangone, Marco (Thesis advisor) / LaBaer, Joshua (Committee member) / Kusumi, Kenro (Committee member) / Anderson, Karen (Committee member) / Arizona State University (Publisher)
Created2016
Description
One goal of geobiochemistry is to follow geochemical energy supplies from the external environment to the inside of microbial cells. This can be accomplished by combining thermodynamic calculations of energy supplies from geochemical processes and energy demands for biochemical processes. Progress towards this goal is summarized here. A critique of all thermodynamic data for biochemical compounds involved in the citric acid cycle (CAC) and the formulation of metabolite properties allows predictions of the energy involved in each step of the cycle as well as the full forward and reverse cycles over wide ranges of temperature and pressure. These results allow evaluation of energy demands at the center of many microbial metabolic systems. Field work, sampling, and lab analyses from two low-temperature systems, a serpentinizing system, and a subglacial setting, provide the data used in these thermodynamic analyses of energy supplies. An extensive literature summary of microbial and molecular data from serpentinizing systems found is used to guide the evaluation and ranking of energy supplies used by chemolithoautotrophic microbes. These results constrain models of the distribution of microbial metabolisms throughout the low-temperature serpentinization systems in the Samail ophiolite in Oman (including locales of primary and subsequent alteration processes). Data collected from Robertson Glacier in Alberta, Canada, together with literature data from Lake Vida in Antarctica and bottom seawater, allowed thermodynamic analyses of low-temperature energy supplies in a glacial system. Results for 1460 inorganic redox reactions are used to fully inventory the geochemical energy sources that support the globally extensive cold biosphere.
ContributorsCanovas, Peter Anthony (Author) / Shock, Everett (Thesis advisor) / Hartnett, Hilairy (Committee member) / Sharp, Thomas (Committee member) / Tyburczy, James (Committee member) / Heimsath, Arjun (Committee member) / Arizona State University (Publisher)
Created2016
Hydrothermal reactions of organic compounds in the presence of minerals: a study of carboxylic acids
Description
Carboxylic acids are an abundant and reactive species present throughout our solar system. The reactions of carboxylic acids can shape the organic abundances within oil field brines, carbonaceous chondrites, and different ranks of coal.
I have performed hydrothermal experiments with model aromatic carboxylic acids in the presences of different oxide minerals to investigate the reactions available to carboxylic acids in the presence of mineral surfaces. By performing experiments containing one organic compound and one mineral surface, I can begin to unravel the different reactions that can occur in the presence of different minerals.
I performed experiments with phenylacetic acid (PAA), hydrocinnamic acid (HCA) and benzoic acid (BA) in the presence of spinel (MgAl2O4), magnetite (Fe3O4), hematite (Fe2O3), and corundum (Al2O3). The focus of this work was metal oxide minerals, with and without transition metal atoms, and with different crystal structures. I found that all four oxide minerals facilitated ketonic decarboxylation reactions of carboxylic acids to form ketone structures. The two minerals containing transition metals (magnetite and hematite) also opened a reaction path involving electrochemical oxidation of one carboxylic acid, PAA, to the shorter chain version of a second carboxylic acid, BA, in experiments starting with PAA. Fundamental studies like these can help to shape our knowledge of the breadth of organic reactions that are possible in geologic systems and the mechanisms of those reactions.
I have performed hydrothermal experiments with model aromatic carboxylic acids in the presences of different oxide minerals to investigate the reactions available to carboxylic acids in the presence of mineral surfaces. By performing experiments containing one organic compound and one mineral surface, I can begin to unravel the different reactions that can occur in the presence of different minerals.
I performed experiments with phenylacetic acid (PAA), hydrocinnamic acid (HCA) and benzoic acid (BA) in the presence of spinel (MgAl2O4), magnetite (Fe3O4), hematite (Fe2O3), and corundum (Al2O3). The focus of this work was metal oxide minerals, with and without transition metal atoms, and with different crystal structures. I found that all four oxide minerals facilitated ketonic decarboxylation reactions of carboxylic acids to form ketone structures. The two minerals containing transition metals (magnetite and hematite) also opened a reaction path involving electrochemical oxidation of one carboxylic acid, PAA, to the shorter chain version of a second carboxylic acid, BA, in experiments starting with PAA. Fundamental studies like these can help to shape our knowledge of the breadth of organic reactions that are possible in geologic systems and the mechanisms of those reactions.
ContributorsJohnson, Kristin Nicole (Author) / Shock, Everett (Thesis advisor) / Hartnett, Hilairy (Committee member) / Gould, Ian (Committee member) / Arizona State University (Publisher)
Created2017
Description
Lipids perform functions essential to life and have a variety of structures that are influenced by the organisms and environments that produced them. Lipids tend to resist degradation after cell death, leading to their widespread use as biomarkers in geobiology, though their interpretation is often tricky. Many lipid structures are shared among organisms and function in many geochemical conditions and extremes. I argue it is useful to interpret lipid distributions as a balance of functional necessity and energy cost. This work utilizes a quantitative thermodynamic framework for interpreting energetically driven adaptation in lipids.
Yellowstone National Park is a prime location to study biological adaptations to a wide range of temperatures and geochemical conditions. Lipids were extracted and quantified from thermophilic microbial communities sampled along the temperature (29-91°C) and chemical gradients of four alkaline Yellowstone hot springs. I observed that decreased alkyl chain carbon content, increased degree of unsaturation, and a shift from ether to ester linkage caused a downstream increase in the average oxidation state of carbon (ZC) I hypothesized these adaptations were selected because they represent cost-effective solutions to providing thermostable membranes.
This hypothesis was explored by assessing the relative energetic favorability of autotrophic reactions to form alkyl chains from known concentrations of dissolved inorganic species at elevated temperatures. I found that the oxidation-reduction potential (Eh) predicted to favor formation of sample-representative alkyl chains had a strong positive correlation with Eh calculated from hot spring water chemistry (R2 = 0.72 for the O2/H2O redox couple). A separate thermodynamic analysis of bacteriohopanepolyol lipids found that predicted equilibrium abundances of observed polar headgroup distributions were also highly correlated with Eh of the surrounding water (R2= 0.84). These results represent the first quantitative thermodynamic assessment of microbial lipid adaptation in natural systems and suggest that observed lipid distributions represent energetically cost-effective assemblages along temperature and chemical gradients.
Yellowstone National Park is a prime location to study biological adaptations to a wide range of temperatures and geochemical conditions. Lipids were extracted and quantified from thermophilic microbial communities sampled along the temperature (29-91°C) and chemical gradients of four alkaline Yellowstone hot springs. I observed that decreased alkyl chain carbon content, increased degree of unsaturation, and a shift from ether to ester linkage caused a downstream increase in the average oxidation state of carbon (ZC) I hypothesized these adaptations were selected because they represent cost-effective solutions to providing thermostable membranes.
This hypothesis was explored by assessing the relative energetic favorability of autotrophic reactions to form alkyl chains from known concentrations of dissolved inorganic species at elevated temperatures. I found that the oxidation-reduction potential (Eh) predicted to favor formation of sample-representative alkyl chains had a strong positive correlation with Eh calculated from hot spring water chemistry (R2 = 0.72 for the O2/H2O redox couple). A separate thermodynamic analysis of bacteriohopanepolyol lipids found that predicted equilibrium abundances of observed polar headgroup distributions were also highly correlated with Eh of the surrounding water (R2= 0.84). These results represent the first quantitative thermodynamic assessment of microbial lipid adaptation in natural systems and suggest that observed lipid distributions represent energetically cost-effective assemblages along temperature and chemical gradients.
ContributorsBoyer, Grayson Maxwell (Author) / Shock, Everett (Thesis advisor) / Hartnett, Hilairy (Committee member) / Herckes, Pierre (Committee member) / Arizona State University (Publisher)
Created2018
Description
Volcanic eruptions can be serious geologic hazards, and have the potential to effect human life, infrastructure, and climate. Therefore, an understanding of the evolution and conditions of the magmas stored beneath volcanoes prior to their eruption is crucial for the ability to monitor such systems and develop effective hazard mitigation plans. This dissertation combines classic petrologic tools such as mineral chemistry and thermometry with novel techniques such as diffusion chronometry and statistical modeling in order to better understand the processes and timing associated with volcanic eruptions. By examining zoned crystals from the fallout ash of Yellowstone’s most recent supereruption, my work shows that the rejuvenation of magma has the ability to trigger a catastrophic supereruption at Yellowstone caldera in the years (decades at most) prior to eruption. This provides one of the first studies to thoroughly identify a specific eruption trigger of a past eruption using the crystal record. Additionally, through experimental investigation, I created a novel diffusion chronometer with application to determine magmatic timescales in silicic volcanic systems (i.e., rhyolite/dacite). My results show that Mg-in-sanidine diffusion operates simultaneously by both a fast and slow diffusion path suggesting that experimentally-derived diffusion chronometers may be more complex than previously thought. When applying Mg-in-sanidine chronometry to zoned sanidine from the same supereruption at Yellowstone, the timing between rejuvenation and eruption is further resolved to as short as five months, providing a greater understanding of the timing of supereruption triggers. Additionally, I developed a new statistical model to examine the controls on a single volcano’s distribution of eruptions through time, therefore the controls on the timing between successive eruptions, or repose time. When examining six Cascade volcanoes with variable distribution patterns through time, my model shows these distributions are not result of sampling bias, rather may represent geologic processes. There is a robust negative correlation between average repose time and average magma composition (i.e., SiO2), suggesting this may be a controlling factor of long-term repose time at Cascade volcanoes. Together, my work provides a better vision for forecasting models to mitigate potential destruction.
ContributorsShamloo, Hannah (Author) / Till, Christy (Thesis advisor) / Hervig, Richard (Committee member) / Barboni, Melanie (Committee member) / Shock, Everett (Committee member) / Shim, Sang-Heon (Committee member) / Arizona State University (Publisher)
Created2020
Description
Duchenne muscular dystrophy (DMD) is a lethal, X-linked disease characterized by progressive muscle degeneration. The condition is driven by out-of-frame mutations in the dystrophin gene, and the absence of a functional dystrophin protein ultimately leads to instability of the sarcolemma, skeletal muscle necrosis, and atrophy. While the structural changes that occur in dystrophic muscle are well characterized, resulting changes in muscle-specific gene expression that take place in dystrophin’s absence remain largely uncharacterized, as they are potentially obscured by the characteristic chronic inflammation in dystrophin deficient muscle.
The conservation of the dystrophin gene across metazoans suggests that both vertebrate and invertebrate model systems can provide valuable contributions to the understanding of DMD initiation and progression. Specifically, the invertebrate C. elegans possesses a dystrophin protein ortholog, dys-1, and a mild inflammatory response that is inactive in the muscle, allowing for the characterization of transcriptome rearrangements affecting disease progression independently of inflammation. Furthermore, C. elegans do not possess a satellite cell equivalent, meaning muscle regeneration does not occur. This makes C. elegans unique in that they allow for the study of dystrophin deficiencies without muscle regeneration that may obscure detection of subtle but consequential changes in gene expression.
I hypothesize that gaining a comprehensive definition of both the structural and signaling roles of dystrophin in C. elegans will improve the community’s understanding of the progression of DMD as a whole. To address this hypothesis, I have performed a phylogenetic analysis on the conservation of each member of the dystrophin associated protein complex (DAPC) across 10 species, established an in vivo system to identify muscle-specific changes in gene expression in the dystrophin-deficient C. elegans, and performed a functional analysis to test the biological significance of changes in gene expression identified in my sequencing results. The results from this study indicate that in C. elegans, dystrophin may have a signaling role early in development, and its absence may activate compensatory mechanisms that counteract disease progression. Furthermore, these findings allow for the identification of transcriptome changes that potentially serve as both independent drivers of disease and potential therapeutic targets for the treatment of DMD.
The conservation of the dystrophin gene across metazoans suggests that both vertebrate and invertebrate model systems can provide valuable contributions to the understanding of DMD initiation and progression. Specifically, the invertebrate C. elegans possesses a dystrophin protein ortholog, dys-1, and a mild inflammatory response that is inactive in the muscle, allowing for the characterization of transcriptome rearrangements affecting disease progression independently of inflammation. Furthermore, C. elegans do not possess a satellite cell equivalent, meaning muscle regeneration does not occur. This makes C. elegans unique in that they allow for the study of dystrophin deficiencies without muscle regeneration that may obscure detection of subtle but consequential changes in gene expression.
I hypothesize that gaining a comprehensive definition of both the structural and signaling roles of dystrophin in C. elegans will improve the community’s understanding of the progression of DMD as a whole. To address this hypothesis, I have performed a phylogenetic analysis on the conservation of each member of the dystrophin associated protein complex (DAPC) across 10 species, established an in vivo system to identify muscle-specific changes in gene expression in the dystrophin-deficient C. elegans, and performed a functional analysis to test the biological significance of changes in gene expression identified in my sequencing results. The results from this study indicate that in C. elegans, dystrophin may have a signaling role early in development, and its absence may activate compensatory mechanisms that counteract disease progression. Furthermore, these findings allow for the identification of transcriptome changes that potentially serve as both independent drivers of disease and potential therapeutic targets for the treatment of DMD.
ContributorsHrach, Heather (Author) / Mangone, Marco (Thesis advisor) / LaBaer, Joshua (Committee member) / Newbern, Jason (Committee member) / Rawls, Jeffery (Committee member) / Arizona State University (Publisher)
Created2020