Theses and Dissertations at Montana State University (MSU)
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Item Genetic dissection of malt quality in barley: an examination of hydration index and metabolite QTL(Montana State University - Bozeman, College of Agriculture, 2024) Jensen, Joseph Riley; Chairperson, Graduate Committee: Jamie Sherman; This is a manuscript style paper that includes co-authored chapters.Malting barley is a high value crop for American farmers. Through the malting process grain is turned into malt which is primarily used in brewing but can also be a flavor and nutritional additive for the food industry. During the malting process hydration of the endosperm is a rate limiting step resulting in increased time and water usage if a third water immersion is needed during steeping. To better understand the genetics of endosperm hydration we used a genome wide association (GWAS) population to map quantitative trait loci (QTL) for malt quality, hydration index (endosperm hydration), and seed morphology traits. We found six hydration index QTL with three related to seed size (qHYI1H, qHYI3H.a, and qHYI3H.b), two improving malt quality (qHYI2H and qHYI6H), and the last (qHYI7H) wasn't related to any other traits. We then wanted to see the relationship between hydration index and dormancy because dormancy is needed to prevent preharvest sprouting. Preharvest sprouting in malt barley results in extreme price reductions for producers however the dormancy genes needed to prevent this negatively impact malt quality. Using a biparental mapping population we were able to map two hydration index QTL and relate them to the dormancy gene SD2. Our results confirmed SD2 negatively impacts malt quality but when the positive alleles for hydration index are present, they negate dormancy's negative effects on quality. The results from these two studies show hydration index can benefit growers and maltsters with barley and malt production. Our third study looked at metabolite variation in the GWAS population to see if we could identify QTL related to malt flavor. This would help craft malt houses and breweries which are usually in search of unique flavors. We were able to identify 827 metabolite QTL however the most impactful to flavor were amino acid, saccharide, and maltol QTL which totaled 39. The three maltol QTL which are directly related to flavor all co-located with maltol precursors (amino acids and saccharides) showing these QTL would be good targets for marker assisted selection to create maltol variation.Item Investigations of the gut-brain-metabolism axis in familial dysautonomia(Montana State University - Bozeman, College of Letters & Science, 2023) Cheney, Alexandra Marie; Co-chairs, Graduate Committee: Frances Lefcort; Valerie Copie; This is a manuscript style paper that includes co-authored chapters.Familial dysautonomia (FD), a neurodevelopmental and neurodegenerative disease primarily present in Eastern European Jewish populations, is a useful model system to explore the effects of neuronal dysregulation, particularly in the developing field of the gut-brain-metabolism axis. FD originates from a single genetic mutation in the ELP1 gene and differs from other neurological diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and autism that are dependent on multiple factors. Metabolic and gut impairments have been observed in FD patients, but only symptom management has been pursued without further exploration into the underlying disease pathophysiology. To better understand how the gut environment changes as a result of neuronal dysregulation and how this impacts the gut-brain-metabolism axis in FD patients, several studies of both human and FD mouse model samples were undertaken. Serum and stool samples from FD patients and their relatives were analyzed for metabolic alterations using proton nuclear magnetic resonance (1H NMR)-based metabolomics. Stool samples from both a human cohort and FD mice were also analyzed for gut bacterial diversity via 16S rRNA gene sequencing. Additionally, stool metabolomes of FD mice were analyzed for metabolic alterations. The FD mouse model enabled us to explore how gut physiology changed during disease progression using gut histological methods and gut function assays. Our studies demonstrated significant changes in the metabolomes and gut microbiomes of FD patients compared to their healthy relative controls. Additionally, the FD mouse model, a pan-neuronal Elp1 conditional knock out, was sufficient to drive metabolic and gut microbiome changes, and impair gut barrier function compared to control mice. When FD mice cohabitated with healthy control mice and were able to exchange gut microbes via stool consumption, the cohoused FD mice improved in overall health and gut function. Our studies found that the gut microbiome and metabolome of cohoused FD mice were comparable to their cohoused control counterparts. Overall, this work has enhanced our understanding of the gut-brain-metabolism axis in Familial dysautonomia and has provided insights into underlying molecular mechanisms, which may be potential targets for therapeutic interventions, including the use of metabolic supplements and/or altering the gut microbiome.Item Characterization of osteoarthritis metabolism: a mass spectrometry based-approach(Montana State University - Bozeman, College of Letters & Science, 2024) Welhaven, Hope Diane Aloha; Co-chairs, Graduate Committee: Brian Bothner and Ronald K. June II; This is a manuscript style paper that includes co-authored chapters.Osteoarthritis (OA) effects 7% of the global population, equating to more than 500 million people worldwide, and is the leading cause of disability. Its multifaceted etiology includes risk factors ranging from genetics, to aging, obesity, sex, race, and joint injury. OA manifests differently across the patient population where symptom severity, rate of progression, response to treatment, pain perception, as well as others vary person to person posing significant challenges for effective management and prevention. At the cellular level, imbalanced matrix catabolism and anabolism contribute to the breakdown of cartilage, underlying bone, and other tissues affected by OA. Leveraging mass spectrometry-based techniques, particularly metabolomics, offers a promising avenue to dissect OA metabolism across musculoskeletal tissues, while considering individual patient-specific risk factors. Therefore, the goals of this research were to: (1) comprehensively characterize OA phenotypes and endotypes and (2) explore OA pathogenesis within the context of disease-associated risk factors. The first area of research focuses on profiling OA phenotypes and endotypes across disease development. These results provide clear evidence of OA-induced metabolic perturbations in OA cartilage and bone and elucidate mechanisms that shift as disease progresses. Several metabolites and pathways associated with lipid, amino acid, matrix, and vitamin metabolism were differentially regulated between healthy and OA tissues and within OA endotypes. The second area of research focuses on the impact of OA risk factors -- sex, injury, obesity, loading -- on the metabolism of circulatory fluids (i.e., serum, synovial fluid) and chondrocytes. Identification of metabolic indicators of disease, such as cervonyl carnitine, and metabolic pathways associated with these risk factors holds potential for improving screening, monitoring disease progression, and guiding preventative strategies. Overall, this work contributes to our current understanding of OA, its diverse metabolic landscape, risk factors and their interactions. Moreover, it lays the groundwork for personalized medicine by providing detailed insights into individualized phenotypic profiles, thereby advancing the prospect of tailored treatment strategies for OA individuals.Item The relationship between physiological stress response and variation in omics data(Montana State University - Bozeman, College of Letters & Science, 2021) Steward, Katherine Fay; Chairperson, Graduate Committee: Brian Bothner; This is a manuscript style paper that includes co-authored chapters.Omics analysis is the cornerstone of systems biology. It offers comprehensive assessments of stress, interaction networks and connections to phenotype. Defining a stressed phenotype can be challenging, however, as stress response mechanisms can arise from a range of environmental conditions and experimental perturbations. Previous work from our lab noted the possibility of a relationship between stress in omics data and the variation of that data. This connection has yet to be clearly defined, and the cellular mechanisms responsible for the canalization of omics data remain a mystery. In this work I have taken advantage of the sensitivity of metabolomics and proteomics to detect cellular stress and characterize its relationship to variation. By utilizing coefficient of variation (CV) as a statistic of merit, the depth of the relationship between stress and variation can be uncovered. Once the model was clearly defined, a proteomics dataset with a large proportion of protein coverage was utilized to investigate what pathways might be responsible for the metabolite and protein canalization.Item Quantitative 1 H NMR analyses of immunometabolic modulation in human macrophages(Montana State University - Bozeman, College of Letters & Science, 2019) Fuchs, Amanda Lee; Chairperson, Graduate Committee: Valerie Copie; Sage M. Schiller was an author and Wyatt J. Keegan, Mary Cloud B. Ammons, Brian Eilers, Brian Tripet and Valerie Copie were co-authors of the article, 'Quantitative 1 H NMR metabolomics reveals distinct metabolic adaptations in human macrophages following differential activation' in the journal 'Metabolites' which is contained within this dissertation.; Sage M. Schiller was an author and Isaac R. Miller, Mary Cloud B. Ammons, Brian Eilers, Brian Tripet and Valerie Copie were co-authors of the article, 'Pseudomonas aeruginosa planktonic- and biofilm-conditioned media elicit divergent responses in human macrophages' submitted to the journal 'PLoS pathogens' which is contained within this dissertation.Macrophages are innate immune cells that are found ubiquitously in nearly all human tissues, where they support host innate and adaptive immune responses in an effort to maintain systemic homeostasis. They are inherently plastic in nature and can dramatically modulate their functional phenotype according to pathogen and microenvironmental stimuli. Previous studies have shown that macrophages are particularly important for the resolution of inflammation in acute wound healing, which is marked by a phenotypic transition of wound macrophages from pro-inflammatory to anti-inflammatory. Chronic, or non-healing, wounds, such as diabetic, pressure, and venous leg ulcers, feature a prolonged host inflammatory response due in part to aberrant wound macrophage behavior. Non-healing in chronic wounds has also been shown to be dependent upon the establishment of pathogenic biofilms, which are more resistant to host defense mechanisms than planktonic, or free-floating, bacteria. Therefore, investigating macrophage dysregulation in the presence of bacterial biofilms has gained considerable interest. Here, 1D 1 H NMR-based metabolomics was utilized to identify metabolic pathways that are differentially modulated following primary human monocyte-derived macrophage activation with pro-inflammatory or anti-inflammatory stimuli relative to resting macrophages. Metabolic profiling of inflammatory macrophages indicated a substantial increase in oxidative stress as well as a decrease in mitochondrial respiration. These metabolic profiles also provided evidence that inflammatory macrophages divert metabolites from de novo glycerophospholipid synthesis to inhibit oxidative phosphorylation. In addition, we investigated which metabolic pathways are differentially modulated following primary human monocyte-derived macrophage exposure to Pseudomonas aeruginosa planktonic- and biofilm-conditioned media. Metabolic profiling of PCM- and BCM-exposed macrophages indicated a significant depletion of intracellular glucose without elevation of downstream glycolytic products. These metabolic patterns suggest that PCM- and BCM-exposed macrophages potentially divert glycolytic intermediates towards inositol phosphate metabolism. Overall, our studies provide additional support to previous findings, generate novel results regarding metabolic modulation of human macrophages following activation and exposure to planktonic- vs. biofilm-conditioned media, and contribute new insight to the field of immunometabolism.Item Controlled sprouting in wheat increases quality and consumer acceptibility of whole wheat bread(Montana State University - Bozeman, College of Letters & Science, 2019) Bummer Johnston, Rachel Elizabeth; Chairperson, Graduate Committee: Michael J. Giroux and Carmen Byker (co-chair); John M. Martin, Carmen Byker-Shanks, Sean Finnie and Michael J. Giroux were co-authors of the article, 'Controlled sprouting in wheat increases quality and consumer acceptability of whole wheat bread' submitted to the journal 'Cereal chemistry' which is contained within this thesis.Intentional sprouting of grain to modify grain products nutritional composition and flavor has been in practice for thousands of years. However, few studies have tested the impact of controlled sprouting on wheat flour functionality and flavor. In this study, grain of nine hard red spring (HRS) wheat (Triticum aestivum L) cultivars was sprouted with the goal of attaining a falling number (FN) value of 200 from a starting FN of 350 seconds. Paired samples of sprouted and sound HRS grain were then assayed for nutritional composition, functionality in bread baking, and in bread taste tests. Sprouting reduced grain hardness and test weight while increasing grain color brightness, yellowness, and redness. Whole sprouted grain flour had twice the alpha amylase activity and a large decrease in flour swelling power relative to sound grain flour. Sprouted flour also contained increased free amino acids and monosaccharides while having decreased sugar alcohol content. Total dietary fiber trended down in the sprouted grain flour while starch content remained unchanged. Whole grain flour color parameters were relatively unaltered by sprouting. Sprouting reduced dough mix times while increasing loaf volume. Sensory panel evaluations demonstrated that testers preferred bread prepared from sprouted grain flour to bread prepared from sound grain while also finding that sprouted grain bread tasted less bitter and grainy while also being perceived as sweeter and moister. The results demonstrate that controlled sprouting of wheat grain could be used to increase whole grain flour functionality in bread baking and consumer acceptability of whole grain foods.Item Marine natural products : isolation, identification, and modification of secondary metabolites from Briareum polyanthes, and from Tedania ignis and its associated microorganisms(Montana State University - Bozeman, College of Letters & Science, 1995) Cronan, John Michael