Theses and Dissertations at Montana State University (MSU)
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Item Emergence of cooperative behavior in microbial consortia(Montana State University - Bozeman, College of Letters & Science, 2018) Schepens, Diana Ruth; Chairperson, Graduate Committee: Tomas GedeonCooperative microbial communities and their impact are ubiquitous in nature. The complexities of the cross-feeding interactions within such communities invite the application of mathematical models as a tool which can be used to investigate key influences in the emergence of cooperative behavior and increased productivity of the community. In this work, we develop and investigate a differential equation model of competition within a chemostat between four microbial strains utilizing a substrate to produce two necessary metabolites. The population of our chemostat includes a wild type strain that generalizes in producing both metabolites, two cross-feeding cooperator strains that each specialize in producing one of the two metabolites, and a cheater strain that produces neither metabolite. Using numerical methods we consider three key characteristics of the microorganisms and investigate the impact on the emergence of mutual cross-feeding in the community. First, we investigate the impact that substrate input concentration and the rate and type (active vs. passive) of metabolite transport between cells has on the emergence of cooperation and multi-stabilities resulting from the competition. Second, we investigate the role that resource allocation within metabolic pathways plays in the results of the competition between cells with different metabolite production strategies. Introducing metabolite production cost into the model leads to new outcomes of the competition, including stable coexistence between different strains. Lastly, we examine the effect that an initial population of a non-cooperative cheater strain has on the outcome of competition. Our results show that the emergence of a cross-feeding consortia relies on the availability and efficient use of resources, ease of transport of metabolites between cells, and limited existence of cheaters.Item New methods in computation of reaction fluxes from metabolomics data(Montana State University - Bozeman, College of Engineering, 2018) Salinas Duron, Daniel; Chairperson, Graduate Committee: Brendan MumeyChanges in cellular metabolism can be deduced from how they affect the measurable metabolites in cell samples. We provide methods to compute metabolic reaction rates from changes in measurable metabolites over time. The methods provided are intended to overcome technical challenges, such as the inapplicability of a steady state assumption, heterogeneity of samples from different donors, and the lack of targeted metabolomics data. Solutions to these challenges involve identifying metabolites constrained even under non-steady state, using components analysis to find the donor consensus, and using an integer linear program to solve a set cover variant designed to generate targeted data from untargeted data. The methods are applied on data derived from diseased articular cells. The results show that the reaction rates inferred from the incomplete data are biologically relevant, and that the minimal pathways captured ancillary processes that alternative approaches ignored. We conclude that, although the resulting rates and pathways are not conclusive, they provide useful guidance on experiments to pursue. On the experimental side, our findings have lead us to believe that osteoarthritic chondrocytes respond to compression by initiating protein synthesis, opening the possibility of physical therapy as a stimulus for cartilage regeneration.Item Novel nitrogenous heterocycles from the tunicate Clavelina picta(Montana State University - Bozeman, College of Letters & Science, 1990) Raub, Michael FranklinItem Secondary metabolites from the Bermudian sponge Tedania ignis(Montana State University - Bozeman, College of Letters & Science, 1990) Dillman, Rhonda LynnItem Diterpenes and other secondary metabolites from Ptilosarcus gurneyi, Briareum polyanthes and Igernella notabilis(Montana State University - Bozeman, College of Letters & Science, 1990) Hendrickson, Robert LoranItem Purification and characterization of Pseudomycin, a phytotoxin and antimycotic produced by Pseudomonas syringae(Montana State University - Bozeman, College of Agriculture, 1990) Harrison, Leslie AnnItem Investigation of biologically active metabolites from symbiotic microorganisms(Montana State University - Bozeman, College of Letters & Science, 1988) Stierle, Andrea Anne