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Multiscale, multiparadigm metabolic modeling of the keystone diazotrophic cyanobacterium, Trichodesmium erythraeum
Gardner, Joseph Jay
Gardner, Joseph Jay
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2019
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2020-09-24
Abstract
Earth is a crowded place; studies estimate between 2 and 12 million species exist on earth, with new organisms being formally described every day. This biodiversity is a result of organisms being forced to cohabitate in innately competitive environments; proximity and nutrient limitation require organisms to interact. Current modeling techniques neglect many of these phenomena, considering cells as separate entities, homogeneous populations, or static members of a population. Biological data conflict with these models: organisms are highly dynamic even in the most ideal growth scenarios. Moreover, they operate multilaterally, optimizing many responses to their environments, needs, and other cells, reflecting multiobjective biological strategies for which there is no current elegant mathematical explanation. Expanding these computational techniques to better capture biology will help reduce the solution space of experimentation, widen research focuses, characterize existing ecosystems, and apply better predictions. This work addresses some of the fundamental shortcomings of current metabolic modeling techniques while characterizing a crucial diazotrophic cyanobacterium, Trichodesmium erythraeum. It uses genome-scale modeling approaches to characterize a unique metabolism at the center of the carbon, nitrogen, and phosphorus biogeochemical cycles. It ties these models to experimentation, both personally conducted and from literature, anchoring the findings to biological reality and determining the needs of the field. It progresses to generate a MultIscale MultiObjective Systems Analysis (MIMOSA) framework that allows cells to self-govern within the context of a community and environment, creating emergent cell behavior and better illustrating the dynamic procedures of individual cells. Finally, it employs these models to interrogate the unique nitrogen fixation capabilities of T. erythraeum, presenting hypotheses on its productivity as it integrates carbon fixation, a circadian cycle, and microaerobia to operate efficiently. The work is a step toward distilling actionable information from a plethora of resources in a significant microorganism.
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