| Popis: |
Microbes are ubiquitous in virtually all habitats on Earth and affect human life in multiple ways, from the health-balancing role of the human microbiome, to the involvement of microbial communities in the global nitrogen and carbon cycles. The capacity of microbes to survive and grow in diverse environments relates directly to their ability to utilize available resources, be they from other microbes or from the environment itself. Hence, understanding how the environment shapes the metabolic functionality of individual microbes and complex communities constitutes an important area of research. In the first part of my thesis work, I explored how environmental nutrient composition and intracellular transcriptional regulation data can be integrated to provide insight into the temporal metabolic behavior of a bacterium through the use of genome-scale stoichiometric modeling approaches (Flux Balance Analysis). Thus I developed the method of Temporal Expression-based Analysis of Metabolism (TEAM), and applied it to Shewanella oneidensis, a bacterium studied for its important bioenergy and bioremediation applications. I found that TEAM improves on previous models' predictions of S. oneidensis metabolic fluxes, and recovers the overflow metabolism that has been seen experimentally. This study demonstrated the value of incorporating environmental context and transcriptional data for the prediction of time-dependent metabolic behavior. In the second part of my work, I extended the exploration of microbial metabolism from single species to complex communities in order to understand the robustness of metabolic functions. Specifically, I implemented novel mathematical analyses of metagenomic sequencing data to ask how functional stability of microbial communities could ensue despite large taxonomic variability. Upon representing in matrix form the metabolic capabilities of all genera found in 202 available metabolic ecosystem datasets, I compared the different communities with each other and with various randomized analogues. My results reveal new connections between the abundance of an organism in the community and the functions that it encodes. Furthermore, I found that genus abundances govern the metabolic robustness of a community more than the distribution of genetically encoded functions among the community members, suggesting that communities rely largely on ecological interactions to regulate their overall functionality. |
