A longstanding major focus of biological oceanography, understanding, predicting, and perhaps manipulating carbon-fixation in the oceans, recently has been of interest to a broader audience of scientists and policymakers. It is clear that the oceanic sinks and sources of CO2 are important terms in the global environmental response to anthropogenic atmospheric inputs of CO2 and that oceanic microorganisms play a key role in this response. However, the relationship between this global phenomenon and the biochemical mechanisms of carbon-fixation in these microorganisms is poorly understood. In this project, we will investigate the carbon-sequestration behavior of Synechococcus Sp., an important abundant marine cyanobacteria for environmental responses to carbon-dioxide levels through experimental and computational methods.

This unique project is a combined experimental and computational effort that emphasizes developing and applying new computational tools and methods. Our experimental effort will provide the biology and data to drive computational efforts and include significant investment to develop new experimental methods for uncovering protein partners, characterize protein complexes, and identify new binding domains. We also will develop and apply new data measurement and statistical methods to analyze microarray experiments.

Computational tools will be essential to our efforts to discover and characterize the function of the molecular machines of Synechococcus. To this end, molecular simulation methods will be coupled with knowledge discovery from diverse biological data sets for high-throughput discovery and characterization of protein-protein complexes. In addition, we will develop a set of novel capabilities for inference of regulatory pathways in microbial genomes across multiple sources of information by integrating computational and experimental technologies. These capabilities will be applied to Synechococcus regulatory pathways to characterize their interaction map and identify component proteins in these pathways. We also will investigate methods to combine experimental and computational results with visualization and natural-language tools to accelerate the discovery of regulatory pathways.

Our ultimate goal is to develop and apply new experimental and computational methods necessary to generate a new level of understanding of how the Synechococcus genome affects carbon-fixation at the global scale. Anticipated experimental and computational methods will provide ever-increasing insight about the individual elements and steps in the carbon-fixation process. However, relating an organism’s genome to its cellular response in the presence of varying environments will require systems biology approaches. Thus, one of our primary goals is to integrate genomic data generated from experiments and lower-level simulations with data from existing literature into a whole cell model. We plan to accomplish this by developing and applying a set of tools for capturing the carbon-fixation behavior of complex of Synechococcus at different resolution levels.

Finally, the explosion of data being produced by high-throughput experiments requires data analysis and models that are more computationally complex, more heterogeneous, and require coupling to ever increasing amounts of experimentally obtained data in varying formats. These challenges are unprecedented in high-performance scientific computing and necessitate developing a companion computational infrastructure to support this effort.