Carbon Sequestration in Synechococcus: A Computational Biology Approach to Relate the Genome to Ecosystem Response

This talk will provide an update on the progress to date of the Genomics:GTL project led by Sandia National Laboratories: " Carbon Sequestration in Synechococcus sp.: From Molecular Machines to Hierarchical Modeling. " This effort is focused on developing, prototyping, and applying new computational tools and methods to elucidate the biochemical mechanisms of the carbon sequestration of Synechococcus sp., an abundant marine cyanobacteria known to play an important role in the global carbon cycle. While much of our recent progress and results will be presented in detail in the seven or more posters submitted to this meeting (see Davidson et al., Geist et al., Martino et al., Plimpton et al., Samatova et al. Sinclair et al., Xu et al. and others), this talk will recap the larger focus and recent results of the project. Our project's results include experimental data on the Synechococcus carboxysome and CO 2 levels on growth rate and protein expression patterns in Synechococcus (sp. WH8102), the first characterizations of components of the proteome, and characterizations of the phosphorus and nitrogen regulatory pathways in conjunction with computationally derived predictions of these pathways. Our computational tool development efforts relative to processing high throughput experimental data have yielded new methods and algorithms for gene expression array analysis and a radically new tandem MS, MS/MS data analysis method which enables prototype assignment for large and diverse data sets (~60,000 spectra) with a surprising level of confidence. We have also developed and prototyped new computational tools for microbial systems biology, including methods for multi-scale characterization of protein interactions, methods for recognizing protein functional sites, and an integrating framework such tools. In addition to our work with Synechococcus Sp., we have applied these tools to other microbes in collaboration with other Genomics:GTL projects including the ORNL-PNNL microbial proteomics effort for Rhodopseudomonas palustris (with F. Larimer and H. McDonald). Our efforts to develop and apply modeling and simulation tools have yielded structural insight into the specificity of the carbon fixing enzyme RuBisCO as well as a computational capability to track spatial and temporal variations in protein species concentrations in realistic cellular geometries for important cyanobacterial subcellular processes. Finally, we have constructed an integrated data infrastructure which allows advanced search and queries across a large, diverse set of data sources (e.g. databases of sequence, structure, pathway, protein interaction, and raw mass spectra and microarray data). Our " Synechococcus Encyclopedia, " contains all currently available …