The DOE Genomes to Life (GTL) program is unique in calling for "well-integrated, multidisciplinary (e.g., biology, computer science, mathematics, engineering, informatics, biophysics, and biochemistry) research teams," with strong encouragement to "include—where appropriate—partners from more than one national laboratory and from universities, private research institutions, and companies. "Such guidance is essential for the GTL program to meet its four ambitious goals:

Goal 1: Identify and characterize the molecular machines of life — the multi-protein complexes that execute cellular functions and govern cell form.

Goal 2: Characterize gene regulatory networks.

Goal 3: Characterize the functional repertoire of complex microbial communities in their natural environments at the molecular level.

Goal 4: Develop the computational methods and capabilities to advance understanding of complex biological systems and predict their behavior.

The work described in our project focuses on understanding the carbon-sequestration behavior of Synechococcus Sp. through experimental and computational methods. The major effort of this work is to develop computational methods and capabilities (GTL Goal 4) for application to Synechococcus. Synechococcus is an abundant marine microorganism important to global carbon-fixation and thus the topic of an experimental investigation led by Dr. Brian Palenik and funded by the DOE Office of Biological and Environmental Research Microbial Cell Program (MCP). Dr. Palenik's MCP project is highly complementary to our effort, and he is included in this effort as discussed below.

Ensuring that our project is strategic to the GTL program and that the capabilities developed are broadly applicable to the DOE's life science problems are major goals of this effort. These larger goals cannot only be seen in the discussion of the technical work in this proposal, but also in our project management plan. The guiding philosophy, shared by the project's principle investigators, Heffelfinger and Geist (of Sandia and Oak Ridge, respectively) as well as by the larger team as a whole, of how this work will be carried out is that the effort is a single project, aimed at developing and applying computational capabilities for Synechococcus, with ultimate usefulness for application to the larger DOE life science community. To this end, every effort will be made to ensure that our proposal's five subprojects,

• Experimental elucidation of molecular machines & regulatory networks in Synechococcus SP.
• Computational discovery and functional characterization of Synechococcus SP. Molecular machines
• Computational methods towards the genome-scale characterization of Synechococcus SP. regulatory pathways
• Systems biology models for Synechococcus SP.
• Computational biology work environments and infrastructure

Our effort includes participants from four DOE laboratories (Sandia National Laboratories, Oak Ridge National Laboratory, Lawrence Berkley National Laboratory, and Los Alamos National Laboratory), three universities (U Michigan, UC Santa Barbara, and U Illinois Urbana/Champaign), and four institutes (The National Center for Genomic Resources, Scripps Institution of Oceanography, The Molecular Science Institute, and the Joint Institute for Computational Science). Our approach is highly interdisciplinary because it involves researchers with backgrounds ranging from biology to physics to mathematics. The capabilities to be developed are equally diverse—ranging from new experimental methods to extensions to massively parallel operating systems. It is for these reasons that the ultimate success of this effort will be heavily dependent on our ability to integrate across these dimensions to build and apply capabilities greater than the sum of their parts. More information on this project can be found in our project notebook (password protected).