The goal of the LBNL Genomic Science Program Science Focus Area (SFA), also referred to as ENIGMA (Ecosystems and Networks Integrated with Genes and Molecular Assemblies) is to understand the mechanisms driving the subcellular, cellular, and intercellular networks of microbes that in turn drive macroscopic biogeochemical processes, extending this understanding to the larger framework of microbial communities and ecosystems relevant to DOE missions. To this end, the SFA develops and applies novel platforms for high resolution/high throughput metagenomics, genetics, transcriptomics, proteomics, metabolomics and structural biology approaches to examine the systems biology underlying microbial ecosystems and rapidly advance environmental microbes performing key processes of interest to model-organism status. Guided by studies of microbial consortia and in situ environmental research, single-organism molecular data will be extended across increasingly complex microbial communities to determine the means by which these networks transform environmental signals to behaviors and to link laboratory results to the measurements from field studies. The SFA enables multi-scale studies through the development of a sophisticated computational framework for storage, analysis, visualization and modeling of these data. The ultimate goal of the SFA is to develop new frameworks for collecting and quantitatively analyzing multi-scale information—from molecules to organisms, from cells to communities, and from communities to ecosystems.