On the path from sequence to function and beyond.
A major strategic target for the next decade is increasing automation and streamlining of all steps in single-cell genomics pipelines, with the goal to be able to handle tens of thousands to millions of single cells in a day, adapt the pipelines to different sample types (including plant tissues and single eukaryotic chromosomes) and expand them to complementary systems-level approaches including preparation of single cells for metabolic or proteomic studies. The DOE JGI is well positioned to accomplish these goals with infrastructure and expertise in single-cell handling and molecular methods dealing with extremely small template amounts. Investments are expected in miniaturization of sample handling to move beyond micro-titer plates and into higher throughput workflows, as well as in the implementation of targeted single cell approaches. By being able to isolate single cells, nuclei or chromosomes of interest on a production-scale, we expect to be able to reduce the complexity of metagenome samples to aid in simplifying analytic methodologies and to obtain microorganisms that are biologically important, but difficult to obtain. This coupling of high-throughput single cell capabilities with transcriptomics, proteomics and metabolomics is expected to yield substantially improved insights and comprehensive systems biology level views of our environment.
Our emerging capability in metabolomics research will focused on developing a comprehensive understanding of metabolic processes, particularly physiological ‘state changes’ that occur as a result of environmental perturbations. A major challenge has been the lack of tools to resolve these processes both in terms of network topology and spatial localization. Hence, we have made major progress pioneering methods for gas phase ion generation and applying mass spectrometry for studying metabolites in complex biological systems. Central to these efforts are the development of experimental and computational approaches to study these processes in space and time using activity profiling, stable isotope tracing, and mass spectrometry imaging.
We are interested in dynamic metabolic responses of cells to environmental perturbations ranging from shifts in nutrient availability to environmental stresses. Central to these efforts are the development of experimental and computational approaches to study these processes using mass spectrometry based metabolite and activity profiling, stable isotope tracing, and mass spectrometry imaging. Together these allow us to comprehensively characterize metabolic activities, dynamics and localization within complex cellular systems to predict responses and design interventions.