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Biomolecular Systems Initiative

Steve Wiley, Director

The focus of biological research is undergoing a fundamental shift from a descriptive to a more quantitative and predictive approach to answering biological questions. This transition is the result of advances in genome sequencing, the ability to acquire massive amounts of data, the expansion of computational resources, and the introduction of powerful new analytical technologies. Pacific Northwest National Laboratory's (PNNL's) Biomolecular Systems Initiative (BSI) is aligning the lab with this transition. Through the BSI we are:

  • positioning PNNL to be a national leader in the emerging field of systems biology through the advancement of intellectual concepts and the development of technical infrastructure
  • using our leadership role to influence programs of national significance such as DOE's Genomes to Life (GTL) program and the National Institutes of Health (NIH) Roadmap Initiatives
  • building the scientific teams and organization necessary to make biology a cornerstone of PNNL's “systems science” and to provide the intellectual leadership for the design of new biological facilities and infrastructure capable of accommodating these multidisciplinary teams
  • advancing our high-resolution, high-throughput technologies by exploiting PNNL's strengths in instrument development and automation and applying these technologies to solve large-scale biological problems.

We have strengthened and expanded the biological science infrastructure at PNNL to be competitive and to secure funding from national science programs to aid in further growth of this research area. Our multidisciplinary teams of scientists are very active in pursuing and obtaining funding from the U.S. Department of Energy (DOE), National Institutes of Health (NIH), Department of Homeland Security (DHS), National Aeronautics and Space Administration (NASA), Office of Navel Research (ONR), and the U.S. Environmental Protection Agency (EPA).

Our major accomplishments to date include building the teams necessary to integrate scientific disciplines to collectively work together toward solving large-scale biological problems. We have established scientific collaborations with leading institutions around the nation that have resulted in programmatic funding and publications in peer-reviewed journals. Through invited talks and presentations at national and international conferences, we have raised awareness of the BSI and of PNNL's biological capabilities. We are building a comprehensive computational infrastructure that includes software for bioinformatics, modeling, and information management. To be more competitive in obtaining programmatic funding, we will continue to invest in new capabilities and technologies such as cell fractionation, affinity reagents, high-speed imaging, affinity pull downs, and ultra-fast proteomics. This will help us build world-class expertise in the generation and analysis of large, heterogeneous sets of biological data. The ability to productively handle extremely large and complex datasets is a distinguishing feature of the biology program at PNNL.

Proteins with fluorophores under the microscope.
Researchers at Pacific Northwest National Laboratory label proteins with fluorophores to study their motion under the microscope. The dynamic movement of proteins creates an extremely complex motion picture. PNNL's Biomolecular Systems Initiative is developing the quantitative tools necessary to study protein behavior. Click for a larger version.

The BSI Supports Four Scientific Areas

  • Interrogative Cell Signaling – A systems approach is being used to understand the role of regulated ligand shedding in the ability of cells to detect their immediate microenvironment, referred to as context detection. The role of regulated protein shedding in cell communication appears to be a fundamental, evolutionarily ancient mechanism involved in tissue remodeling, embryogenesis, stress responses, and tissue homeostasis. Disruptions in this signaling system appear to be associated with many types of cancer.
  • Interrogation of Microbial Biofilm Activity and Behavior – A better understanding is being gained about biofilms, which are complex communities of microorganisms that adhere to surfaces. Biofilms allow bacteria to persist in many different types of environments; protect bacteria embedded within them, making these bacteria remarkably difficult to treat with antimicrobials and highly resistant to the mammalian body's defense mechanisms; and have industrial applications such as processing sewage and treating petroleum-contaminated groundwater.
  • Spatial and Temporal Proteomics – We are working to understand how self-organizing signaling networks integrate competing environmental stimuli to promote a range of different cellular responses that underlie adaptive and pathological behavior.
  • Bioanalytics – Capabilities are being developed to detect, quantify, and model the presence of biologically significant molecules. These capabilities are important tools for studying biological function. They also have a wide variety of applications beyond basic biology, including the assessment of microbial health at bioremediation sites, detection of pathogenic microbes released as biothreats, and development of clinical assays for biomarkers that indicate infection or disease.

Systems Biology at PNNL

Research & Capabilities

Resources

BSI Scientific Areas

Biomolecular Systems Initiative, image