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Fundamental & Computational Sciences Directorate

Biological Systems Science Research Area

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Biological systems science encompasses the ability to measure, predict, design, and ultimately control multi-cellular biological systems and bioinspired solutions for energy, environment, and health. It involves fundamental research and technology development using a systems and synthetic biology approach of natural and engineered biological systems both in the laboratory and in the field.This includes development of technologies focused on how cells, cell communities, and organisms sense and respond to their environment.

Pacific Northwest National Laboratory is recognized internationally for our biological systems science capabilities, including leadership in proteomics and other 'omic technologies, environmental microbiology, systems toxicology, and biotechnology. Our expertise also includes cell biology and biochemistry, radiation biology, computational biology and bioinformatics, bioforensics, and biodetection. Of particular interest are biological dark matter and engineered biosystems. Biological systems science is stewarded by PNNL's Biological Sciences Division but includes staff and research across the Laboratory.

Biological Dark Matter. Scientists can access an ever-increasing number of organisms for which the complete DNA sequence—the genome—is known. While genome sequencing reveals the basic building blocks of life, a genome sequence alone is insufficient for determining biological function. "Unknown genes" are those for which the encoded function is unknown. These genes are part of what scientists refer to as "biological dark matter." PNNL is at the forefront of proteomics and computational research directed toward understanding biological dark matter.

"Biological dark matter is not just the identification of new genes, but the incorporation of the existing and new genes into annotated gene function. Finding the novel genes is only the first step. Determining what the genes do and who they are interacting with are the next steps in linking the discovery of biological dark matter into gene function."
— PNNL scientist Dr. Mary Lipton

Engineered Biosystems. To design engineered biosystems for energy generation, carbon sequestration, or environmental cleanup, we need the ability to look not just at how a cell works, but how it works together in communities. We need to understand how cells work and how the various pieces work together.

The primary challenges in predicting the behavior, manipulating, and engineering microbes and microbial communities are in understanding how microorganisms function and can be altered to enhance the production of desired products. Our approach to is to create sets of integrated technologies that lead to a mechanistic and predictive understanding of biological systems.

Advanced multiscale in situ imaging tools for characterizing structure and function under operating conditions and new multiscale modeling approaches will be used to

  • Create unique microscale environments
  • Integrate 'omics data from microbial communities and their members, interrogate metabolism and kinetics using stable isotope analysis
  • Develop mathematical models to analyze the micro-scale biological processes and predict their macroscale effects.

This will allow us to interrogate, model, manipulate, and engineer metabolic pathways using system-level and synthetic biology approaches in natural and constructed microbial systems.

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