To promote development of a new generation of characterization technologies,the U.S. Department of Energy's (DOE) Office of Science Office of Biological and Environmental Research (BER) hosted the New Frontiers in Characterizing Biological Systems workshop in May 2009. Experts from scientific disciplines relevant to DOE missions and from the enabling technologies (e.g., optical spectroscopy, genomic sequencing technology, electrochemistry, electron microscopy, and mass spectrometry) met to determine the opportunities and requirements for identifying and developing new tools and analytical approaches for characterizing cellular- and multicellularlevel functions and processes that are essential to develop solutions for DOE missions in biofuels, carbon cycling and biogeochemistry, low dose radiation, and environmental stewardship. The intent of the workshop was to broadly explore future technology capabilities that are needed, not current technologies and their development.
Publication date: December 2009
Suggested citation for this report: U.S. DOE. 2009. New Frontiers in Characterizing Biological systems: Report from the May 2009 Workshop, DOE/SC-0121, U.S. Department of Energy Office of Science (http://genomicscience.energy.gov/characterization/).
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Understanding the relationship between the genome and functional processes is the most significant challenge and potentially enabling advancement that faces modern biology. Elucidating this connection presents opportunities for realizing sustainable energy solutions and responsible management of natural resources. Understanding the function of the genome is at the core of the Department of Energy’s (DOE) Genomic Science program and is central to realizing DOE’s mission goals in bioenergy research, carbon management, and environmental stewardship. Just as genomic science is central to these mission goals, technology advancements are central to genomic science and to unlocking the connections between the genome and functional processes occurring at cellular to global environmental scales. New developments in characterization technologies will be essential for driving advances in genomic science and in our understanding of the genomic bases of natural processes.
In May 2009, DOE’s Office of Biological and Environmental Research (BER) held the New Frontiers in Characterizing Biological Systems workshop to address the next generation of challenges in genomic science and its connection to functional systems. The workshop included a diverse array of scientists and engineers with expertise in the mission-relevant biological and environmental sciences and in the analytical and physical sciences. Working groups were focused on defining the challenges associated with studies at the cellular, multicellular, and interfacial levels. Common themes and priorities emerged from the different groups. There was universal agreement that appropriate advances in characterization technologies will first depend on articulation of the major challenges that face the biological and environmental science communities. To that end, this report— rather than comprehensively discussing currently available technologies—highlights the major challenges and outlines the future technological capabilities required to meet them. Workshop participants identified numerous knowledge gaps that inhibit the understanding of biological systems, and these can be distilled into three major challenges:
These primary knowledge gaps are relevant to understanding the processing of biomass into different chemical forms, the cycling of carbon, and the transformation of contaminants in the environment. They are fundamental challenges intrinsic to diverse biological and environmental concerns. Timely resolution of these problems will revolutionize our understanding of biological systems and significantly advance DOE mission science. Achieving these goals will depend on a transformation of current measurement capabilities. Numerous technological approaches can be considered.
Regardless of approach, the specific technical capabilities needed to fill these knowledge gaps include:
Overcoming these technical challenges will facilitate basic understanding of biological processes, not just at a particular physical or temporal scale, but the linking and relating of such scales to genomic information. Focused advancements in characterization technologies will address critical knowledge gaps and support the realization of mission needs. These advancements will broadly impact the biological and environmental sciences in general and ultimately transform biology into a quantitative science.
Moving forward in these needed developments will require concerted efforts on several fronts. Key among these is investment in stimulating technology developments. These developments will need to proceed within the context of the primary biological challenges identified in this report. A priority should be the development of approaches for simultaneously assessing multiple species at appropriate spatial and temporal resolution. This likely will proceed through combinations of different measurement techniques. Technology advancements also must commence with developing high-throughput parallel approaches for making sensitive measurements in heterogeneous environments. Small molecules within single cells and small populations must be tracked. Measurement techniques alone will not be sufficient. Rather, what is required to reveal function is the ability to manipulate relevant biological, chemical, and physical variables while tracking their effects on biological systems.
A second key focus should be on promoting analysis of the biological systems most relevant to DOE missions. We must move past the study of relatively simple model organisms and toward the study of organisms within their natural environmental setting (e.g., in planta and in terra). Initially, organism systems that are representative of the technological and environmental problems we wish to understand must be identified. Capabilities for culturing or studying organisms at the single-cell level need to improve along with the tools for manipulating and studying these organisms at the molecular level. Systems research will need to progress past the study of individual organisms in isolation and toward systems of increasing biological complexity, replete with the structuring and heterogeneity found in natural systems. Interrogating natural systems in situ should be a long-term goal.
A third focus should be on integrating biological and technological developments through computational tools. Large, disparate datasets must be combined and analyzed to yield new insights into the function of biological systems across diverse scales. Iterative cycles of experimentation and modeling in concert with new theory will be needed to define the appropriate scales for measuring, modeling, and functionally understanding biological processes. This integration will need to capitalize on DOE BER traditions and success in integrating scientific disciplines and in solving grand challenge problems. Multidisciplinary teaming should be promoted and facilitated through integrative training opportunities, incentives for collaborative science, and facilitated access to high-end technologies.
Understanding the connections that link the genome to events at different scales promises to unravel many of the challenges facing the biological and environmental sciences. Such insight will enable effective routes to sustainable energy solutions and responsible stewardship of the environment. Analytical technology developments are key to sustaining progress toward these goals and addressing the challenges and knowledge gaps that emerge. The complexity, emergent properties, and multiple scales of biological systems present substantial obstacles. The tremendous progress in characterizing whole genomes, which only a few decades ago was considered a nearly intractable problem, was enabled by the focused integration of a biological problem with technological advances in analytical measurements and computation. Similarly, the seemingly daunting challenges that we now face can be addressed through focused developments and bold advances in characterization technologies.
*Note to readers: The following notice applies to the figure: "Expression of Lactose Permease in E. coli" p. 27, which is used with permission from Science and AAAS for the report New Frontiers in Characterizing Biological Systems.