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Editorial: Unraveling Complex Biological Systems

Frank Harris
Frank Harris

A new age of biology is being ushered in with the sequencing of the human and other genomes. Armed with this information about the order of DNA bases in genes and the chromosomes on which they sit, scientists can now initiate the steps required to understand processes that occur in the human body, down to the level of the molecule. This new information promises a rich harvest: drugs targeted to our own personal DNA, early warnings of diseases to which we are genetically predisposed, and a more profound understanding of human evolution.

Now that we know where different genes are located on the 23 pairs of human chromosomes, scientists have begun to focus on what these genes do. Which genes are silent in each organ? Which genes are turned on, or expressed, directing cells to produce proteins in specific shapes that determine their functions? What are the exact structures of specific proteins that cause the body to become ill or work well? Can drugs be made to dock with these proteins, like two jigsaw-puzzle pieces fitted together, to block or enhance their action in the body, improving overall health?

In this postgenomic era of biology, scientists are learning about gene expression and the nature of the expressed proteins—understanding life's processes at the molecular level. Such knowledge could lead to therapeutic drugs targeted to each individual's genome, ensuring their effectiveness.

Barry Berven and Dabney Johnson inspect the hoods in the new biology lab at ORNL
Barry Berven and Dabney Johnson inspect the hoods in the new biology laboratory at ORNL. (Photo by Curis Boles.)

Researchers at ORNL—where the function of messenger RNA, the chromosomal basis for sex determination in mammals, DNA repair processes, and several important mouse genes have been discovered-are taking an interdisciplinary approach to unraveling complex biological systems. This approach also integrates studies of mouse mutations with studies of genes and proteins, using various technologies—automated DNA sequencing, biomedical imaging, microarrays (gene chips), mass spectrometry, neutron sources, and terascale supercomputers.

As described in this issue of the Review, we are determining which genes are expressed in microbes, fish, and mice during exposures to environmental toxins. We are searching for unique protein signatures of various microbes. We have already computationally analyzed the human and mouse genomes, to predict the structure of genes and proteins and make educated guesses about protein function. We have one of the world's top-ranking groups in the area of computational prediction of protein structure. We have identified mouse genes that play a strong role in genetic diseases similar to maladies that afflict humans, such as cancer, obesity, and epilepsy. We are collaborating with researchers in the Tennessee Mouse Genome Consortium to determine which of ORNL's 60,000 mutant mice are excellent models of human genetic diseases that can be used to test the effectiveness of various therapies.

Our experimental research is focused on a variety of organisms: microbes, zebrafish, hybrid poplar trees, and mice. Our computational research is focused on microbial, mouse, and human genes and proteins. We are now taking advantage of ORNL's leading mass spectrometry capabilities to study proteins expressed by these organisms under varying conditions. The success of much of this work has depended—and will continue to depend—on the strength of the collaborations involving scientists at ORNL and elsewhere who represent many different disciplines.

ORNL's goal is to be a center of excellence and a resource for our understanding of (1) complex biological systems, from the molecular to the cellular and to the organismal level, with emphasis on human susceptibility to becoming ill from exposure to low levels of radiation and other environmental agents, and (2) the interactions of organisms with the environment. Innovative ways to observe and understand the functioning of complex biological systems will be developed and applied through expanded partnerships, to meet the needs of the U.S. Department of Energy.

One proposed DOE program is the "Genomes to Life" initiative. Its goals include identifying "protein machines," the multiprotein complexes that carry out the functions of living systems; characterizing functions of microbes in their natural environments; and developing computer modeling technologies to determine how complex biological systems can serve DOE's environmental and health missions. ORNL hopes to shed light on these complicated processes through its systems biology expertise and resources, including DOE's new Center for Structural and Molecular Biology (which will take advantage of the combined expertise of resident and visiting researchers in mass spectrometry, computational biology, and neutron sciences) and DOE's Center for Computational Sciences.

This special issue of the ORNL Review showcases ORNL's achievements and capabilities not only in understanding genes and proteins but also in bioengineering developments that could improve health care, such as the lab on a chip, cantilever devices, and the multifunctional biochip. We also have pioneered a way to cure cancer in mice that may have applications to humans. These areas of endeavor are likely to be hallmarks of science and technology in this century.

Harris signature

, Associate Laboratory Director for Biological and Environmental Sciences

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