"Significant improvements in research techniques are occurring at an exponential rate, with quantum changes happening every year, so organizations can't just do more of what they're doing now and expect to keep up," says Michael L. Knotek, Ph.D., of Knotek Consulting, who has shaped research initiatives at five of the U.S. Department of Energy's nine national laboratories. "How science is practiced, the skills needed, and the technical demands will change rapidly—in time frames shorter than a traditional research project."

Revolutionary improvements in biology and nanotechnology are demanding new approaches to the design of research facilities. One of the most significant factors is the increasing need for powerful computer clusters to store data, conduct modeling, visualize results, and develop new concepts, transforming the research cycle.

"Investigators developing technology in industry no longer go through costly and laborious prototyping and pilot programs. Everything is designed and modeled on computers first. Entire steps in the development process are being discarded as scientists go straight from research to full-scale production," says Knotek.

As a result, modern labs need immense amounts of data storage with advanced database and bioinformatics capabilities. According to Knotek, researchers will increasingly depend on secure high-speed networks that connect labs with databases and other facilities around the globe.

Tomorrow's labs will also need to accommodate large multidisciplinary teams consisting of investigators from different scientific backgrounds, and incorporate increasingly large high performance instruments and robotic production equipment.

"Biology, nanoscience, materials science, device synthesis, computational chemistry, physics, and analytical techniques have all gone through similar revolutions and are now coming together. Any new cutting-edge facility must be able to support the integration of key technologies from many of these disciplines," says Knotek.

Solving Tomorrow's Problems Today

Building on the successes of the Human Genome Project, the U.S. Department of Energy (DOE) has initiated a program called Genomics:GTL (GTL) (formerly Genomes to Life), aimed at achieving a comprehensive, systems-based understanding of life. The billion dollar enterprise will go beyond analyzing individual components, such as genes and DNA sequences, to developing an integrated view of life at the whole-systems level.

Scientists now possess the DNA sequences of genomes for many organisms, from microbes to plants to humans. The GTL program will leverage that data, along with newly developed high-throughput technologies, to solve important global problems.

According to the DOE, one of the biggest challenges facing humanity in the next century is climate change. Humans generate approximately six billion tons of carbon a year from energy production alone. Based on population growth and standard of living estimates, that figure is expected to grow between a factor of four and ten over the next century.

"In order to reach an acceptable level of CO₂ in the atmosphere by the end of the century, we have to deal with between 1,000 and 2,500 gigatons of carbon. We must either capture it and sequester it, or not produce it in the first place," says Knotek.

Scientists are looking at how ocean and terrestrial microbial systems, which cycle approximately 150 gigatons of carbon dioxide annually, can be harnessed to help solve these issues. Microbial processes are being analyzed as sources of bio-fuels to power the transportation sector, and researchers are studying large-scale energy crops that could be used to turn cellulose into bio-fuels such as ethanol or bio-diesel. Because cellulose is formed during photosynthesis, as plants absorb sunlight and carbon dioxide, biomass fuels are carbon neutral. Advanced technologies have the potential to create a carbon negative energy cycle through biomass processing to hydrogen and carbon which is subsequently sequestered.

"Detailed knowledge of microbes, and the complex interaction of molecular machines within these cellular communities, would have profound implications for understanding these vast natural systems and energy producing processes. These technologies could be worth ten trillion dollars over the coming century alone," says Knotek.

To achieve the comprehensive understanding of life required to make these technologies feasible, large-scale research facilities will be needed to study the thousands of components that are interacting at any given moment in a cell. Networked clusters of supercomputers will be required to process this information and model full-scale life systems interacting from molecular time scales to geologic time.

"Systems biology has totally changed how biological research is practiced. Now we're seeing large strategic teams working with high-throughput automation systems doing research at a whole new level," says Knotek.

As part of the GTL project, the DOE is planning to develop four bioscience facilities that will serve as national research venues for multidisciplinary systems biology. The first of these facilities will feature automated high-volume production of the proteins and molecular tags needed to do biology research on a genome-wide scale.

According to Knotek, The Protein Facility will look more like a semiconductor fabrication line than a biology lab, with hundreds of large robots manufacturing highly purified, meticulously folded proteins at a rate of tens of thousands per year. The facility will also develop genomic databases and computational tools accessible to the greater scientific community.

The GTL Machines facility will focus on the characterization and imaging of molecular machines. It will feature rows of huge electron microscopes aimed at studying the function of molecular machines.

The Proteome Facility will focus on whole proteome and molecular profile analyses. Researchers will analyze gene expression, proteomes and metabolites in individual cells and community systems under controlled conditions using numerous bioreactors.

The Cellular Systems Facility will be designed as a user-oriented laboratory with the infrastructure and expertise to allow scientists to probe the function of microbial communities.

"More than the other three facilities, The Cellular Systems Facility will have to overcome major challenges in terms of currently available technologies for measuring the dynamic states of living cells," says Knotek.

As a result, it will rely heavily on phased R&D and pilot projects to develop new technologies and instrumentation by the time it comes on-line in 2010.

Systems and Networks

Knotek emphasizes that these new facilities will require tremendous computing power, combined with increasingly large spectrometry, imaging, and robotic equipment.

The Fourier Transform Ion Cyclotron Mass Spectrometer located in the DOE's Environmental Molecular Sciences Laboratory, on the campus of Pacific Northwest National Laboratory, weighs 65 tons, has a resolving power of a billion, and can do the proteome of a microbe in one hour. The planned GTL protein characterization facility will house dozens of these types of tools, each generating petabytes of multivariate data a month.

Dealing with all that raw data is a big challenge. It's an inconceivable amount of information. If you tried to conduct an experiment analyzing the behavior of all the proteins in a cell the old way, it would take hundreds of grad students forever. Today, we can do it in an hour, but you can't do these experiments without massive computers and very cleverly designed data architectures and tools," says Knotek.

Another major challenge facing tomorrow's lab designers is the paradox of high-powered imaging. In order to analyze smaller and smaller phenomena, researchers need larger and larger tools, which must be isolated from pumps, human traffic, and environmental disturbances.

In many university facilities the imaging tools are located in the basement because it is the only place stable enough. New labs must be able to put these tools anywhere, which means that they will have to be seismically, electrically, and thermally isolated," says Knotek.

The convergence of systems biology, nanotechnology, computational analysis, materials fabrication, and robotics have moved science research into a new technology-intensive era. As tools and methodologies change, facility designers will be pressed to make sure researchers are able to keep pace with rapidly evolving technologies.

There are a lot of good opportunities right now because organizations can make savvy investments and take a leadership position very rapidly, but the situation also increases the possibility of making costly mistakes. Huge areas of science will be left behind because they can't keep up with the technological advancements," says Knotek.

By Johnathon Allen

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