The Department of Energy (DOE) recently published a guide called the Genomics:GTL Roadmap: Systems Biology for Energy and Environment which outlines the science and technology infrastructure requirements for the next wave of the genome revolution. The roadmap, the result of dozens of workshops and the participation of hundreds of scientists, is aimed at accelerating systems biology research, especially in the area of bio-energy, with the objective of reducing U.S. dependence on fossil fuels by developing viable renewable energy sources. The roadmap details the equipment, research, computational needs, and facilities required to support the DOE's clean energy, carbon management, and environmental clean-up missions in the coming decades.
“The Genomics:GTL Roadmap is a comprehensive resource for systems biology. It covers the sciences involved, the instrumentation, how they might be integrated into facilities, and how they are all going to be used. It is a great source document,” says Michael Knotek, Ph.D., of Knotek Consulting, who has shaped research initiatives at seven of the DOE’s nine national laboratories and contributed to the roadmap.
The Genomics:GTL program supports advanced research in systems biology aimed at harnessing the microbial world to produce clean energy, absorb carbon dioxide in the atmosphere, and mitigate radioactive contamination in the environment. Microbes—organisms that are too small to be visible to the naked eye—are found in virtually every habitat in nature, even harsh environments such as deserts, the deep sea, and the arctic poles.
“Microbes have co-evolved with the earth for four billion years and have learned how to deal with many of the chemical and energy problems that we are now befuddled with. We need to learn how they function at the genomic level, and how to optimize those functions to solve some of these problems,” says Knotek.
The genome of an organism is essentially the hereditary information of an organism encoded in the DNA. Genomes dictate the functionality of living systems at every scale by creating the proteins and mechanisms that create cells and complex systems.
“A genetic analysis of microbes was conducted on a barrel of seawater from the Sargasso sea, which was thought to be a dead sea and hence biologically simple, and they found 50 times more genes in that barrel of water than the human genome contains. In that sense, microbes have a genetic diversity that dwarfs every other living thing on the planet. We know about some of these, but we need to understand hundreds more,” says Knotek.
Deconstructing and re-engineering the genetic properties of an organism requires sophisticated equipment coupled with considerable amounts of data storage and computer modeling. As a result, the technological demands of system-based research are unprecedented.
“You have to be able to look at every sample under every condition to really understand an organism’s overall process. Proteins, machines, and microbes don’t function in isolation; they are dramatically integrated into their environments. We have to study phenomenology at every scale from individual organism to ecosystem,” says Knotek.
Keys to the Machine
Intensive computing and technology infrastructure are essential for the rapid development of biotechnological solutions. The new era of systems biology depends on technology as much as it does on research procedures. Gathering, managing, analyzing, and modeling all the data necessary is a profound challenge.
“Any facility built now must have massive data capabilities. Biologists are finally realizing that data management may be the dominant issue in their world today,” says Knotek.
Biology facilities of the future will feature high-throughput robotics for testing thousands of samples, combined with extensive data infrastructure to capture and organize the data. Advanced computer modeling will provide researchers with functional tools for deciphering the data and engineering the proteomic functions of microbes.
The next wave of facilities will also contain mass spectrometry; optical, neutron, and electron microscopy; vibration stabilization; sophisticated bioinformatics tools; and powerful computer work stations with modeling capabilities linked to massive databases.
The roadmap calls for the creation of a vast integrated computational environment and shared knowledge base with DNA sequence code as its foundation. The system will assimilate a vast amount of genetic data as it is produced and offer scientists across the country access to an array of powerful resources including archives of large-scale mass spectrometer data, molecular modeling, and sophisticated analytical tools.
Biomass into Biofuel
A major focus of the roadmap is using systems biology to study how high-yield biomass crops—such as switchgrass, miscanthus, and poplar trees—can be more efficiently converted into biofuels.
“The country has access to roughly a billion tons of biomass if we can figure out how to convert it. This could account for 30 percent of our oil, or 50 percent of our imports. We’re also looking at the fact that less than 100 million acres of energy crops could, under the right conditions, eliminate all of our oil dependency,” says Knotek.
Biomass (which is essentially any plant-derived substance) is comprised of three main compounds: cellulose, hemicellulose, and lignin. During conversion, plant cellulose is broken down into sugars that are fermented by bacteria or yeast into biofuels like ethanol.
Development of biofuel is a big deal because it combines the energy, agriculture, and biotechnology sectors. Also, since carbon from biofuels was recently extracted from the environment by plants, burning it does not result in a net increase of atmospheric CO2.
“There are numerous options for finding more oil and energy, but if we are worried about reducing carbon in the atmosphere, biofuels are kind of the only hope for the next 30 to 50 years, and they have great economic benefits,” says Knotek.
The DOE recently held a “Biomass to Biofuels” workshop to facilitate the development of these technologies. The workshop looked at three general areas in relation to systems biology: optimizing growth of energy crops; learning how to break cellulose down to sugars; and fermenting the sugars into alcohol for use as fuel. Currently, this process requires large processing plants and complicated work with concentrated acids to break down the cellulose. The goal is to use genomic research to consolidate these processes into microbes so that they occur rapidly at the cellular level, are more energy efficient, and are cleaner.
“To study microbial communities, we need to cultivate these organisms in complicated chemostats and then analyze all their component pieces in a comprehensive way so we can discover what proteins are involved, and what processes are going on,” says Knotek.
Achieving these goals will require a technological infrastructure that does not currently exist. The roadmap originally called for the creation of four user facilities, each with a different focus (protein production, molecular imaging, proteome analysis, and systems biology). The DOE’s energy mission has increased in priority since the original plan was formulated. As a result, the Office of Science has decided to build one or two vertically integrated bioenergy research centers that will have all of these capabilities in one place, and will help accomplish the objectives more rapidly and at reduced cost.
New Systems, New Approaches
In addition to revolutionizing the way labs are designed and built, systems biology has significant implications for private industry and academic teaching programs. Research institutions will need to adapt to using increasingly sophisticated tools and techniques in order to keep pace with rapidly changing scientific development.
“It’s very hard for biologists to adapt to the concept of pooling data and developing computerized modeling tools to achieve a higher level of science, but if they’re going to do systems biology they will have to leverage all of their data and tools,” says Knotek.
Academic institutions will also need to provide more training, facility infrastructure, and educational support for computer modeling, advanced imaging, and micro technologies.
“A lot of new labs will be focused on things like micro-fluidics and nanotechnology.
We are going to see more cross-disciplinary facilities as research organizations and educational institutions bring together multiple fields to solve specific problems,” says Knotek.
By Johnathon Allen