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August 2013
P2EP: The Dynamics of New Biology
By Pete Prunkl

     Under the header of “Not Your Father’s Biology,” the National Research Council (NRC) issued a report entitled A New Biology for the 21st Century. In it, the writers coined the term “New Biology” to describe the dynamic needed for the life sciences to address some of our nation’s most pressing problems—in loss of ecosystem services, alternatives to fossil fuels, and individualized health care.

     The writers see this New Biology initiative as a sea change: “Biological research is in the midst of a revolutionary change due to the integration of powerful technologies along with new concepts and methods derived from inclusion of physical sciences, mathematics, computational sciences, and engineering. As never before, advances in biological sciences hold tremendous promise for surmounting many of the major challenges confronting the United States and the world.”

     The NRC report advocates addressing our nation’s most pressing problems in the areas of food, climate, energy and health—sectors that in their larger aspects represent 50 percent of the U.S. economy. It makes clear the need for biologists to reach across the hierarchy of science allying themselves with physicists, chemists, computer scientists, engineers and mathematicians in multi-disciplinary teams to solve the most urgent multi-disciplinary problems.

     The NRC anticipates that lines between disciplines will be blurred; physicists and mathematicians will study cell structures and living systems while biologists develop data mining programs and design homes. As you’ll see in a case study discussed later, Dr. Cory Brouwer of the P2EP Project at the North Carolina Research Center has already made the leap with one foot in genomics and the other in bioinformatics.

     Businesses are unknowing practitioners of the New Biology as they increasingly cross industry sectors seeking more scientific and efficient methods of operation to produce food for the global marketplace. For example, in the agribusiness sector, Circle S Ranch in Union County uses ecologically friendly, sustainable operations in raising live poultry. Similarly, Simpson’s Eggs subscribes to science-based farming methods designed to ensure hen welfare. These companies are profiled in companion agribusiness profiles in the magazine.

 

Food: Plant Pathways and Plant Genomics

     Plant pathways and plant genomics are expected to be leading players in the biology of the future. Americans may not realize the extent of the world’s food shortages. The Food and Agriculture Organization of the United Nations estimated that 923 million people were undernourished in 2007, the most current data for the NRC report. The New Biology promises the world faster growing, less expensive and more nutritious sustainable plants.

     Genes of these super-efficient plants will be identified through quantitative trait mapping. Using what the NRC report calls genetically informed breeding, the genetic sequence of millions of plants can be determined from seeds and seedlings, not after their full life-cycle rotation.

     Biologists are now considering breeding plants with an alternative photosynthesis pathway. Dry climate plants are less efficient in turning carbon dioxide into carbohydrates. If they were bred with a more conventional photosynthesis pathway, the adaptation could increase photosynthesis rates in most of the world’s food crops.

     Within genomics is the sub-specialty of metagenomics or environmental genomics. Its purview includes temperature, moisture, light, viruses, bacteria, insects, fungi, birds and other factors. Studying plant-insect or plant-bacteria interactions could prove beneficial to crop yields. There is much to learn from these associations.

     “Ninety-five percent of all bacteria on earth are invisible to us,” says UNC Charlotte’s Lawrence Mays, chair of UNC Charlotte’s Department of Bioinformatics and Genomics. “That’s because we can’t culture them in a petri dish.” But genomic scientists can extract DNA from bacteria samples and examine their genetic profile. The field has built up a sizable library of its bacteria findings.

 

Climate: Major Environmental Issues

     The New Biology faces two major environmental issues: diagnosis and treatment. No single federal agency, scientific community or philanthropic foundation can develop a comprehensive set of tools to diagnose our ecosystem. At present there are eight federal agencies and departments that monitor our air, water, forests, soil and carbon dioxide levels. Even with that level of scrutiny there are mismatched datasets that make it difficult to detect trends or make comparisons.

     In regard to treating at-risk ecosystems, the NRC report does not quibble: “We do not currently have the tools needed to manage the biosphere.” There has been some progress in removing carbon from the atmosphere and in the growing subfield of restoration, but here the New Biology is in its early stages.

     Long-term and effective measurement and repair of our natural resources will require the combined efforts of biologists, engineers (civil, environmental and systems), mathematicians, modelers and computational scientists.

 

Energy: Biofuel Alternatives

     Most of the worldwide increase in energy demand is coming from rapidly developing economies like India and China. Three-quarters of their needs are met with fossil fuels. Worries about fossil fuel depletion and pollution are longstanding.

     Old Biology reminds us that the world’s first fuel was plant material, now referred to as biomass. The challenge for New Biology is to find plants that produce the most biomass with the least input of fertilizer and water and the least impact on the land needed to grow food. Corn accounts for most of the biofuel produced in the United States.

     “In parts of the American Midwest, 100 percent of the corn crop is used to make ethanol,” says Brouwer.

     The New Biology regards corn as a first generation biofuel. Second generation biofuels with higher alcohol content are now within reach. Crops in line to take away corn’s crown are sugarcane, sweet sorghum, switchgrass and miscanthus. Agricultural and forestry byproducts are also in the race.

 

Health: The Big Question

     Present day health and medical decisions are often based on probabilities. We abstain from high calorie, high cholesterol foods because of the high probability of heart disease. Probabilities are derived from populations and apply to some, not all, people. Understanding how an individual’s unique set of genes and an equally unique environmental history relate to the person’s health risk, disease susceptibility and response to treatment “is a challenge well beyond current capabilities,” according to the NRC report. In other words, neither genomics nor the New Biology is presently in a position to answer the smoker/athlete question.

     New variables have been found that make the question even more complex. Altitude, diet, exercise, exposure to sunlight and chemicals, as well as air- and surface-borne viruses and bacteria all influence the connection between our genes and our traits. New Biologists now think that the genes of each microbe that lives and works inside us also influence our development. Few of those connections have been studied.

     Despite the sheer complexity of this vast web of interconnections, genomic scientists have made progress. They have identified large numbers of human and microbial genetic variations and environmental factors that are associated with specific diseases. However, association or correlation does not mean causation.

     Causation will inevitably follow and genomics will move us from treatments based on statistical probabilities to treatments based on each individual’s specific circumstances. Individualized medicine and individualized nutrition are on the horizon. Experiments using fruit flies, Arabidopsis, mice, sea urchins and other model organisms will uncover networks, systems and pathways that are similar to humans. The journey of a thousand miles begins with a few genomic baby steps.

     The gap between research and application in biology and medicine is extraordinarily long. We are dazzled by advances in technology and frustrated by decades of tiny steps in biology.

     Yet the tortoise slogs forward. Scientists once thought that one gene mutation caused one cancer. They now follow a finite number of pathways from genes to disease. The Plant Pathways Elucidation Project and other collaborations emphasize nutrition and disease prevention, not crop productivity. The humble Arabidopsis is doing its part to move society from treatment by probabilities to individualized medicine.

 

 

Case Study: NCRC’s P2EP Project Fuses Plant Science With Human Health

     The NRC report writers make clear that plant pathways and plant genomics are expected to be leading players in the New Biology. Genomics is the study of genetics and biology.

     Genomics examines the interplay of genes with each other, the environment and human lifestyle factors. Genetics, on the other hand, looks at specific genes and traits and how they are passed between generations. Genomics may be able one day to unravel why a cigarette smoker who abhors exercise and overindulges lives to be 90, while a non-smoking health-conscious marathon runner dies at age 40 of a heart attack. By including variables such as diet, exercise and smoking under its research umbrella, genomics may one day be able to prevent cancer and heart disease.

     Genomic scientists moved closer to cancer prevention when they discovered that a wide array of genetic mutations grew and developed into the same cancer in different patients. Different mutations, different people, the same cancer and a finite number of pathways between genetic glitch and disease. That discovery had immense practical significance.

     “Rather than designing dozens of drugs to target dozens of mutations, drug developers could focus their attention on just two or three biological pathways,” suggests the National Human Genome Research Institute. “Patients could then receive the one or two drugs most likely to work for them based on the pathways affected in their particular tumors.”

 

Personalized Approach

     That personalized approach to better health is one of the factors motivating Dr. Cory Brouwer and his team at the North Carolina Research Campus in Kannapolis. Brouwer is an associate professor of bioinformatics and genomics at the University of North Carolina at Charlotte (UNCC) and part of the P2EP leadership team. His current interest concerns pathways in plants, and the labs at the North Carolina Research Campus proved ideal for this type of research. Brouwer’s mission is to learn how plants can produce better nutrients.

     Brouwer envisions a personalized nutrition. “It should come as no surprise that our nutritional needs are different from person to person because of our genetics,” he said. “We may someday sit down with a nutrition consultant who informs us that, based on the sequence of our genome, we need to be eating veggies with vitamins X, Y and Z and probably none of M, N and O. All vitamin supplements would become My-One-A-Day.”

     Brouwer hopes to achieve that goal through the Plant Pathways Elucidation Project or P2EP (pronounced “Pep”). The $1.5 million, four-year collaboration was launched this summer. Participating are UNC Charlotte’s Bioinformatics Services Division, North Carolina State University’s Plants for Human Health Institute and UNC General Administration. Industry leaders include the David H. Murdock Research Institute, Dole Nutrition Research Laboratory, General Mills and the N.C. Research Campus.

     The program addresses the overarching theme of “plant pathways” which are a series of chemical reactions in plants that help them to make the compounds they need to survive and adapt to environmental stressors such as disease or climate change. Each chemical reaction forms a part of a “pathway” to the formation of a specific compound, because it’s the natural path a molecule takes when changing from one form to another.

     Ultimately, the pathway leads to a new product like an amino acid, phytochemical or a type of fiber. Having been created to help a plant survive its own health risks, these newly formed compounds are often beneficial to human health when consumed. A primary goal of the P2EP program is to identify and map plant pathways in food crops—that is, decode the steps taken to produce the beneficial compounds—and better understand how they function. The P2EP project will conduct research on four foods—blueberries, strawberries, oats and broccoli—and mine data to generate a research knowledge base.

     “We’re mainly interested in metabolic pathways for this project,” says Brouwer. “These are a series of chemical reactions that occur within the cells. We elucidate the pathway by identifying the specific enzymes and chemical reactions that the plant is using to produce compounds important to nutrition.”

     Presently little is known about plant pathways. It’s surprising that neither nutrition nor edible plants have been the main focus of plant science research. Factors that affect plant yield like disease and drought resistance have always topped the research agendas, not nutrition.

     The flowering weed, Arabidopsis, has been the model organism for genomic research, not the four P2EP plants. Like the fruit fly of biological research, Arabidopsis is small and grows quickly. It also has a small number of genes and was the first plant to have its genome sequenced. Despite its fame, Arabidopsis is inedible.

 

Tools for Agribusiness

     Missing from previous plant genomic research have been the tools needed to produce nutritious fruits and vegetables. “Genomic sequencing is of no use to plant breeders until we connect those sequences to traits and markers that fruit and vegetable breeders can use,” Brouwer points up.

     Of the four plants studied in P2EP, oats may be America’s most neglected crop. Although it is the vital ingredient in cholesterol-lowering oatmeal and General Mills’ Cheerios, oats are no longer produced in the United States. They are raised only as a rotational crop in Canada. Corn and soybeans dominate U.S. agriculture.

     Beyond identifying and mapping plant pathways in food crops—decoding the steps taken to produce the beneficial compounds and understand how they function—the project is already producing terabytes in a knowledge base which Brouwer says will require “bioinformatics expertise and high performance computing to do the analysis that will lead to new and exciting discoveries.”

     Generating a knowledge base dedicated to plant pathways research from around the world first requires compiling the data to populate it, and that’s what Brouwer’s project is accomplishing. “The knowledge discovered within this project will be made available online to the public and the scientific community,” he says.

     “The Plant Pathways Elucidation Project represents the way big science can solve big problems for society—collaborations across disciplines involving industry and academia,” concludes Brouwer.

     Mary Ann Lila, director of the North Carolina State University’s Plants for Human Health Institute at the North Carolina Research Campus and a member of the P2EP leadership team, sums it up: “By answering the questions of how, why and what healthy plant compounds are produced, we’ll be able to advance scientific research, create opportunities for industry and consumers, and ultimately enhance human health.”

 

Photo by Fenix Fotography www.fenixfoto.com

 

Pete Prunkl is a Greater Charlotte Biz freelance writer.
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