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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology 3 Recommendations and Goals: New Horizons in Plant Genomics “Our greatest responsibility is to be good ancestors.” Dr. Jonas Salk THE FUTURE OF PLANT GENOME RESEARCH Plant science today lies at the nexus of potential solutions for global problems that are challenging a human population of more than 6 billion people today and that is projected to reach 9 billion by 2054 (United Nations 1999). Plants are extremely important sources of food, fiber, energy, and animal feed, yet plant biologists are only beginning to understand the fundamental principles of how plants grow and develop; how they cope with daily, seasonal, biotic and abiotic changes in their environment; how they participate in complex communities in diverse ecosystems; and how they evolved. Provision of adequate food and nutrition, expanded alternative energy sources, and sustainable environmental stewardship will require the development of new technologies for agricultural solutions that rest on detailed scientific knowledge. An understanding of the principles underlying plant growth, development, and reproduction will enable scientists to play a role in securing global health, the global economy, and the global environment by providing new options for improving productivity and reducing the environmental footprint of agriculture. The key to understanding those principles is basic research done in the context of the revolution of genome-based science. The committee strongly recommends that the next wave of National Plant Genome Initiative (NPGI) research should have as its top priority innovative, competitive peer-reviewed basic science aimed at detailed and system-wide understanding of the functions of individual genes, how those functions are
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology connected in networks, and how they control plant growth, form, function, performance, and evolution. The last 10 years have witnessed an explosion of knowledge regarding the various individual pathways that control plant growth and development. Biologists now better understand the principles underlying how plants perceive changes in their ambient environment; how they respond to pathogens; how they build flowers, leaves, and roots; and how various classes of hormone receptors direct plant growth. Several plant genomes have been sequenced, a few of which were sequenced to high quality. These discoveries, coupled with continued genome sequencing and resequencing, are the springboard for the next 10 to 20 years, a time during which fundamental research would have the definition of a plant that is more than “the sum of the parts” as its goal. Because of the federal research and development investments made over the last 20 years, plant biology is at the doorstep of an era of unprecedented large dataset collection, systems-wide analyses of those data, model building, and ever more precise hypothesis testing. The fruits of this research will be deeper understanding of how plant genomes condition important traits. However, the current knowledge is simply too underdeveloped, and translation of that knowledge is too costly or too imprecise, for the majority of desired applications. Thus, NPGI should aim to produce knowledge and tools for efficient trait modification and technology leaps so that genomic information can be translated effectively into environmentally sustainable products of benefit to humankind. The committee recommends the following guiding principles to achieve those goals. The committee strongly endorses the conclusions of the 2002 NRC report, The National Plant Genome Initiative: Objectives for 2003–2008, that studies aimed at defining core concepts of molecular and developmental plant biology are best undertaken rapidly and efficiently in model plant systems. Basic discovery that can be most rapidly and efficiently done in these systems should receive high priority. The committee advocates deep investment in the broadest possible set of genomics tools for these carefully selected systems. These systems would be chosen on the basis that they can provide vital paradigms that inform many other aspects of NPGI and can maximally leverage continued, independent investments in Arabidopsis genome science. Because the diversity of plant form and function utilized by humans is very broad, the committee strongly endorses the approach that parts of the overall genomics toolkit be deployed to investigate specific aspects of plant tissue and organ development, environmental adaptations, or biochemical processes that are not well represented in core model species. This will include a great deal of genome sequencing along the entire plant phylogeny to inform comparative func-
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology tional studies. However, descriptive functional studies aimed at gathering parallel datasets merely because they are derived from crop species would not be a good use of resources and are best avoided. The committee recognizes the critical need for the development and deployment of field-robust, high-resolution genotyping and phenotyping methods for use in molecular-assisted plant breeding across a broad swath of crops. These methods will require DNA sequencing (though certainly not always full genome sequencing) and substantial population sampling to define informative markers. They will require technological breakthroughs at genotype and phenotype levels to produce simple, robust methods available to plant breeders in the United States and around the world. These activities are crucial if the ultimate benefit of the NPGI discovery engine is to be realized. Hence, a scaffold of genomic tools is needed in each of the major crops in order to translate model organism concepts to them. The committee suggests that the priorities for NPGI and associated plant sciences be framed towards addressing the large challenges facing humanity, including bioenergy, climate change, sustainability, and human nutrition. The committee envisions the growing enablement of genomic tools, systems biology, and trait modification capabilities in a wider range of species than those currently emphasized. However, investments in those tools are only justified when there is a clear social goal and when the technologies for data collection, hypothesis testing, and trait modification become reasonably efficient and robust. The committee’s nine recommendations for NPGI priorities in the future are listed in Box 3-1. Each recommendation has a set of goals on three different time horizons: The 5-year goals represent immediate, pragmatic “next steps” in plant genome science, 10-year goals require significant development of new tools and resources to enable transformative solutions to real world problems, and 20-year “achievements” reflect the committee’s desire to define some admittedly long-range, high-risk, high-reward areas that would significantly alter society’s ability to understand how plants work. TOOLS FOR PLANT GENOME RESEARCH IN THE 21ST CENTURY One of the most remarkable impacts of genomics projects is the development and application of facile technologies that allow the global analysis of cellular components, including genes, proteins, and metabolites. After their invention, high-impact technologies are disseminated for use by individual laboratories and by “data production centers” that generate large amounts of data to benefit the entire scientific community. The number of hypothesis-driven, single investigator
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology BOX 3-1 Overall Recommendations RECOMMENDATION 1: Expand plant genome sequencing, plant-associated microbial sequencing, and plant-associated metagenome sequencing, and associated high quality annatation by (a) using the Department of Energy’s Joint Genome Institute’s sequencing capacity to generally serve plant science and (b) empowering individual principal investigators or collaborative groups to access and utilize next generation sequencing technologies for a broad spectrum of genomics and metagenomics discovery. RECOMMENDATION 2: Develop “omics” resources and toolkits at high resolution in a few, carefully chosen plant species, including expansion and deeper investment in currently leading model species. RECOMMENDATION 3: Develop “omics” resources at a broader, shallower level across a number of additional species to (a) expand the phylogenetic scope of functional inference, particularly when this is justified to test clearly specified hypotheses, (b) understand physiological and development processes to a depth that is not feasible in the model systems, and (c) provide the foundation to improve U.S. competitiveness of important crop and tree species. RECOMMENDATION 4: Use system-level approaches to understand plant growth and development in controlled and releveant environments, with the goal to create the iPlant, a large family of mathematical models that generate computable plants genuinely preditive of plant system behaviour under a range of environmental conditions. RECOMMENDATION 5: Increase the understanding of plant evolution, domestication, and performanace in various ecological settings via investment in comparative genomics, and in the metagenomics of living communities of interacting organisms. RECOMMENDATION 6: Enable translation of basic plant genomics toward sustainable deliverables in the field, and continue to use NPGI as a foundation for new, agency-specific, mission-oriented plant improvement programs. RECOMMENDATION 7: Develop and deploy sustainable, adaptable, interoperable, accessible, and evolvable computational tools to support and enhance Recommendations 1–6. RECOMMENDATION 8: Improve the recruitment of the best, broadly trained scientists into plant sciences. RECOMMENDATION 9: Promote outreach on plant genomics and related issues that are critical to educating the American public on the value of genomics-based innovations.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology research projects will have to grow so that creative scientists can avail themselves of these technologies and capture the resultant benefits for society. It is equally imperative that groups of investigators, whether within or across institutions, be supported for collaborative projects when they are scientifically warranted. Collaborative group formation, however, should not be a requirement for funding because these can be “forced marriages of convenience” that are often not synergistic in their output. Finally, the plant genomics community has benefited from the establishment of high-throughput production centers and will continue to do so. These are particularly well suited to generation of data and resources for use by the broader community. In principle, production centers that produce physical or information resources have the advantages of higher efficiency and uniform quality control standards to ensure that useful reagents and information are produced. The guiding principle would be that the quality of information produced by a resource center be equal to or greater than that typically produced by an individual research laboratory. Examples of genomics technologies that have had significant impact on the plant biology community include T-DNA and transposon tagging strategies, DNA microarrays, and mass spectrometry. These technologies are now sufficiently widespread that they are accessible to most researchers for individual experiments. In plant sciences, the accessibility of these technologies can be largely attributed to NPGI and the Arabidopsis 2010 Project of the National Science Foundation (NSF). At the same time, these technologies also are used in production projects. For example, the ends of T-DNA and transposon insertions are sequenced to locate the position of each in the genome. TILLING collections now exist for various species, and they allow investigators to screen for point mutations using polymerase chain reaction. DNA microarrays are used for large-scale analysis of gene expression and mapping transcription factor binding sites. Mass spectrometry is readily used for large-scale mapping of protein-protein interactions. DNA Sequencing: The Basis of Genomics Recognizing and taking advantage of opportunities to “upgrade” large-scale datasets as new, quantitative, rapid, and cost-effective technologies are released is critical to NPGI. It is also important that NPGI lead the development of such technologies, which would then drive their deployment via the mission-based member agencies like the U.S. Department of Agriculture (USDA) and the U.S. Department of Energy (DOE). An example of opportunities for “data upgrades” is the new, high-throughput next-generation DNA sequencing technologies that have emerged in the last year—for example, pyrophosphate sequencing (454 Life Sciences™/Roche) and localized cluster sequencing (Illumina, Inc.). Others will no doubt emerge very soon.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology The new technologies grew out of a specific funding mechanism from the National Human Genome Research Institute (NHGRI) to support the goal of sequencing a human genome for $1,000. The technologies have had enormous impact on the sequencing of new genomes and have profoundly altered the ability to resequence, at a huge savings, natural variants of species where a reference genome sequence already exists. The new, next-generation DNA sequencing technologies will revolutionize the ability to map transcribed regions and transcription factor binding sites across a genome and to address how these phenotypes change over developmental time and in response to various stresses. Resequencing technologies can open new vistas in creative analysis of natural variation and evolution, and in understanding the complexity of organisms present in environmental samples of plants and their associated microorganisms. In turn, next- generation DNA sequencing technologies have created demand for new informatics tools that can deal with the collection and assembly of small DNA fragments. This interplay results in a familiar and compelling cycle—important new technologies drive the creation of new ancillary technologies and create horizons for new biological experimentation that were previously unreachable, leading to new levels of detailed experimental understanding. Thus, the committee can now credibly propose to use genomics to understand the principles underlying plant genome structure and evolution. Understanding how plant genomes expand and contract through polyploidization, segmental duplication, and subsequent loss or silencing of genetic information, for example, is now within reach. Furthermore, what were once puzzling and unappreciated features of plant genomes, such as the very high proportion occupied by transposons in some lineages, can be understood within a solid theoretical framework with genome sequencing on the scale recommended in this report. The committee does not, however, anticipate that physical chromosome maps and complete draft sequences will be required for all projects. Judicious choices for genome sequencing, in addition to those species listed below in Table 3.1, should consider how polyploidization has led to variable plant gene function and the evolution of novel traits of interest. RECOMMENDATION 1: Expand plant genome sequencing, plant-associated microbial sequencing, and plant-associated metagenome sequencing, and associated high quality annotation by (a) using the Department of Energy’s Joint Genome Institute’s sequencing capacity to generally serve plant sciences and (b) empowering individual principal investigators or collaborative groups to access and utilize next generation sequencing technologies for a broad spectrum of genomics and metagenomics discovery.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology As noted in Chapter 1, genome sequence is the raw material for functional, evolutionary and translational tool development at the center of plant genome sciences. Plant sciences will benefit from the generation of the first “reference genome” sequences for a growing number of species that define key points in plant evolution. The next-generation sequencing will enable both “reference genome” sequencing and resequencing for purposes of population and evolutionary genomics (see also below). As an example, it is likely that sequences from closely related species will constitute a powerful way to inform the functional biology of target genomes (from patterns of evolutionary conservation of sequence motifs, functional domains, and so on). Hence, for every species whose genome is chosen for a reference sequencing project, parallel sequence analysis of a related taxon of appropriate evolutionary distance (something on the order of 30 to 50 percent divergence at silent sites being optimally informative) would be appropriate. Furthermore, the metagenomes of cultivated plants and plants in natural ecosystem communities will provide rich arenas for future discovery of important interorganismal associations that have positive or negative impact on plant performance (NRC 2007a). Metagenomics has been embraced by NIH, and has led to a major program on the human metabiome. A similar large-scale investment in plant-associated metagenomics is justified because of the diversity of plant-associated microbial communities and their impact on plant productivity. For example, the communities of microorganisms associated with candidate perennial biofuels crops, in monoculture or in more natural assemblages, are not well understood. As another example, the rhizosphere community, both microbial and animal, can influence root growth and development. Certain microorganisms can protect plants from other pathogenic microorganisms. Hence, a merging of metagenomics with root genomics would be rewarding. Thus, the committee strongly endorses the recommendation that NPGI make major investments in both plant genome and large-scale metagenomics sequencing efforts. The unique role played by the Department of Energy’s Joint Genome Institute (JGI) in the service of NPGI is critical. Although there are several high-throughput genome centers devoted to the missions of NHGRI, only JGI has plant biology as a central component of its mission. JGI has established a peer-reviewed policy for high-impact reference plant genome sequencing, which it has implemented successfully (see Chapter 2). The economies of scale gained from JGI’s expertise and throughput, especially with their addition of next-generation sequencing capabilities, is unlikely to be matched by another sequencing center that has a deep interest in plant genomics. JGI is thus uniquely placed for the development of projects that combine traditional Sanger sequencing with the next-generation sequencing technologies that will lower the costs of reference sequencing considerably and allow economies of scale for resequencing projects. Table 3-1 provides a list of species for
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology which one could argue a strong case for inclusion for NPGI genome sequencing plans in the next 10 years of NPGI. Even at the economies of scale provided by combining JGI’s throughput and next-generation sequencing, the sequencing of one reference genome from each of the species listed above will be costly. Therefore, use of other criteria to prioritize the list is necessary. The committee’s recommendation for criteria to prioritize organisms for sequencing, as applied to different sets of biological and technologic issues, can be found in Recommendations 2–4 below and in the 2002 NRC report. JGI should also seek to upgrade its basic and limited annotations, preferably via collaboration with groups containing the relevant expertise or by expanding its own activities in this area. Interaction between JGI and the NSF’s Plant Cyberinfrastructure awardees could be synergistic in this regard. The committee therefore considers it highly desirable that DOE continue to take a broad view of JGI’s unique position in the plant science community. It is critical to the success of NPGI that JGI continue to serve a broad remit for sequencing and resequencing of plant genomes, a remit not limited to only the sequencing of plants that are directly important to bioenergy production. To narrow JGI’s mission would imperil a successful pillar of the NPGI infrastructure. The next-generation sequencing technologies and supporting bioinformatics will also make resequencing of many different genotypes of small genome species a reasonable goal for individual principal investigators (PIs) or for groups of PIs. Resequencing is a critical new tool in the genomics toolkit because it allows scientists to understand how individuals vary at the DNA level, and how that variation shapes differences between individuals of the same species, and across short evolutionary distances by sequencing individuals of closely related species. Resequencing is especially important in the context of understanding evolutionary mechanisms and the natural diversity of plant form and function. Resequencing is already having a powerful impact on Arabidopsis genomics (Clark et al. 2007; Kim et al. 2007), and a project underway to resequence many rice relatives will certainly have similar impact in the understanding of rice evolution and domestication. It seems reasonable that the JGI would take the lead on generating a broad swath of new plant genome sequences, because plant science still requires many high-quality draft sequences to serve as reference sequences for those species and branches of the evolutionary tree. In addition, other existing large-scale sequencing centers could be recruited to participate in NPGI activities. The costs of sequencing will likely drop, and many of the major crop species could be sequenced. Furthermore, multiple reference sequences might be necessary to cover the major halpotypes of a given species, if the haplotypes are divergent enough from one another. By contrast, resequencing efforts could be done by individual laboratories with access to the new sequencing technologies, or consortia of investigators
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology interested in specific questions in population, evolution, and ecology that require a large resequencing component. Indeed, the Arabidopsis Landsberg-er and Cvi-0 accessions have been resequenced in two weeks each at a fraction of the cost of the original reference Col-0 sequence (J. Ecker, Salk Institute, personal communication, October 20, 2007). Goals for Sequencing (Recommendation 1) 5-year goals Sequence the genomes of 25–50 strategically chosen plants and resequence the genomes of hundreds, if not thousands, of wild accessions of the plants chosen for the full “omics” effort. These sequencing programs would be accompanied by standards-based annotation. 20-year achievements Hundreds of reference plant genomes will be draft sequenced to high coverage and annotated for comparative purposes and development of mapping tools. These will blanket the plant evolutionary scale. Tens of thousands of plant genomes, or more, will exist as annotated resequences. “Omics” Resources and Toolkits RECOMMENDATION 2: Develop “omics” resources and toolkits at high resolution in a few, carefully chosen plant species, including expansion and deeper investment in currently leading model species. All well-planned genome initiatives involve systematic development of resources that enable next-generation experimentation. NPGI is no exception. These resources include tools for genomics, epigenomics, transcriptomics, proteomics, metabolomics—often referred to collectively as “omics” tools. The tools result from large datasets that, for example, catalog mRNAs or small RNAs, proteins, or metabolites. But they also result in experimental materials, such as mutant plants, cDNA clones, and recombinant proteins. Development of omics tools most commonly requires high-throughput, computationally intense methods, and it is technology-driven. As computation and technology advances, so do the quality and quantity of omics data and resources. The utility of omics tools depends on accessibility and applicability to a broad community of researchers.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology TABLE 3-1 Desirable Reference Genome Sequences Not Currently Funded. This Table Lists Other Future Projects of Direct Relevance to Food, Feed, and Fuel Needs of the United States Species Common Name Genome Size (Gb) Notes Phaseolus vulgaris Common bean 0.5 An important crop in its own right, Phaseolus is also an unduplicated outgroup for the recent soybean tetraploidy. Pinus taeda Loblolly pine 20 Wood crop, forest resources. Other gymnosperms (for example, spruce) also desirable, but note extremely large genome size. Pennisetum glaucum Pearl millet 2.7 Drought tolerant grass, cereal of “last resort.” Panicum capillare Diploid switch grass 0.5 A genetically tractable diploid relative of the tetraploid Panicum virgatum (switchgrass), a leading biofuel crop. Triticum aestivum Hexaploid bread wheat 17 Hexaploid wheat and its diploid relatives, which are major sources of nutrition around the world and a system for understanding genetic effects of domestication and polyploidy. Aegilops speltoides, Triticum monococcum, Aegilops tauschii Diploid wheats related to progenitors of bread wheat 2-4 Malus x domestica Apple 0.7 Along with peach, these two rosaceous crops are at strategic phylogenetic distances for intrafamily sequence comparisons Fragaria vesca Strawberry 0.2 Musa acuminata Banana, plantain 0.6 Outgroup for grasses and the grass-specific paleotetraploidy, and therefore key to understanding important crops, especially in developing world. Vulnerable through limited genetic diversity. Citrus sinensis Sweet orange 0.4 Major U.S. crop that is highly sensitive to frost. Genome sequencing could aid genetic improvement for cold resistance. Marchantia polymorpha Liverwort 0.4 Primitive land plant that will assist in understanding the polarization of changes along the stem leading to angiosperms and gymnosperms. Manihot esculenta Cassava 0.8 Source of carbohydrates in developing world. Sample sequencing project is underway, with no full genome commitment
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology Species Common Name Genome Size (Gb) Notes Gossypium sp Diploid cotton; polyploidy cottons >1.0 Valuable fiber crop is polyploid, with diploid relatives. Sample sequencing project is underway, but no full genome commitment. Saccharum officinarum, Miscanthus sinensis Sugarcane, Chinese silver grass 2-3 Rapidly growing C4 grasses with potential for biofuel feedstocks. Sugarcane is octoploid, Miscanthus is diploid, also providing a rich system for studying polyploidy. Citrullus vulgarus Watermelon 0.5 Would provide a cost-effective reference genome for cucurbits Lactuca sp. Lettuce 2.3 Diverse complex of species provides rich gene pool for breeding hardier varieties. Solanum tuberosum Potato 0.9 Although related to tomato, potatoes were independently domesticated. Important comparators within Solanaceae. Solanum chacoensis Wild potato 0.6 Ipomoea sp. Morning glory 0.7-1 Morning glory, diploid closely related to sweet potatos, which are typically polyploid. Potential genetic model system for tuber formation. Helianthus anuus Sunflower 2.4 Important source of edible oil worldwide Antirrhinum majus Snapdragon 1.6 Genetic model system that would be invigorated by genomic resources Medicago sativa Alfalfa 0.9 Forage crop, tetraploid relative to M. truncatula model system Boechera holboellii Rockcress 0.2 Model system for asexual (apomictic) reproduction in plants, with an international user community. Closely related to Arabidopsis. Useful, integrative, Web-based computational resources that allow the broader community of scientists to derive high value and to form testable hypotheses are a critical component of a full omics effort. For example, what good is an omics project to assemble a deep catalog of molecular and metabolic responses to drought stress if plant biologists working on important problems of drought stress cannot access, synthesize, understand, and analyze the data? Furthermore, these Web-based
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology however, those programs are unlikely to meet the dramatically rising demand for scientists with interdisciplinary expertise that includes bioinformatics (Zauhar 2001). The NRC report Rising Above the Gathering Storm (NRC 2007b) recommended increasing the number of U.S. citizens pursuing graduate study in “areas of national need” by funding 5,000 new graduate fellowships each year. NPGI should build mechanisms to ensure that the number of graduate and undergraduate students with rigorous training in both biological and quantitative approaches to plant genomics is sufficient to support a thriving research and development job environment in both the public and private sectors. By leading with new opportunities for graduate support in bioinformatics and computational biology within the context of plant genomics, NPGI could bolster the image of plant science as an exciting alternative to the biomedical fields for ambitious and creative students. Students trained in engineering and computational sciences might represent an untapped resource whose skills and inclinations could make them valuable contributors to plant genomics. In particular, engineers are familiar with systems that behave imperfectly, and their systems-level perspective has already enabled important strides in modeling biological regulatory circuitry (Wiley et al. 2003). Collaborative relationships with faculty in engineering could lead to unique training opportunities. NPGI researchers interested in establishing connections with colleagues in engineering might consider the emerging field of synthetic biology (Endy 2005) as a possible example of common ground. As a growing number of Ph.D. umbrella programs require a course in genomics and bioinformatics of all their students, it is incumbent upon NPGI-funded faculty members to insist on standards in their institutions’ training programs that will meet their research needs. NPGI-funded PIs could be encouraged to offer modules or other shared teaching formats in these courses. Eventually, most incoming graduate students will be able to fulfill requirements in bioinformatics through their undergraduate education, and important inroads have already been made in developing bioinformatics curricular materials suitable for even introductory-level biology courses (Honts 2003; Campbell and Heyer 2007). However, until those fields trickle down to become standard course offerings at the undergraduate level, graduate programs will need to provide them to the incoming students. Summer internships are one path by which interested undergraduates can become acquainted with, and gain proficiency, in bioinformatics and computational biology. Table 3-2 lists several such programs. The NRC report BIO 2010 advocates encouraging all students to pursue independent research as early as possible in their career (NRC 2003). These research experiences reinforce, clarify, or increase students’ interest in postgraduate education (Lopatto 2004; Seymour et al. 2004) and can result in enhanced confidence in
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology TABLE 3-2 Representative REU Programs and Summer Internships for Undergraduates in Computational Biology, Bioinformatics, and Systems Biology Field Institution Website Computational and systems biology Iowa State University http://www.bioinformatics.iastate.edu/BBSI Computational and systems biology Massachusetts Institute of Technology http://csbi.mit.edu/website/outreach_programs/summerintern Computational biology University of Connecticut Health Center http://www.nrcam.ucnh.edu/news/positions.html#intern Bioinformatics/computational biology University of Maryland Baltimore County http://www.umbc.edu/SPCB/ Bioinformatics/genome science University of Southern California http://cegs.cmb.usc.edu/academics/bigs/BIGS.html Computational biology/ bioengineering/Bioinformatics University of Pittsburgh http://www.ccbb.pitt.edu/BBSI/index.htm Bioinformatics/bioengineering Virginia Commonwealth University http://www.vcu.edu/csbc/bbsi/ Bioinformatics and computational biology Cold Spring Harbor Laboratory http://www.cshl.edu/URP/nsf~reu Computational genomics Kansas State University http://www.kddresearch.org/REU/Summer-2003/announcement.html Fungal genomics and computational biology University of Georgia http://www.genetics.uga.edu/undergrad_fgcb.html Bioinformatics Loyola University, Chicago http://reu.cs.luc.edu Systems biology Harvard http://sysbio.harvard.edu/csb/jobs/undergraduate.html Bioinformatics California State University, Los Angeles http://instructional1.calstatela.edu/jmomand2/ Genomics/bioinformatics J. Craig Venter Institute http://www.jcvi.org/education/internship.php Bioinformatics Greater Philadelphia Bioinformatics Alliance http://www.gpba-bio.com/educ_internships.asp attributes related to “thinking and working like a scientist,” gains in communication and practical skills, and enhanced preparation for graduate school (Seymour et al. 2004). Students also acquire realistic insights into the process of scientific inquiry (Gafney 2001). However, undergraduate research experiences do not appear to attract significant numbers of previously uninterested students to a career that requires a postgraduate degree (Hunter et al. 2006; Lopatto 2004; Seymour et al.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology 2004). One important caveat pertains to programs that recruit first-year students from underrepresented groups: Such programs might indeed stimulate a student’s interest in graduate school, because these students are among those least likely to have had exposure to the idea of graduate school as an option (Seymour et al. 2004). NPGI could promote, and then carefully monitor over time, the expansion of undergraduate research opportunities that result in an expanded and diverse plant genomics community, Students and faculty members alike cite the importance of dedicated mentoring as a key factor contributing to students’ positive responses to their research experience (Lopatto 2003). The primary mentors for many undergraduate research, though, are graduate students and postdoctoral fellows, who may have little or no experience in teaching or mentoring younger scientists, and who could benefit from a recently developed program (Handelsman et al. 2005) that has been validated for effectiveness at 11 institutions (Pfund et al. 2006). Introductory laboratory courses that engage students in interdisciplinary investigations in plant sciences and genomics are another avenue to promote student interest in research at a time when their career choices are still relatively fluid. Students might assimilate new information more effectively through inquiry-based, collaborative activities than through traditional classroom learning alone (Wood and Gentile 2003). Inquiry-based pedagogical activities in genomics that address significant, novel questions are under development by single institutions (Washington University 2005), by a consortium of small liberal arts colleges working together with Columbia University’s Genome Sequencing Center (Carleton College 2007), and by JGI. The Howard Hughes Medical Institute has recently initiated plans for a national genomics research course for undergraduate freshmen. Students from colleges and universities around the country will work collectively on the same research questions, sharing data and results (HHMI 2007). These innovative programs illustrate ways that education can be more fully integrated into NPGI-funded research. However, it is absolutely vital that already overburdened PIs, or groups of PIs, receive sufficient extra funds, beyond those required to perform their research in an increasingly competitive funding environment, to devote dedicated personnel to these endeavors. For example, NPGI could consider establishing a new category of PIs dedicated to education, as pioneered by the Howard Hughes Medical Institute through its teaching investigators program. Large plant genomics centers should hire full-time outreach coordinators by appointing professional education managers. Initiatives to be organized at this level could include summer-long funded research internships for community college and high school teachers who wish to develop inquiry-based activities that involve students in the practice of science. Dissemination of information about educational activities deemed successful, as assessed by rigorous outcomes-based metrics, should also be a higher priority for NPGI. One venue for sharing “what
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology works” is to hold sessions devoted to education at the large professional society meetings. By working more closely with the Botanical Society of America and the National Association of Biology Teachers, NPGI can reach thousands of members who teach at the undergraduate and precollege level. Plant Genomics, National Competitiveness, and International Collaboration International partnerships like those described in Chapter 2 provide opportunities for U.S. researchers and students to gain valuable experience in a foreign research setting. In an increasingly global scientific arena, U.S. competitiveness will be enhanced by training a cadre of young scientists who understand the advantages of different research environments, the scope of fundamental issues such as food security, and the challenges to national security posed by agricultural constraints. Grand challenge programs that are truly visionary will likely be international in focus, and will require researchers who can design creative and productive programs that are not limited by a single perspective. In this regard, NPGI could seek collaborative funding opportunities with various foundations that are concerned with global agricultural issues, as well other traditional international partners. The groundwork and personal connections that are needed to help structure successful international research programs are often fostered during the formative years of a scientist’s career. Such international research networks harness the creative energy of a young, mobile generation of scientists and the economic power of the emerging economies of Asia (specifically China and India) and of the European Union, the United States, and Australia to provide training, education, and research infrastructure, and to ensure public access to data and information. These considerations suggest a need to increase the opportunity for international training, particularly for our graduate students. For all of the adopted education recommendations (see below), NPGI should build robust and peer-reviewed methods for assessment. Furthermore, IWG agencies should require all NPGI PIs to report the previous educational background, citizenship, and subsequent career paths for every individual funded by an NPGI grant. NPGI needs to establish a mechanism to collect these data in a centralized location and a set of quantitative criteria by which goals for training can be articulated and measured against this dataset. Outreach RECOMMENDATION 9: Promote outreach on plant genomics and related issues that are critical to educating the American public on the value of genomics-based innovations.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology Many research programs include components to reach out beyond the scientific community and emphasize the importance of increasing the public understanding of science. Outreach programs in plant genomics are important because end users—food consumers, breeders, farmers, and others—are likely to apply or use products and tools of plant genomic research if they understand the value and benefits of those products and tools, and their potential risks. As with education, NPGI should build robust and peer-reviewed methods for assessment of any adopted outreach recommendations. Because the goals of such activities will determine the metrics to be used to measure success, the goals of the education and outreach activities have to be clearly defined. For example, if one goal of workshops for K-12 teachers and summer internships for high school students is to broaden the targeted populations’ understanding about plant science, genomics, and biotechnology, the conduct of rigorous surveys of participants’ knowledge before and after each program is necessary to assess the impact of the workshop. Longer-term assessment could include occasional follow-up questionnaires to document the broader impact of participation in the workshops on the science curriculum at the teachers’ home schools. For programs with an explicit focus on plant biotechnology, student attitudes about biotechnology could also be monitored before and after the activity or internship. Likewise, one common approach to K-12 outreach in science education is a short-term classroom visit or series of visits by a researcher. The visiting researchers might lead a hands-on activity or talk with the students about societal implications of their research. The goals of such visits are to generate enthusiasm among students for science, improve the image of scientists, and promote science literacy (Laursen et al. 2007). There is little direct evidence that classroom visits achieve those goals. One qualitative assessment of a best-case “scientist in the classroom” program documented some measures of success and several benefits and some potential costs to the graduate students who participate in the program (Laursen et al. 2007). Scientists who wish to develop an outreach program might not know how to do so effectively and might be unfamiliar with existing resources that could guide them and prevent unnecessary duplication of efforts. In the face of increasing time pressures on principal investigators, graduate students, and postdoctoral fellows, there is little sense in researchers “reinventing the wheel” with respect to outreach and pre-college education (Dolan et al. 2004). Additional support from NPGI for personnel explicitly trained in outreach who help PIs and graduate students to define, achieve, and further their outreach goals, including outreach to extension and breeder groups, is critical for the translation of NPGI science into tangible benefits to society. As has been observed (Labov 2006), “the kinds of experiences (or lack thereof)
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology BOX 3-2 The Partnership for Research and Education in Plants The Partnership for Research and Education in Plants, Biology (PREP; Virginia Polytechnic Institute and State University 2006), funded by NSF’s Arabidopsis 2010 Project, NIH, and the American Society for Plant Biologists, allows high school students to contribute to real research projects. PREP has involved over 10,000 students, 54 teachers, and 26 scientists in six states. It is the brainchild of the biology teacher, a plant geneticist, and a faculty-level outreach coordinator working together (Dolan et al. 2004). High school students design experiments to characterize novel Arabidopsis mutants. The student collect and analyze data on growth and development of the plant lines, and report the data in an online notebook that faciliates interactions with the partner researches (peers and professional scientists). PREP examplifies at least three of the four priniciples of instructional design advocated by a recent NRC report on successful laboratory exercises: 1) they are designed with clear learning outcomes in mind; 2) they integrate the learning of science content with learning about the process of science; and 3) they incorporate ongoing student reflection and discussion (NRC 2005b). in science that students encounter during their K-12 years will have direct consequences on what college-level instructors will be able to accomplish in their own classrooms and teaching laboratories.” By joining forces to expand implementation of an existing program such as the Partnership for Research and Education in Plants (Box 3-2), rather than cobbling together a forced activity lacking a well-considered rationale, NPGI investigators could have a national impact on high school education. Bringing Genomics to the Sustainable, Local, and Organic Agriculture Communities The communities of small-scale and organic farmers are expanding in both numbers and in economic and political clout, driven by rising consumer demand for sustainable and locally grown food. This market sector is likely to grow, especially if food transportation costs rise dramatically. Philosophical interest in plant genomics among these groups is likely to benefit from clear communication that genomic research is not necessarily tied to deployment of transgenic plants, and on tangible and relevant outcomes in the form of cultivars that are well suited for particular, local, and often low technological input, agricultural niches. The committee suggests that NPGI investigate creative mechanisms to translate its research into benefits for such growers. An example is the Public Seed Initiative at Cornell (Cornell University 2005), whose focus is on developing, maintaining, and distributing seeds for cultivars of fruits, vegetables, and grains adapted to the
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology needs of organic and local fresh-market growers. By continuing its current focus on applications of genomic tools to marker-assisted selection for diverse crops and traits, NPGI will also provide useful information to this grower community. For example, both large- and small-scale farmers benefit from markers that speed the development of cultivars with enhanced disease resistance. In addition, NPGI is poised to apply technological advances in metagenomics, metabolomics, and systems biology to characterize the complex interdependences among species that are considered important to various cultivation systems, including organic. For example, identification of microbial population structures and the nature of metabolites found in disease suppressive soil ecosystems will help to guide the development of agronomic practices that reduce the need for pesticide use. One interesting case could be investigation of permacultures. Permacultures have minimal need for fertilization, irrigation, or pesticide usage because ecological processes common to forestry ecosystems or agroecosystems are used to maximize the yield of edible species in perennial agroforestry and polyculture systems (Jacke 2005; Mollison 1988). To identify specific traits that are needed in new food crop cultivars, NPGI could take steps to engage small-scale farmers and relevant trade groups and to facilitate direct interactions between farmers, breeders, and researchers. This could entail interactions between genome scientists and producers to address genomics applications germane to this arena, and participation from producers to identify what portions of the genomics toolkit are most relevant to them and with respect to what traits, at extension events, county fairs, and local farmers’ markets. Since the officially sanctioned organic farming community has banned applications involving human directed recombinant DNA manipulations (for example, genetically modified organisms [GMO]; AMS 2007), even the most well-meaning efforts to create common ground between genomic researchers and organic farmers could be derailed by negative grower or public perceptions that simplistically equate plant genomics with genetically engineered plants and/or proprietary technologies owned by multinational corporations. By fostering a climate of enhanced understanding and promoting connections among researchers, farmers, small-scale seed producers, and nonprofit organizations, NPGI researchers might pave the way for acceptance among small scale growers of a variety of plant genomics technologies. Examples of a technology that NPGI might seek to further develop and communicate as part of this effort are improved forms of “all-native” or “cisgenic” transformation (discussed earlier in this chapter). These basic approaches need to be made efficient in a variety of species, improved so that mutagenesis during gene transfer is minimized, and made more precise via gene targeting and allele replacement capability. They also need to be publicly accessible (that is, not dominated
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology by private sector patents) so that localized, plant variety- and region-specific use is feasible. Ethical, Legal, and Social Issues in Plant Genomics In the Human Genome Project (HGP), ethical, legal, and social issues (ELSI) related to human genomic data and related technologies were recognized to have major impacts on how genomic information would be used in biomedicine. ELSI research at the National Human Genome Research Institute (NHGRI) began in 1990 to understand the social implications of genetic and genomic research. Its orientation has been consciously proactive, in that it seeks to identify “… problem areas … and solutions … before scientific information is integrated into health care practice” (NHGRI 2007). The ELSI program accounts for more than $18 million of the annual $485 million HGP budget. In contrast, there has been little ELSI-related activity in plant genomics research. Despite initial plans to the contrary (NSTC 1998) and reemphasis (NSTC 2000), only a narrower objective was retained under broader impacts of the NPGI, stating that “research is needed to identify methods for more effective communication with the general public” (NSTC 2003). To date, there has not been significant collaborative engagement with social scientists to conduct scholarly research on the causes and resolution of ELSI issues related to plant genomics (NSTC 1999, 2000, 2001, 2003, 2004, 2005, 2006, 2007). The lack of attention to ELSI programs from the NPGI is surprising in that it comes amidst growing controversies in the agricultural, forestry, and energy sectors about genetic technologies, particularly transgenic approaches, and in a political climate where public skepticism regarding the economics associated with government-subsidized ethanol production are becoming ever more important. Because of attendant costs and social controversies, issues that could be addressed via ELSI research have effectively removed GMO tools for translation of genomic knowledge into useful products from all but the largest commodity crops and the largest agricultural companies, and in only a subset of countries. GMOs have served as a focal point for analysis of a large number of ELSI issues that are growing in significance for agriculture (Serageldin 1999); these may logically spread to encompass all of genomics-enabled breeding in the future. The limited attention to ELSI issues by NPGI may have impacted public perception of plant genomics and associated biotechnologies. In the acrimonious GMO debate, most of the NPGI-funded genomics research community has been conspicuously quiet, even when the debate concerns substantive genomics issues. This may have helped to create space for those with strong political views, but weak knowledge of plant science, to dominate the social discourse (Vasil 2003),
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology promoting confusion on the part of the media and public. The plant genomics community could provide context for understanding the impacts of GMOs, in comparison to the effects of accepted practices of breeding and domestication, on plant genomes. Because fundamental advances in knowledge of plant genomes are likely to empower increasingly novel, innovative uses of genomic information, the opportunity cost to society from its limited ability to use transgenic approaches is likely to grow rapidly. Outreach on ELSI topics is an issue that the NPGI needs to confront. A next generation of teachers and scientists who are trained in both plant genomics and ELSI issues could contribute to resolution of genomics-related social issues, and thus play a valuable role in guiding the development of scientifically sound regulations. The outcome could have profound consequences for deployment of the products of plant genomics, and on laws that govern international trade. Potential ELSI issues of interest to NPGI include those listed in Box 3-3. Goals for Education and Outreach (Recommendations 8 and 9) 5-year goals Develop evidence-based metrics to assess educational and outreach programs. Enhance opportunities for graduate and undergraduate students to become proficient in the theory as well as the practice of computational biology and bioinformatics, through graduate fellowships and undergraduate research experiences. Establish interdisciplinary graduate postdoctoral fellowships in plant genomics with an option for international collaborations. This could be modeled on the success of the Arabidopsis 2010 Project: International Research Experience for Graduate Students and Postdoctoral Fellows that supports exchanges between U.S. and German laboratories. Stimulate undergraduate student interest in plant genomics, especially among populations of students who might be less aware of research career opportunities, through expanded research opportunities with trained mentors and through integrated inquiry-based activities in undergraduate and precollege courses. Develop well-designed educational activities that draw on the latest learning theory research and devise mechanisms for educators to share these initiatives, by creating a new class of PIs dedicated to education and by funding professional education managers to coordinate outreach activities. Expand the Plant Genome Research Outreach Portal (PGROP) to include a comprehensive collection of existing outreach programs, with evaluative information, and links to assessment tools.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology BOX 3-3 Ethical, Legal, and Social Issues Associated with Plant Genomics Biological and social benefits and risks of plant modifications derived from genomics that use recombinant DNA, such as genetic engineering or GMO approaches. Sustainablity and biodiversity in the broad biological and social senses, and the extent to which genomics-aided breeding can aggravate or mitigate these concerns. The appropriate role for formal social controls on intellectual property protection and regulation as related to income distribution, business development, and social cost and benefit tradeoffs. The increasing controls over international germplasm movement and attendant concerns about biopiracy. These regulations may seriously hinder genomics based plant breeding and research progress in both the developed and developing worlds. The extent and control of unintensional contamination of germplasm. Critical translattion research can be hampered—against a backdrop of stringent social intolerance—by dispersal and adventitious presence of foreign genes due to inadvertent pollen, seed, and vegetative dispersal from exotic genotypes, species, and transgenes. Public education and outreach about the goals and rationale for genomics and related biotechnology research. Broad social approval of plant genomics deployment will be dependent on judgments of social and personal benefit in comparison to risk. (Hossain et al. 2003). NPGI PIs should try to forge connections with engineers and computational scientists, with the goal of attracting students in these fields to plant genomics at the graduate level. NPGI PIs should encourage changes in the undergraduate curriculum at their own institutions and participate in the reformation. PIs should also be encouraged to participate in similar reforms in their institutional Ph.D. programs in genomics so that two courses in statistics and competence in a modern scripting language become standard requirements for advanced degrees. Establish mechanisms to engage sustainable, organic, and small-scale farmers in identification of specific traits for which applications of genomic tools could lead to usable varieties with enhanced performance characteristics. 10-year goal Expand training in ethical, legal, and social issues pertaining to plant genomics for K-12 and undergraduate students and teachers, and for NPGI predoctoral and postdoctoral stipend recipients.
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Achievements of the National Plant Genome Initiative and New Horizons in Plant Biology 20-year achievements Integration of research and education in plant genomics will rival that of biomedical genomics in creativity, in public profile, and in the ability to attract new students. The plant genomics community will provide leadership in contributions toward public outreach on ELSI issues, including engagement in development of science-based regulatory policies at national and international levels, by NPGI-funded programs and NPGI-trained students and postdoctoral associates.