Grand Challenge Project Proposal for the iPlant Collaborative Fundamental Understanding of Photosynthesis through Integration of Complex Molecular Data and Modeling Tools Principal Leaders Thomas Brutnell (Contact Person) Richard Bruskiewich Xinguang Zhu Christopher Myers Martin Gent Pankaj Jaiswal Shaoying Kathy Lu Title, Affiliation & Contact Details Expertise/Role Associate Scientist, Boyce Thompson Institute, Cornell University, Ithaca, NY; Ph: +1 (607) 254-8656; Email: [email protected] Senior Scientist, Computational & Systems Biology, Crop Research Informatics Laboratory and Applied Photosynthesis and Systems Modeling Laboratory, International Rice Research Institute (IRRI; www.irri.org) Ph: +1 (650) 833-6620 Email: [email protected] Group leader, Plant systems biology, photosynthesis research, CAS - MPG Partner Institute of Computational Biology (PICB; www.picb.ac.cn), SIBS, Shanghai, China Ph: +86 (21) 549-204-58 Email: [email protected] Plant molecular biology/genetics. Source of primary high-throughput leaf transcriptome and metabolome data sets. Outreach efforts. Genomics, bioinformatics, computational & systems biology / Development of infrastructure for functional genomics data analysis & integration; software engineering for crop information systems; source of rice and sorghum mutant data sets, with photosynthesis measurements. Research Scientist, Institute for Genomic Biology, National Center for Supercomputing Applications, University of Illinois at Urbana Champaign, IL, 61801 Email: [email protected] Senior Research Associate, Computational Biology Service Unit, Life Sciences Core Laboratories Center, Cornell University, Ithaca, NY Ph: +1 (607) 255-5894 Email: [email protected] Agricultural Scientist, Connecticut Agricultural Experiment Station, New Haven, CT Ph: +1 (203) 974 8489 Email: [email protected] Assistant Professor, Department of Botany and Plant Pathology; Center for Genome Research and Biocomputing, Oregon State University, Corvallis, OR Ph: +1 (541) 737-8471; Email: [email protected] Research Scientist, Department of Bioengineering, University of Illinois at Urbana Champaign, 61801 Email: [email protected] Computational & systems biology / Development of modeling framework for photosynthesis; Source of some high throughput photosynthesis measurements Computational physics & systems biology / Development of modeling framework for photosynthesis and linking to infrastructure for data analysis of high throughput data sets Whole plant physiology / Data and models for leaf and canopy photosynthesis; transport of water and metabolites, composition of plants as affected by light and temperature Comparative plant genomics, genome annotation, genome and pathway databases / Development of infrastructure for high throughput leaf sequence, transcriptome, proteome and metabolome data sets Applied mathematics & high performance computing / Development of 3 dimensional simulation package of reaction diffusion system Project Summary The success of the green revolution in the 1960s and 1970s led to dramatic increases in world food production. However, to ensure that agricultural systems can meet future production needs it is imperative to overcome physiological barriers to crop yield and improve the resiliency of crops to adverse conditions such as climate change. The most obvious physiological limitation to crop yield is imposed by the fundamental process by which green plants harvest sunlight to capture carbon dioxide in the atmosphere and bind it into sugar, which the plant then uses as a substrate for further synthesis of its biomass, the process called “photosynthesis”. Project Goals and Objectives The proposed project will have the goal of providing innovative cyberinfrastructure for scientific research into the process of photosynthesis, thus greatly advancing our capacity to solve two global challenges in plant biology: a) Enhancing photosynthetic efficiency in crop plants of agronomic importance; and b) Identifying a strategy to convert agronomically important plants, such as rice and wheat, to use the more efficient variant of photosynthesis which is found in species like maize and sorghum. To achieve the above scientific objectives, we envision the following five key project deliverables: 1. A community portal for photosynthesis research 2. A public data repository for photosynthesis research. 3. A knowledge discovery environment for photosynthesis systems biology. 4. A simulation environment for systems modeling of photosynthesis. 5. An education, outreach and training portal for photosynthesis science. Outreach and Training for the Plant Science Community The outreach component of this project will strive to develop capacity for computational science in photosynthesis research within plant scientific community with a number of activities: • • • Develop training materials and host training workshops (in the USA) for photosynthesis modeling. Incorporate international exchanges (targeting photosynthesis research scientists, in particular, from developing countries) into GC project activities, with photosynthesis research team members such as photosynthesis modeling experts, graduate students and postdoctoral scientists from within the US and abroad. Develop (US) national curriculum resources (high school and undergraduate level) for training in plant cyberinfrastructure relating to computational systems biology modeling and photosynthesis research. The project will also broaden public understanding of science through the following activities: • • • Education and information specifically targeting photosynthesis: developed and delivered for many cognitive levels, such as primary, secondary, and post-secondary schools, for general information by an educated lay public (e.g. wiki content); and as a tool for policy makers. Development of a simplified simulator of leaf and/or whole plant photosynthesis, as a means for science education. “Summer schools” in plant photosynthesis modeling for senior high school and undergraduate students to participate in some of the laboratories developing or applying the cyberinfrastructure from this project. Introduction: Grand Challenge of Photosynthesis The success of the green revolution in the 1960s and 1970s led to dramatic increases in world food production. However, with the exception of maize, production increases have been extremely limited in cereal crops over the past ten years. Increasing world population, global climate change and increasing energy costs are together creating a crisis in the global food supply. Recent estimates are that world wheat stockpiles are at a 30 year low [1] and in April 2008, rumors of a rice shortage resulted in riots in 30 countries throughout the world. This tenuous situation has been brought about in large part by global population growth that is expected to exceed 7 billion within the next ten years. The transformation of the large Chinese and Indian economies resulted in never-before-seen demands on grain supplies accompanying growth of the middle class. Indeed, despite the recent collapse of global financial markets, commodity prices for rice, wheat and soy remain at near historic highs [2, 3]. To ensure that agricultural systems can meet future production needs it is imperative to overcome physiological barriers to crop yield and improve the resiliency of crops to adverse conditions such as climate change [4]. Yield in crop plants may be generally modeled by the equation [5]: Y = H ∫ ε Iint(t) dt where Y H ε Iint yield harvest index radiation use efficiency (a function of development or time) intercepted photosynthetic active radiation (PAR) and the integration of the function is over the time from germination to harvest. Intercepted PAR is primarily a function of climate and weather during growth, but is also influenced by plant architecture (e.g. erectness of leaves). In many elite crops, morphological traits relative to efficient PAR interception have been relatively well optimized. The timing of development from germination to senescence has some genetic diversity, but in general, is not a convenient variable to be maximized: farmers generally desire shorter rather than longer growing seasons, to reduce risk of crop loss. Although significant efforts have been made in breeding for superior yield components, harvest index is relatively invariant within species. Indeed, Figure 1. Photosynthetic Energy Efficiency recent observations suggest that crops like rice are source not sink limited [6]. This analysis leads to the conclusion that fundamental improvements to radiation use efficiency, that is, enhanced efficiency of photosynthetic capture of CO2 into sugar, is likely the ultimate target for manipulation to increase yield [5]. One of the major barriers to yield in many crop plants is the relative inefficiency of solar energymediated capture of CO2 into sugar [5, 7, 8]. Theoretical analysis suggested that the maximal radiation use efficiency, εc, for C3 and C4 plants are 4.6% and 6%, respectively; however, actual efficiency barely exceeds 0.5% in the field over an entire growing season (Figure 1; [9]. Current models of photosynthesis suggest several avenues of biological engineering to increase photosynthesis energy conversion efficiency (Table 1). A full understanding of photosynthesis would allow improvement of existing photosynthetic processes in crops, and to possibly enable genetic engineering of C3-type photosynthetic systems toward the more efficient C4-type photosynthesis. This will require the efficient integration and sensible interpretation of voluminous and complex data and models, spanning a range from genomic data through crop eco-physiological responses. Now is the time to achieve such an understanding through powerful comparative genomics approaches. Experimental approaches are rapidly evolving for the functional 1 characterization of completed genomes, such as the model dicot, Arabidopsis thaliana, and model monocot, Oryza sativa. These data are being supplemented by significantly completed genome sequences for at least two major of C4-type photosynthetic species, Sorghum bicolor [10] and Zea mays (maize). Table 1 – Potential Alterations to Crop Photosynthesis to Enhance Energy Conversion Efficiency Projected Range of % increase in εc Speculated Time Horizon (yr) Citation Improved canopy architecture 0 - 40% 0-10 [11] Rubisco with decreased oxygenase activity 5 - 60% ? [12] Increased rate of recovery from photoprotection of photosynthesis 6 - 40% 5 [13] Introduction of higher catalytic rate foreign forms of Rubisco 17 - 30% 5-10 [12] Altered allocation of resources within photosynthetic apparatus 0 - 60% 0-5 [14] 25% - 50% 15-30 [9] Alteration C4 photosynthesis engineered into C3 crops GC Project Goal To develop a novel discovery environment (“DE”) of computational tools to assist scientific research directed toward the improvement of photosynthesis to enhance crop yields. The above Grand Challenge (“GC”) project goal will support two major scientific objectives: 1. To develop photosynthesis process models and simulations at multiple scales of spatial and temporal resolution and establish their underlying genotype-to-phenotype linkages, in order to identify opportunities for genetic manipulation or breeding to enhance energy conversion efficiency in existing C3 and C4 systems. 2. To identify strategies to convert the photosynthetic system of C3 crops into the more efficient C4 type photosynthetic system. These scientific objectives require the systematic development and application of a sophisticated plant photosynthesis research cyberinfrastructure (“CI”) that would allow multidisciplinary teams of plant scientists to collaborate through models of the process and differentiation of photosynthesis, in order to gain a quantitative understanding of the system efficiency and its formation. GC Project Objectives To achieve the above scientific objectives, the project will develop the following five CI resources: 1. A community portal for photosynthesis research. 2. A public data repository for photosynthesis research. 3. A knowledge discovery environment for photosynthesis systems biology. 4. A simulation environment for systems modeling of photosynthesis. 5. An education, outreach and training portal for photosynthesis science. Scientific Approach Enhancement of Existing Photosynthetic Processes Models of photosynthesis have proven useful to predict photosynthetic performance and provide opportunities for engineering higher efficiency. For example, detailed simulation model of carbon metabolism suggested an opportunity to increase photosynthesis output by increased expression of some 2 genes, such as sucrose-bis-phosphatase (SBPase) (Figure 2a). These predictions were realized in tobacco plants overexpressing SBPase (Figure 2b). Figure 2. a) (Left) Model of Carbon Metabolism [14]. The red box denotes a reaction catalyzed by SBPase for which model simulations indicated increased activity could increase the amount of carbon capture. b) (Below) Raines and colleagues [15] transformed tobacco with an SBPase enzyme. High expression of the transgenic enzyme increased biomass growth relative to a control plant. Critical milestones to the achievement of the first objective of enhancing photosynthetic systems are: 1. Enumeration and quantification of the contribution of different factors (biochemical, biophysical or anatomical) that control the efficiency of photosynthetic energy conversion. 2. Determination of how the major developmental events in photosynthesis are coordinated in the differentiation of leaf tissues. 3. Identification of the regulation of metabolite levels in photosynthetic pathways, both during development and differentiation, and also to maintain homeostasis in mature tissues. 4. Identification of the genotype-phenotype linkages underlying regulatory and metabolic pathways of photosynthesis, and their response to environmental stress related to water and temperature. 5. Identification of genetic options to incrementally improve the energy conversion efficiency of photosynthesis and robustness of photosynthesis under stress. To achieve these goals we envision the following critical modeling needs: 1. Establish parameterized reference models of photosynthesis: a. Develop a baseline photosynthesis model at the cellular level, using existing expertise and knowledge at the levels of genome, metabolism, and cell anatomy. b. Estimate model parameters for selected plant species based on photosynthetic measurements of these species. c. Conduct ab initio parametric sensitivity analysis of integrated model to identify parameters that have biggest impact on photosynthetic performance 2. Use structural and functional genomic approaches - e.g. mutant analysis and available functional annotation in model plants like Arabidopsis and rice to dissect the genetic control (“candidate genes” and regulatory elements) of leaf anatomy and photosynthetic biochemistry. 3 3. Integrate photosynthesis performance measurements, and apply high-throughput parameter estimation, to additional selected collections of plant germplasm; domesticated and wild plant 1 species, and well-characterized (i.e. QTL or genotyped) core collections of plant germplasm . Measure photosynthesis for such germplasm under various stress treatments. Molecular variation (“alleles”) in candidate photosynthesis genes and their regulatory elements should be associated with model parameters. 4. Confirm parametric sensitivity analysis of integrated models using results from the above analysis across diverse germplasm, including model response under stress. Assess candidate genes and alleles for impact on photosynthetic performance of measured plants. Through the development of these models, it will be possible to identified genes and alleles conferring superior photosynthetic performance. Promising alleles could then be incorporated into breeding programs for further testing and possible deployment and to the specific engineering of proteins and pathways for crop improvement. Conversion of C3-type to C4-type Photosynthesis In C3 plants carbon entering a cell is fixed by the chloroplast localized enzyme ribulose-1,5bisphosphate carboxylase oxygenase (Rubisco) into two three-carbon sugars. However, oxygen competes with CO2 for the active site of Rubisco and when conditions are unfavorable for gas exchange with the ambient air (i.e. hot, arid environments) stomates close, resulting in an internal O2 increase while CO2 levels drop. The result is a loss of photosynthetic capacity in the form of photorespiration. As temperatures increase, the capacity for Rubisco to interact with O2 increases and a dramatic reduction is exhibited in CO2 fixation and photosynthetic efficiency. Calculations show that C3 plants can lose nearly o 30% of potential carbon fixation due to photorespiration at temperatures higher than 30 C [16]. In the C4 pathway, atmospheric CO2 is initially fixed into C4 acids via phosphoenolpyruvate carboxylase – PEPC, an enzyme that is insensitive to O2. Later, CO2 is released from the C4 acids for fixation by Rubisco. The two stages are spatially separated in morphologically distinct photosynthetic cells, mesophyll cells and bundle sheath cells. The resulting overall leaf architecture is called “Kranz anatomy”. The active transport of C4 metabolites between cells and barriers to diffusion of CO2 are critical to C4 photosynthesis. In C4 grasses such as maize and some C4 dicots, enlarged bundle sheath (BS) cells surround the veins (V) and the BS cells are then surrounded by mesophyll (M) cells. M cell chloroplasts support the capture of CO2 by PEPC, whereas BS chloroplasts support fixation of CO2 by Rubisco. This separation allows a metabolic “CO2 pump” to develop a high concentration of CO2 in the vicinity of Rubisco. The buildup of CO2 by this process requires extra energy, but the overall reduction in energy loss is compensated by the fact that photorespiration is greatly reduced in C4 plants [17, 18]. Importantly, nearly all of the world’s most productive food, feed and bioenergy crops - including maize, sorghum, sugarcane, Miscanthus and switchgrass – utilize C4 photosynthetic systems. The physiological and morphological adaptations that accompany C4 photosynthesis also improves water use and nitrogen efficiencies relative to C3 plants [19]. In nature, C4 appears to have evolved out of C3 lineages more than 50 times in a wide range of flowering plants and over 18 times in the grasses [20]. Evidence indicates that there is one consistent evolutionary pathway from C3 to C4 photosynthesis, based on genera that have C3 species, C4 species, and species with intermediate traits [18]. The frequency and apparent ease with which C4 evolves suggests plasticity inherent to the C4 syndrome. It is important to point out that key enzymes of the C4 pathway are present in C3 plants, but their activities and expression patterns are different [21]. Perhaps, a change in anatomy leads to changes in biochemistry or vice versa. Identifying such mutations would provide alternative ways to C4 rice— duplicating the evolutionary event. However, knowledge about the evolution and developmental genetics of C4 photosynthesis is not yet sufficient to achieve this feat artificially, and this task remains a GC of plant science. 1 For example, the OryzaSNP collection of genotyped rice germplasm. 4 Little is known about communication between M and BS cells in C3 or C4 plants. There are two general hypotheses: either a signal emanates from veins and is perceived differently in cells closer to the vein, or a signal is mediated by physical contact between BS and M cell walls [22]. To investigate the mechanisms underlying C4 development several groups are conducting transcriptome, proteome, metabolome and phenome surveys of maize, rice and sorghum (e.g. these and related studies are now generating extensive data sets that can be mined to identify control points in photosynthetic differentiation). However, the CI to fully exploit these data sets is currently not available. To convert C3 to C4 photosynthesis, scientists will need to identify the genes and networks that control the following: 1. Cell number between veins and the size and number of bundle sheath cells. 2. Chloroplast number, differentiation and distribution in mesophyll and bundle sheath cells. 3. The different metabolism in mesophyll and bundle sheath cells. 4. Subcellular features such as plasmodesmata density and structure, chloroplast membrane transport systems and CO2 permeability that mediate the flux of metabolites between the mesophyll and bundle sheath cells. These research questions will require computational and systems biology methodology to synthesize a large body of functional genomics data relating to C4 photosynthetic processes. Assuming that a baseline C4 photosynthesis model is specified as a part of objective 1 above, then a plausible research strategy to C4 photosynthesis will require the following: 1. Integrate, visualize and interpret comparative structural and functional genomics data to dissect C4 Kranz anatomy and biochemical pathways. a. Compare -omics datasets of “C3 reverting” mutants of C4 plants with wild-type b. Compare coding and regulatory genomic sequences in C3 and C4 species c. Compare transcriptome, proteome, metabolome and phenome expression across developmental stages and tissue (cell) types in reference genotypes in C3 and C4 species. 2. Use the integrated photosynthetic model to identify key genetic targets for modification, then design and apply a suitable strategy for engineering of C4 photosynthesis into C3 crops. The challenge of converting C3 -type photosynthesis into the more metabolically efficient C4 type has been taken up by the international scientific community (http://seeds.irri.org/C4rice). Through Gates-Foundation funding, an international consortium will generate extensive data sets from –omics level biological experiments. The main thrust of the funded research initially focuses on the elucidation of Kranz anatomy underlying multi-cellular C4 pathway and engineering the C4 carbon cycle into rice plants. Importantly, the long-term success of this project will depend, in large part, on defining key regulatory points for manipulation and on a sophisticated analysis of molecular data sets to fill large gaps in knowledge of this process. This demands a CI environment that is envisioned but is only partially resourced within the Gates-funded consortium. Current Barriers in Photosynthesis Research Substantial barriers prevent an integrated discovery environment for photosynthesis research. One major challenge is to develop a new modeling framework that includes a greater variety of processes than has been developed to date. First, most existing cellular models generally only describe a single cell. The C4 photosynthetic process requires two kinds of cells work together, so the model must handle the multi-cellular nature of this system. In both C3 and C4 leaves, a gradient of light and CO2 across the leaf requires integration of leaf tissue geometry and simulation of photosynthetic processes across multiple layers of cells. Second, the model must handle multiple types of processes simultaneously. Genetic control, biochemical metabolism, and trans-membrane transport and diffusion all play a role in operation of the C4 photosynthetic system. We need to maximize ease-of-use of this modeling framework to enhance the willingness of plant biologists to use modeling as a tool in their research. Most molecular biologists cannot access and use quantitative modeling tools. There are several reasons for this: 5 • Quantitative models are usually developed by scientists with a mathematics, physics, and computational background. Hence, experimentalists find it difficult to understand and use them. • Models often lack methods to estimate the robustness and sensitivity of results to input errors. • Parameter estimation is difficult. Data sets are diverse, including many species and environments, and the data are stored with multiple formats and diverse semantics. • Most plant biologists are reductionists, not accustomed to systems-oriented thinking. • Genetic regulation of anatomical parameters has not yet been related to photosynthesis. Now is the time to assemble these different components in a quantitative model to analyze system performance and the interaction between different components of the whole system. It is also critical to develop a curriculum to train scientists to conduct integrative photosynthesis research based on this cyber-infrastructure. Scope of the Grand Challenge Project The initial short-to-medium term scope of our project is limited to the development of CI to support generic, parameterized, leaf-centric models focused on processes related to photosynthesis, for a selected set of plant species. In future years the CI framework should ideally be extended to canopy level analyses. Whole plant level processes such as the interaction of stem, root, and flowers - and extension of models to other crops are beyond the scope of this proposal. Discovery Environment (DE) for Photosynthesis Research As indicated above, we envision five key project development objectives that characterize a Discovery Environment (DE) for photosynthesis research: 1. To establish a community portal for photosynthesis research. 2. To establish a public data repository for photosynthesis research. 3. To build a knowledge discovery environment for photosynthesis systems biology. 4. To develop a simulation environment for systems modeling of photosynthesis. 5. To develop for education, outreach and training resources relating to photosynthesis science. Web Portal for Photosynthesis Research Although some early efforts toward this goal exist in the scientific community, there is not yet a comprehensive web-based community portal for photosynthesis research. The lack of such a web portal for plant biologists in general and the global photosynthesis research community in particular, may be a hindrance to rapid advances in the field. This GC project therefore proposes the creation of such a web portal as a specific output deliverable on the project. The proposed web portal will take advantage of socalled Web 2.0 collaborative technology to assist community wide coordination of photosynthesis research activities. First, the portal will provide the primary interface to a comprehensive index and repository of cross-referenced public molecular and physiological data for photosynthesis research (project objective 2). Second, the portal will be the public face to a workbench of web-based tools for data analysis and integration – the Knowledge Discovery Environment for Photosynthesis Systems Biology (project objective 3) and provide access to a Simulation Environment for Photosynthesis Systems (project objective 4). Third, portal will be the primary vehicle for dissemination of project educational outreach and training resources to the community (project objective 5). Data Repository for Photosynthesis Research Primary data, derived information (i.e. structured, cross-referenced, analyzed data sets) and scientific knowledge (literature) relevant to photosynthesis research are not currently consolidated and accessible from any one single site globally. The lack of such a unified repository hampers efficient data mining and achievement of an integrated understanding of photosynthesis. Computational experiments such as model building, parameter estimation and simulation cannot be efficiently undertaken. Thus, a key objective of this GC is to develop a comprehensive data repository for photosynthesis research. 6 A wide variety of biological data sets will be consolidated into the data repository and an ontology framework for semantic integration specified. These will include key discrete –omics data and also, continuous physiological response data. The repository will also index publicly available photosynthesis systems models (see Appendix A1, Objective 2). An enumeration of public data sets potentially available for the GC is provided in Appendix C. The key technical activities with respect to the photosynthesis data repository would include: 1. 2. 3. 4. Enabling continuous discovery of available data specific to our scientific queries Promoting ease of access and use of this discovered data Compilation of associated annotation and meta-data (especially, semantic linkages). Enabling facilities for comparative scientific analysis and integration of data. Tools to determine the quality of source data will be important. For example, availability of accurate gene structures for rice/sorghum/maize genes will be critical to the task of clarifying gene function, C4 versus C3 genetic variation, and for the identification of potential cis regulatory motifs in promoters, enhancers, chromatin, etc. upstream of genes. The data management framework should also allow distributed community curation of data to increase accuracy of gene structural predictions and functional annotation. Knowledge Discovery Environment for Photosynthesis Systems Biology These data sets may be cross-referenced using CI approaches to facilitate a systems biology understanding of photosynthesis. The above criteria suggest that the DE for this GC would require a sophisticated software framework for automated ad hoc queries of internet distributed data sources, in order to alleviate the tedium of manual “hunter-gatherer” compilation. A number of available approaches to achieve this objective are under consideration by iPlant (e.g. ontology, web services, semantic web, etc. see [23, 24]). Such a semi-automated framework must provide a solid “audit trail” of evidence relating to the criteria of where, how and why the data or information was collected. This GC project therefore needs the following bioinformatics tools: a. A comprehensive semantic and software integration framework (“middleware”) to cross-link diverse local and remote data sources, for efficient access by diverse CI analytical applications. b. Text mining tools to mine public scientific literature for knowledge related to photosynthesis and related plant metabolic processes. The results of such text mining can be used to populate a comprehensive knowledge-base for photosynthesis. c. A general data-mining tool to discover, browse and synthesize available photosynthesis data sets. d. General for sequence analysis of diverse coding and regulatory sequences related to photosynthesis. e. Facilities to undertake genome (sequence level) and functional (expression level) alignments between diverse C3 and C4 sequenced genomes such as Arabidopsis thaliana, Oryza sativa, Sorghum bicolor, Zea mays, Panicum virgatum (switchgrass) to identify and transfer molecular biology knowledge of model species (e.g. Arabidopsis and rice) to non-model species and also, to facilitate recognition of genes related to both C3 and C4 photosynthesis. In particular, such a facility will help identify similarities and differences in gene and associated regulatory sequences (promoters). f. Comparative tools that access to available databases cataloging molecular sequence diversity of genes within C3 and C4 crop germplasm, to identify molecular variants in the coding and regulatory regions of photosynthetic genes for targeted conventional “marker assisted” breeding to improve crop photosynthetic productivity. g. Computational tools to identify metabolic pathways, genetic regulatory networks, protein-protein interactions, and signal transduction pathways implied by high throughput data and comparative genomic analyses. h. Facilities to combine time-series data of metabolites with gene and protein expression data. One possible approach would combine the ordinary differential equation modeling approach with a statistical inference approach. 7 Various levels of data need to be cross-linked to one another using widely understood basic biological relationships. For example, genome sequences should be connected to their associated transcriptome. Transcripts should then be tied to associated RNA or peptide products (i.e. codons should to specific amino acid residues, and possibly, to their inferred impact on protein structure and function.). Known functional information about those gene products, including participation in pathways, protein complexes, processes, cellular structures and regulatory networks, should be readily available. Particular emphasis needs to be placed on DE tools for comparative biology, to elucidate structure/function similarities and differences across species like C3 rice or wheat, against C4 organisms like sorghum or maize. Given the continued public characterization of such diverse genomes, comparative genome alignments of such species will become an increasingly more powerful and essential tool to understand the photosynthetic differences between them. The DE should also provide a simple and intuitive navigation interface to a complex and rich set of possible workflows and operational modes. The common data analysis workflows will form a toolkit that can be easily used by users to analyze genomic data. Perhaps each such workflow or mode may be represented as a graphical “view” of one underlying common conceptual framework integrating the available data. The design of such views should apply “best practices” for graphical user interface design. They would provide the ability to hide/show or filter information selectively, to discriminate different data points using differential symbolic, color and textual clues (including dynamic clues like popup “tool tips”). At any point, the user should be able to explore related data, or review the audit trail of available evidence underlying the specific data displayed on the screen. The DE should allow researchers to collect harvest data into a session-persistent private local, semantically well structured project databases, seamlessly linked to public data sources. Researchers should be able to locally compile (“shopping cart” style) and visualize collections of data based on the research-question driven queries. These data collections may be used in formalized bioinformatics workflows (e.g. specified using tools like Taverna; http://taverna.sourceforge.net/), or as a source of empirical parameters for simulation models. The DE should provide statistical tools to integrate different kinds of genomic information for new knowledge generation. The DE should provide facilities for the generation of annotated graphics derived from the various visual representations of available data and models. For example, the generation of annotated two and three-dimensional diagrams of leaves, tissues, cells, organelles, molecular pathways and networks (regulatory, metabolic, etc.) and gene structures should be possible. The generation of graphical plots of variables over a time course should be possible for various model simulations. Formatted tables of qualitative and quantitative information from the system, exportable to worksheet (e.g. Excel) tools should also be possible. Linkage of all such “views” to underlying data should be dynamic so as to reflect the latest available data. The initial data set that will be used for the model building will be published photosynthesis literature and associated data sets, crop and leaf photosynthetic physiology datasets, data set for general model plant species (Arabidopsis, rice, maize), leaf level expression, protein, metabolic dataset for these model species (in particular Arabidopsis and rice), the "rice atlas" data at Yale University; whole genome sequence maps and annotation for Arabidopsis, rice, maize. Some unpublished data that will be available to be used in this project include photosynthesis data IRRI wild rice measurements (CO2 compensation points, vein spacing). In the near future, the following data set will be obtained : NSFfunded rice/maize/sorghum leaf transcript, protein, and metabolic data available from Yale and Cornell University; the leaf anatomy, biochemistry, metabolite flux, and physiology data from Shanghai Institute of Biological Sciences. Mutant data, expression and transgene molecular data for C4 and C3 plants from IRRI projects funded by the Gates foundation. Appendix C provides a more extensive summary of several available or pending data sets. Simulation Environment for Systems Modeling Of Photosynthesis The key, long-range output of this GC for photosynthesis research will be the development of a sophisticated new simulation environment for photosynthesis research. The technical purpose of this simulation environment will be two-fold: 8 1. To specify and simulate three-dimensional (geometric, anatomical) models of photosynthesis metabolism and differentiation 2. To identify and predict genes that could be targets for crop improvement Given the complexity of the task, the development of software supporting this output will be spread over a longer period of time than the previously described project outputs. Likely, this task will be subdivided into multiple stages: • Stage 1: Integration of currently available kinetic/metabolism models and auxiliary algorithms into a common framework and their generalization to incorporate emerging molecular data sets • Stage 2: Development of reference models (3D models of single cell; 3D model of multi-cellular leaf photosynthesis ) using existing packages • Stage 3: Develop a generic simulation environment for modeling 3 dimensional reaction diffusion system using existing algorithms to enable user-defined photosynthesis model to be easily built Broadly speaking, stage 1 is thought to be tractable within a 2-year project period; stage 2 may extend to 5 years; stage 3 will likely be a significant research and development exercise over 10 years. Development of Stage 3 will build on the experiences gained during stage 1, 2. A natural conceptual framework for a DE for photosynthesis research would be a structured spatial-temporal visualization and modeling of leaf morphology. That is, a DE could provide spatial integration and visualization of data centered on the morphological models of (monocot) leaf anatomy and physiology. This is needed at a variety of interrelated levels: from whole plant level, through whole leaf, through leaf organ/tissue level (MC, BSC, epidermal cells, stomata, leaf veins, etc. inclusive of cell-cell junctions), through whole cells, down to subcellular organelles (cell walls, chloroplasts, mitochondria, cytosol, nucleus), down to the genomic level (chromatin, nucleoli, etc.). The DE should be a “plug and play” toolkit permitting public and semi-public sharing of “Lego Blocks” for building such morphological models. The design of such a toolkit might borrow ideas from analogous “computer assisted” parametric geometry-driven 3-dimensional modeling environments, in fields such as architecture (e.g. Autodesk Revit Architectural software, http://www.autodesk.com/revit) and engineering design. On the molecular level, the framework should provide analysis and visualization tools to represent models of gene and protein function, and should provide for visualization of available genome annotation and experimental data, such as expression, proteomic, and metabolic data. It should allow visualization of protein complexes important to photosynthesis. The geometric models should allow representation of diverse phenotypic variants, for example, disrupted leaf tissue anatomy observed in mutagenized plants (e.g. leaf structures from C3 reverting mutants). In addition to spatial detail, the toolkit should also provide time-dependent kinetic modeling of several kinds. First, the framework should support modeling the spatial-temporal trajectories of leaf development, or the leaf morphogenesis events. That is, researchers should be able to simulate the sequential series of developmental steps to the mature leaf stage. Such developmental modeling should include the gross processes of leaf organization, such as the development of asymmetrical chloroplast localization in C4 leaves. The framework should also provide for a specified proliferation and differentiation in time and space for chloroplasts and mitochondria as well as cellular localization, and changes in membrane and cell wall function and transport (Figure 3). This kinetic modeling may have to scale from nanoseconds through hours to provide a quantitative simulation of the ordered progression of physiological, cellular, metabolic and genetic biological processes during development. This would include processes from the – sub-cellular or organelle level, through multi-cellular (leaf) tissue level. The modeling environment would allow users to define the reaction mechanisms and corresponding physical and chemical constants, with automatic generation of the resulting systems of differential equations. A series of metabolic reaction sequences focusing on the key processes related to C4 photosynthesis will be provided as a pilot model for the platform. Results of such kinetic models should be displayed in three dimensions super-positioned on a graphical representation of the anatomy of 9 the leaf. The framework will simulate not only the metabolic flux, but also the genetic regulation by both the organelle and nuclear genomes. The DE needs to simulate multiple phenomena in a continuous or discrete/stochastic fashion. This framework will not only incorporate chemical reactions and gene expression events; it will incorporate the physical processes of gas and metabolite diffusion, energy exchange at the leaf surface etc. All these processes occur within a defined 3-dimensional leaf anatomy. Therefore, the framework must consider spatial dimensions of these various processes. Quantitative physical simulations should be coupled to biological development phenomena such as cellular proliferation, differentiation and cellcell interactions, including especially cell membrane and wall transport and function. Figure 3. Geometrical spatial integration and visualization of data within morphological models of leaf anatomy and physiology, at a variety of interrelated levels: from whole plant level, through whole leaf, through leaf organ/tissue level (i.e. MC, BSC, epidermal cells, stomata, leaf veins, etc. inclusive of cell-cell junctions), through whole cells, down to subcellular organelles (cell walls, chloroplasts, mitochondria, cytosol, nucleus), down to the genomic level (e.g. gene structure and allelic variation) The model outputs need to be linked to laboratory results or quantitative physiological indices relevant to C4 photosynthesis, such as quantity and location of transporters across cell and organelle membranes; CO2 compensation point; CO2 permeability across membranes; C4 enzyme kinetics; leaf gas exchange parameters etc. These quantitative indices can be obtained from experiments. They can be used to validate, invalidate and improve the predictive models. Once this model framework is developed, it will allow testing “what if” hypotheses. For example, it can be used in sensitivity analyses to study the effects of changing any underlying component in the system, hence, providing an in silico tool for predictive modeling of the genetic basis for C4 characteristics. To be more specific, there is a genetic basis for each of the determinants of either kinetic properties (enzyme kinetics, protein synthesis and degradation rates, mRNA synthesis and degradation rate etc) or structural properties (anatomical, metabolic network structure, genetic regulatory network etc). The effect of altering the genes for any determinant could be modeled in terms of its impact on C4 photosynthesis. Second, the DE needs to combine mechanistic models with statistical models. Statistical models include network connectivity models that describe the relationship between different reactions in the metabolic network, or the characteristics of cellular morphology at different locations in leaf tissue. The relationships are usually statistically inferred from high throughput genomic level data. On the other hand, mechanistic models are based on specific hypotheses concerning the biochemistry of metabolic steps. These two types of models have been developed independent of each other and correspondingly are 10 separated from each other, although research into connecting mechanistic models at one scale to statistical models at other scales may ultimately be required. Third, the DE should enable comparison of structure and function relationships between diverse C3 and C4 species, between C4 species, and for different tissues of a given plant, or same tissue under different conditions. The facility for comparisons should be available both on the level of genomic sequences – gene structures and regulatory regions like promoters – and at higher levels of biology – transcript, protein and metabolic and phenotypic (e.g. mutant plant) profiles. These analyses will help identify potential genes responsible for the generation of C4 characteristics. Large biological data sets are available within the C4 research community for such analyses (Appendix C). Fourth, a sensible indexing of candidate gene networks should integrate all available gene expression data; transcriptome, proteome, metabolome and phenome. Such genetic networks may themselves be modeled visually as connected graphs (nodes plus edges) annotated with proper evidence, and with qualitative and quantitative indications of the nature of the identified genetic interactions. The metabolic reaction networks within each cell type should be provided in a similar framework. This network will be updated dynamically using the most recent data available. The confidence level of each edge in this network will be explicitly given. A number of auxiliary tools need to be developed to enable effective use of the resulting CI. 1. Computer programming standards to enable plug-and-play style quantitative model building. 2. Optimization routines to identify the best model parameters to fit to given data sets including the goodness of fit to multiple sources of photosynthesis measurements. 3. Facility to use time series metabolic, transcript profiling, and proteomics data for parameter estimation in mechanistic models. This capacity is critical because we are still quite limited in estimation of the kinetic parameters used in mechanistic models. 4. Graphical interface to support construction of comprehensive 3-dimensional models of multi-cellular C3 or C4 photosynthetic systems, with linkage to experimental data sets. 5. Simulation (“evolutionary algorithm”) and sensitivity analysis tools to identify and quantify key parameters and components. Identify parameter spaces that are stable, and regions of parameter spaces that are highly sensitive to perturbations. This platform will provide synthetic biology tools to identify the optimal sequential engineering changes needed to gain desired traits, such as engineering C4 photosynthetic properties from C3 photosynthesis. Considering that most of the complex traits in plants are evolved via multiple steps, the platform will enable evaluation of the fitness and difficulty of each step in genetic engineering, correspondingly suggesting the most feasible option. Several algorithms applicable to a plug-and-play model need to be developed: 1. Integration of processes occurring at drastically different time and spatial scales. In general the smaller the spatial scale the faster the time scale. The DE framework needs to simulate processes ranging from chloroplast level all the way up to leaf level. This may require approximation or response analysis of lower level processes when used as inputs for higher levels operating on time scales of a different order of magnitude. 2. Simulation of diverse physical phenomena within the 3-dimensional leaf anatomy. Various physical processes occur in a leaf. Gasses such as CO2 and water diffuse to and from ambient air through stomata into intercellular spaces, and ultimately to Rubisco. Active transport processes create concentration gradients from one cell type to another. Diffusion of metabolites dissipates these gradients. Events at leaf surface, such as stomatal opening, change the turgor pressure and mechanical forces within the leaf. The enlargement of bundle sheath cells requires changes in turgor pressure and cell wall deformation. The modeling framework must deal with all these processes simultaneously. 3. Network-based genetic interactions must be combined with a kinetic and mechanistic description of metabolism. Although metabolic reactions have a continuous response to inputs, gene expression can be discrete and stochastic. There is a strong interaction between these two processes. Genetic regulation constrains the potential capacity of metabolism. Metabolites affect gene expression and correspondingly the function of the gene interaction network. Although we have no automatic 11 methods to combine these processes now, we must incorporate genetic regulation into a model of metabolism. We anticipate that iPlant can provide the software engineering support for these developments, as well as hardware support for high performance computing facilities. Education, Outreach and Training Outreach and Training for the Plant Science Community This GC project can strive to develop computational and systems modeling skills plus increase the depth of quantitative understanding of photosynthesis within plant science community with a number of activities: • • • • Develop training materials and host training workshops (in the USA) for photosynthesis modeling. Provide travel funds for US scientists to international project-affiliated meetings (e.g. PICB, C4 rice consortium meetings, international photosynthesis conferences). Fund shuttle science exchanges into GC project development activities for international photosynthesis research team members such as photosynthesis modeling experts and graduate students/postdocs from outside the US. Develop (US) national curriculum resources for training in plant CI relating to computational systems biology modeling and photosynthesis research International collaboration between iPlant and photosynthesis research consortia like the C4 Rice Consortium (described previously, above) could include the sharing of expertise funded within the Consortium, at several levels of scientific exchange, including perhaps shuttle visits to iPlant development sites, subsidized by iPlant. Public Outreach and Training Green plants are pervasive on the surface of the planet, in all but the most arid or forbidding of locations. Despite the importance of plants to the basic human necessities of food, shelter and clothing few students currently give plants much thought. Aside from a cursory mention of photosynthesis in most high school science classes, few students enter university with the intent of studying plant science. At Cornell and many of our countries top universities, plant science and plant breeding departments are suffering a drop in student enrollments and decreases in federally-funded grant support for plant science research. This trend is particularly distressing at this time as the challenges of global warming, energy security and population growth demand that the best and brightest students choose plant science as a career path. It is also critical that the general public becomes more informed about plants when considering government policies on bioenergy, the costs (both economic and environmental) on chemical fertilizers and pesticides and the benefits and risks associated with genetically modified foods. The diversity of biology underlying photosynthesis is unknown to the great majority of people. Few are aware of the incremental increases in agricultural crop productivity. That there may be intrinsic limits to such productivity is a rarer idea still. The recent volatility in cereal crop prices, in particular for rice, renewed anxieties of the world of global food shortfalls. Parts of the world with large and growing populations still harbor significant pockets of poverty, and they demonstrate continuing, and in some cases growing, demands for cereals like rice and wheat. The prospect of C4-type photosynthesis increasing the productivity of key crops like rice and wheat is likely to fire the imagination and increase expectations. Concurrently, as the world continues to embrace “green” environmental ethics, one might foresee an increased curiosity of the biology of plants and photosynthesis. On a negative note, general backlash to the perceived shortfalls of the first so-called “Green Revolution” of the 1960’s, coupled with general wariness of “Genetically Modified Organisms” could be potential challenges to the success of a C4-type photosynthesis project. It will be recognized that the only available means of introducing C4-type photosynthesis into C3-type photosynthetic species is through transgenic technology. This proposed GC theme should embrace such interest, expectations, and perceived threats, by carefully crafting “CI-enabled” education and information specifically targeting photosynthesis. This would include a comparison C3–type versus C4–type photosynthesis; and suitable background to explain the 12 experimental and biotechnical processes being undertaken to achieve the project’s goal. These materials would be developed and delivered for many cognitive levels, such as primary, secondary, and postsecondary schools, for casual consumption by an educated lay public; or for serious consideration by potential critics. Part of DE development of this project could focus on creating a simplified simulator of leaf and/or whole plant photosynthesis, as a means for education. Summer workshops would be organized at US institutions to provide high school teachers with training in the tools developed through this DE (e.g. http://outreach-pgrp.cornell.edu/educationTeacherPrograms.php). With versions of increasing sophistication, such a simulator could be used as to train students in model building. “Summer schools” in plant photosynthesis modeling could be offered for high school or undergraduate students to participate in some of the laboratories developing or applying the iPlant CI for this GC project. Computer Science Needs for the Photosynthesis GC We have identified some general project needs that require targeted computer science expertise. First, many existing models of photosynthesis are specified in commercial packages, such as Matlab. Though these packages proved extremely useful in developing the reference model, they are usually expensive and not generally available to many bench scientists. Conversion of reference models into open source versions would increase access of the models to the wider community and students. In this project, we will use a two step process: i.e. first using existing packages such as MATLAB to develop reference models, and then develop generic packages to enable easy and efficient model developments. Second, parameter estimation algorithms (and their implementations) must be improved and modified for high-throughput data, such as the vast amount of transcript, proteomic and metabolomic data now available. Third, the modeling effort would benefit greatly from a 3-dimensional graphic representation of photosynthesis model inputs and outputs. Fourth, error estimation/summation and statistical analysis of the simulation results should be improved. Fifth, scaling model simulations from genome or cell to higher levels such as leaf segment to whole leaf may require execution on remotely hosted high performance cluster and/or grid computing facilities. Porting of the models to these facilities will require significant “hard core” computing expertise. Possible computational expertise (colleagues of GC proponents) available to assist with the development of the proposed photosynthesis DE includes: Mike Heath (NCSA, UIUC), Eric de Sturler (Virginia Tech), James Myers (NCSA, University of Illinois). Projected Bottlenecks and Difficult Steps In a second phase of this project, 3D multi-phenomenal and multi-scale simulation environments could be developed. This is an extremely ambitious CI challenge, thus we would expect the research and development effort required a substantial bottleneck to this GC. Experienced applied mathematicians and computer scientists will be invited to join the team to ensure the successful overcome of this difficulty. Project Implementation and Management Plan Appendices A1 and A2 provides a tabular log frame of the anticipated major project objectives, outputs, activities, stages, milestones and timelines for the project, with indications of core GC team member responsibilities. Project proponents will generally be available to various degrees to work with the iPlant team for all aspects of the CI software development cycle. Assuming that iPlant funding is provided for travel and local hosting costs, selected members of the GC team could undertake shuttle science visits to iPlant implementation sites (i.e. University of Arizona and/or Cold Spring Harbor Laboratory) which could include extended sabbatical visits for “hands-on” development of the GC project CI in partnership with core iPlant staff. For overall coordination of the project, we will hold monthly teleconferences to coordinate the work and convene annual meetings of project participants to review project progress, future work plans, including monitoring committee needs and plans. A scientific advisory committee (tentatively proposed to be composed of Mike Heath, Steve Long and Jim Myers) will monitor the progress of the project and advise the research of this overall project. 13 Intellectual Property Constraints We will develop open source software that will be freely available and used by research community. Data sets accessed and integrated in the project will be public and unencumbered by IP. Project Completion The timeline for this project is presented in Appendix A2. We envision a three different target time scales to reach different level of functionalities for the DE. Early work within the first 2 years of the project will focus on CI development using currently available “off-the-shelf” (bio)informatics and modeling tools and technologies. Within this scope, the outputs under objective 1 – web portal & data repository– should be significantly commissioned, and a substantial degree of analytical functionality should be available from outputs of objective 2 – the knowledge driven workbench. By that time, we should also have developed basic resources for education, outreach and training (objective 4). Objective 3 of building a simulation environment that can effectively simulate 3 dimensional reaction-diffusion systems, coupled with various biochemical and biophysical processes in one single cell, will require substantial cutting-edge research and development effort and is only targeted for substantial progress toward the end of a proposed five-year period. Beyond the end of the five-year funding period, we will start to move technology prototyped in the initial phases of the project, toward our vision of a simulation environment for multi-cellular system to serve the engineering of C4 photosynthesis. Summary: Projected Impact of the Photosynthesis GC The CI will greatly advance our capacity to solve two challenging problems in plant biology: a) enhancing photosynthetic efficiency in crop plants of agronomic importance; and b) converting agronomically important C3-type photosynthetic plants, such as rice and wheat, to use C4 photosynthesis. The CI we propose could be adapted to simulate other plant physiological processes, such as nitrogen fixation, respiration and other metabolic processes, dramatically improving the capacity of plant biology research in general. The C3 and C4 photosynthesis models developed here could form the basis for a generic plant primary metabolism model, which can be coupled to whole plant models to trace photosynthate utilization and simulate the metabolic processes of the whole plant. These models of photosynthesis could be used to evaluate how plant yield is limited by the response to external variables such as water and temperature stresses, changes in global CO2 and different local environments and crop management practices. In general, these models will contribute to our understanding of the responses of plants to abiotic stresses (cold, heat, drought etc) since photosynthesis is sensitive to these different environmental factors. Appendix A – Project Objectives, Activities, Outputs, Milestones and Timeline Appendix B – Additional Expert Resources for this Project Appendix C – Biological Data Sets Available to this Grand Challenge Project Appendix D – Curriculum Vitae of Project Proponent 14 References Cited: 1. FAOReport: The state of food and agriculture. (Weibe K ed. Rome, Italy: Food and Agriculture Organization of the United Nations; 2008. 2. von Braun J: The food crisis isn't over. Nature 2008, 456:701-701. 3. IFPRI Report [http://www.ifpri.org/pubs/fpr/pr20.pdf] 4. Dawe D: Agricultural research, poverty alleviation and key trends in Asia's rice economy. In Charting New Pathways to C4 Rice. Volume International Rice Research Institute. Edited by Sheehy JE, Mitchell PL, Hardy B. Los Banos, Philippines; 2007: 37-55 5. Sheehy JE, Ferrer AB, Mitchell PL, Elmido-Mabilangan A, Pablico P, Dionara MJA: How the rice crop works and why it needs a new engine. In CHARTING NEW PATHWAYS TO C4 RICE. Edited by Sheehy JE, Mitchell PL, Hardy B. Los Banos, Philippines: International Rice Research Institute; 2007: 3-26 6. Peng S, Laza RC, Visperas RM, Sanico AL, Cassman KG, Khush GS: Grain yield of rice cultivars and lines developed in the Philippines since 1966. Crop Science 2000, 40:307-314. 7. Mitchell PL, Sheehy JE: Supercharging rice photosynthesis to increase yield. New Phytol 2006, 171:688-693. 8. Mitchell PL, Sheehy: The case for C4 rice. In CHARTING NEW PATHWAYS TO C4 RICE. Edited by Sheehy JE, Mitchell PL, Hardy B. Los Banos, Philippines: International Rice Research Institute; 2007: 27-36 9. Zhu XG, Long SP, Ort DR: What is the maximum efficiency with which photosynthesis can convert solar energy into biomass? Curr Opin Biotechnol 2008, 19:153-159. 10. Paterson AH, Bowers JE, Bruggmann R, Dubchak I, Grimwood J, Gundlach H, Haberer G, Hellsten U, Mitros T, Poliakov A, et al: The Sorghum bicolor genome and the diversification of grasses. Nature 2009, 457:551-556. 11. Long SP, Zhu XG, Naidu SL, Ort DR: Can improvement in photosynthesis increase crop yields? Plant Cell Environ 2006, 29:315-330. 12. Zhu X, Portis AR, Jr., Long SP: Would transformation of C3 crop plants with foreign Rubisco increase productivity? A computational analysis extrapolating from kinetic properties to canopy photosynthesis. Plant Cell Environ 2004, 27:155-165. 13. Zhu X-G, Whitmarsh J, Ort DR, Long SP: Study of the effects of photoinhibition on dynamics of carbon uptake using reverse ray-tracing algorithm. J Ex Bot 2004, 55:1167-1175. 14. Zhu XG, de Sturler E, Long SP: Optimizing the distribution of resources between enzymes of carbon metabolism can dramatically increase photosynthetic rate: a numerical simulation using an evolutionary algorithm. Plant Physiol 2007, 145:513-526. 15. Raines CA: The Calvin cycle revisited. Photosynth Res 2003, 75:1-10. 16. Sage RF, Pearcy RW: The physiological ecology of C4 photosynthesis. In Photosynthesis: physiology and metabolism. Edited by Sharkey TD, von Caemmerer S. Dordrecht: Kluwer Academic Publishers; 2000: 497-532 15 17. Ogren WL: Photorespiration: Pathways, Regulation, and Modification. Annual Review of Plant Physiology 1984, 35:415. 18. Sage RF: The evolution of C4 photosynthesis. New Phytol 2004, 161:341-370. 19. Sage RF: Why C4 photosynthesis? In Sage RF and Monson RK (eds) C4 Plant Biology, pp 3--14. Academic Press, San Diego. 1999. 20. Vicentini A, Barber JC, Aliscioni SA, Giussani LM, Kellogg EA: The age of the grasses and clusters of origins of C4 photosynthesis. Global Change Biology 2008, 14:1-15. 21. Hibberd JM, Quick WP: Characteristics of C4 photosynthesis in stems and petioles of C3 flowering plants. Nature 2002, 415:451-454. 22. Nelson T, Langdale J: Developmental genetics of C4 photosynthesis. Ann Rev Plant Physiol Plant Mol Biol 1992, 43:25-47. 23. Stein LD: Towards a cyberinfrastructure for the biological sciences: progress, visions and challenges. Nat Rev Genet 2008, 9:678-688. 24. Bruskiewich R, Senger M, Davenport G: The generation challenge programme platform: semantic standards and workbench for crop science. Inter J of Plant Genomics 2008, 2008:6. 16 Appendix A – Project Management Plan Appendix A1 – Project Objectives, Activities, Outputs, Milestones and Resources Project iPlant Grand Challenge Project for Photosynthesis Research Vision of Success Within 10 years, crop improvement is significantly accelerated from advances in photosynthesis research made feasible by enhanced CI for photosynthesis research Objective 1 To establish a community portal for photosynthesis research Objective Leader: T. Brutnell Activity 1.1 Establish project Web 2.0 web portal. Activity Leader: T. Brutnell Outputs Milestones Outcome a. Web server commissioned. 1.1.1 Project web portal. b. Web portal software for prototype portal installed and configured. c. Photosynthesis web portal structure and content publicly reviewed by project photosynthesis experts. d. Web portal structure and content edited and maintained throughout project. Required Resources • “One stop shop” for photosynthesis information integrates and accelerates photosynthesis research globally. • • • Host location and hardware infrastructure for web server. Web 2.0 portal software. Programmer for web portal software deployment (6 programmer x months) Web portal manager (60 IT specialist x months) Objective 2 To establish a public data repository for photosynthesis research Objective Leader: P. Jaiswal Activity 2.1 Establish repository for photosynthesis molecular (“discrete”) data Activity Leader: P. Jaiswal Outputs Milestones Required Resources 2.1.1 Discrete photosynthesis data repository infrastructure. a. Database server hardware commissioned. b. Database platform software specify and installed. c. Overall photosynthesis database architecture, specified and Outcome • Discrete photosynthesis data repository established online for 24 x 7 research access by project stakeholders. • • Host location and hardware for database server. Database platform software. Information systems consultant (60 systems administrator x months) implemented. 2.1.2 Semantic standards for integration of photosynthesis research data. 2.1.3 Genomic map, sequence and candidate gene data module. 2.1.4 Transcriptomics data module. 2.1.5 Proteomics data module. 2.1.6 Metabolomics data module. 2.1.7 Project-related germplasm, phenotype and genotype (molecular variation) data module. 2.1.8 Research literature module. a. Public domain standards – domain models and ontology - for knowledge integration of photosynthesis research data, reviewed with community feedback. b. Baseline public ontology for photosynthesis, specified and published. c. Process established for continued community development and review of photosynthesis ontology. • Community semantic standards enables productive data mining of photosynthesis research data and information. a. Database schema and archives specified for raw and analyzed data, for discrete data input module. b. Standard operating procedures developed for data curation and quality assurance, annotation and exchange formats with Activity 3.1.1. c. Initial test data sets entered into data module. d. Initial normalized data sets created by reducing redundancy in principal objects being annotated/used in the analysis and cross-linked by creating links between different objects and entities by way of cross-references, orthology, parent-child relationships (lineage especially for germplasms) with Identifiers mappings back to entries inmajor public global repositories. c. Design and implement Web query and display interfaces. Enhanced research access to cross-linked data sets provides raw inputs to accelerate photosynthesis research. a. Schema and data loading tools specified and implemented for research literature module of the photosynthesis Photosynthesis research literature integrated with repository facilitates • • • • • • Web site for publication and review of semantic standards (collaboration with Output 1.1.1) Knowledge management consultant (6 bioinformatician x months) Workshop funding to convene discussions with photosynthesis researchers to validate project semantic standards. Information architect (24 bioinformatician x months) Programmer for development of data loading scripts (12 programmer x months) Data entry personnel (60 biologist x months) Systems analyst/programmer to develop research literature module (6 computer scientist x data repository. b. Research literature module of the photosynthesis data repository populated with an initial set of relevant scientific literature. c. Procedures established for community curation of additional publications into the research literature module of the photosynthesis data repository. photosynthesis research and knowledge management. • months) Librarian/manager for curation (24 person x months). Activity 2.2 Establish repository for photosynthesis physiological response (“continuous”) data. Activity Leader: M. Gent Outputs Milestones Outcome Required Resources 2.2.1 Physiological response photosynthesis (leaf) data repository structure. a. Data schema for continuous data input module specified. b. Repository populated with initial data sets. c. Web query and display interfaces designed and implemented. Photosynthesis (leaf) physiological response data research data integrated with repository facilitates photosynthesis research and knowledge management. • • • Information architect (12 bioinformatician x months). Programmer for development of data loading scripts (12 programmer x months). Data entry personnel (24 biologist x months) Activity 2.3 Establish repository for photosynthesis system models. Activity Leader: X. Zhu Outputs Milestones Required Resources Outcome • a. Data schema specified for process model repository. Photosynthesis process models indexed in the photosynthesis repository to facilitate collaboration using such models in photosynthesis research. 2.3.1 Photosynthesis system model repository. b. Web query and display to browse models and parameter sets, designed and implemented. Objective 3 To build a knowledge discovery environment for photosynthesis systems biology. • • Information architect (6 bioinformatician x months). Programmer for development of data loading scripts (6 programmer x months). Programmer for development of web query and display interfaces (6 programmer x months). Objective Leader: R. Bruskiewich Activity 3.1 Develop a semantic and software framework for development of a knowledge discovery environment for photosynthesis systems biology. Activity Leader: R. Bruskiewich Outputs Milestones Required Resources Outcome • 3.1.1 Semantic standards integrated into knowledge discovery environment. Methodology and strategy specified for embedding and using semantic standards (developed in Objective 2) in the knowledge discovery environment. Photosynthesis community semantic standards embedded in knowledge discovery environment enable productive data mining of photosynthesis research data and information. • • • 3.1.2 Data source access standards for photosynthesis data repository modules. a. Publicly available application programming interface (API) standards for data source access, reviewed for possible application to project. b. Project-specific data access standards and software libraries developed for photosynthesis data repository (developed in Objective 2). • Adoption of common project data source access standards enables efficient and interoperable access to photosynthesis repository data. • • 3.1.3 Access protocols to key (remote) online public biological (plant) data sources. a. Publicly available protocols for (remote) access to key public online biological (plant) data sources, reviewed for possible application to project. b. Project-specific access protocols and Adoption of project data source access standards enables efficient and interoperable access to relevant online (remote) public biological (plant) databases. • • Web site for publication of semantic integration into knowledge discovery environment (collaboration with Output 1.1.1) Systems analyst to design API (2 computer scientist x months) Programmer/designer to implement semantic aware software (6 programmer x months) Web site for publication and review of data source API (collaboration with Output 1.1.1) Systems analyst to design API (2 computer scientist x months) Knowledge management consultant (bioinformatician) to apply API for target query use cases against photosynthesis data modules (6 bioinformatician x months) Programmer/designer to implement data source access on data repository (24 programmer x months) Web site for publication and review of (remote) biological data sources access protocols (collaboration with Output 1.1.1) Systems analyst to design and software libraries specified and applied to key (remote) online public biological (plant) data sources. • 3.1.4 Data mining engine for project data. a. Publicly available data mining technology reviewed for application to photosynthesis repository and related public data sources. b. Project-specific data mining engine designed and implemented on top of the photosynthesis repository and related public data sources. 3.1.5 Application framework(s) specified for the development of a photosynthesis systems biology knowledge discovery environment. a. Open source software application development framework(s) reviewed for use in the development of photosynthesis knowledge discovery environment. b. Application framework(s) specified and implemented for the development of the photosynthesis knowledge discovery environment. 3.1.6 Web-based user interfaces to photosynthesis repository data. a. Publicly-available web technologies for data query and visualization, reviewed for possible use in web user interface to photosynthesis repository data. b. Design and implement baseline web interfaces for query and visualization of photosynthesis repository data. Web access to query and visualization tools for crosslinked photosynthesis repository data sets, and other available online public data, accelerates photosynthesis research. 3.1.7 Web-service publication of photosynthesis repository data. a. Publicly-available web-service publication protocols and technology reviewed for use in providing Programmatic web-service access to photosynthesis repository data allows linkage Project-specific data mining technology enables discovery, structuring and interpretation of available photosynthesis research data. Adoption of a standard software application framework will accelerate development of the photosynthesis systems biology knowledge discovery environment. implement protocols (12 computer scientist x months) Knowledge management consultant to apply protocols for target query use cases against target public databases (6 bioinformatician x months) • Information architect to design data mining software (6 computer scientist x months x months) • Web site for publication and review of project-specific application development framework(s) (collaboration with Output 1.1.1) Systems analyst/programmer to review technology options and implement selected framework (6 computer scientist x months) • • • • Web site for publication and review of web technologies for data query and visualization (collaboration with Output 1.1.1) Systems analyst/programmer to review technology options and implement selected framework (12 computer scientist x months) Web site for publication and review of web service publication protocols and programmatic web-service access to photosynthesis repository data. b. Web-service access to the photosynthesis data repository, designed and implemented. of analytical tools to photosynthesis research data and information. • technology (collaboration with Output 1.1.1) Systems analyst/programmer to review technology options and implement selected framework(s) (12 computer scientist x months) Activity 3.2 Develop text mining tools for photosynthesis knowledge discovery. Activity Leader: R. Bruskiewich Outputs Milestones Outcome Required Resources Text mining of photosynthesis research literature enables discovery of novel biological facts and relationships that accelerate photosynthesis research. • 3.2.1 Text mining module for photosynthesis knowledge capture from scientific literature. a. Text mining query and display engine operating on photosynthesis literature module (Output 2.1.7) and other related (online, remote) databases, using photosynthesis-specific ontology (Output 3.1.1), designed and implemented. b. Quality assurance methodology defined, for manual validation of results from text mining • Systems analyst/programmer to develop publications module (6 computer scientist x months) Biologists to read and validate the key data obtained from literature text mining. c. Pilot manual validation undertaken, of initial data sets obtained from the literature mining. Activity 3.3 Develop a data mining tool for photosynthesis knowledge discovery. Activity Leader: R. Bruskiewich Outputs Milestones Required Resources 3.3.1 General data mining query engine for photosynthesis data repository a. General data mining engine to operate on photosynthesis data repository (Activity 2.1), design and implemented. b. Statistical tools for comparative analysis of published data sets, designed and tested. c. Web interface for manual curation of new biological facts and relationships, Outcome • Data mining of photosynthesis data repository enables discovery of novel biological facts and relationships that accelerate photosynthesis research. • Information architect (bioinformatician) to specify baseline design (6 bioinformatician x months) Programmer/designer to implement data mining software (12 programmer x months) designed and implemented. Activity 3.4 Develop analytical tools for photosynthesis knowledge discovery. Activity Leader: R. Bruskiewich Outputs Milestones Required Resources 3.4.1 Sequence analysis tools. 3.4.2 Comparative genome (sequence level) and functional (expression level) alignment tools. 3.4.3 Inference tools for metabolic pathways, genetic (regulatory) network, proteinprotein interactions, and signal transduction Outcome a. Available open source sequence analysis and visualization tools and libraries reviewed for application to the knowledge discovery workbench. b. Sequence analysis and visualization tools specified and implemented accessing the photosynthesis data repository. a. Data schema for comparative genomic alignments, sequence diversity analysis and functional genomics, specified and implemented. b. Comparative query and visualization tools, specified and implemented c. Comparative query and visualization tools deployed on data sets developed from key completed genomes: Arabidopsis, Oryza sativa, Sorghum bicolor, Zea mays, Panicum virgatum (switchgrass). d. Comparative query and visualization tools deployed on molecular diversity (e.g. crop SNP) data sets. e. Comparative tools deployed on other available comparative data sets (e.g. plant transcriptome datasets) a. Data schema for pathway and network data module, designed and implemented. b. Analytical, inference and data visualization tool for metabolic • • Bioinformatics discovery of photosynthesis coding, regulatory motifs and biological functions in available sequence data. Enable inference of metabolic pathways, genetic (regulatory) network, protein-protein interactions, and signal transduction pathways • • • • Information architect (bioinformatician) to specify (2 bioinformatician x months) Programmer/designer to implement (6 programmer x months) Information architect (bioinformatician) to specify (6 bioinformatician x months) Programmer/designer to implement (24 programmer x months) Information architect (bioinformatician) to specify representation (12 bioinformatician x months) Programmer/designer to pathways. pathways, genetic (regulatory) network, protein-protein interactions, and signal transduction pathways, designed and implemented. 3.4.4 Facilities to combine time-series data of metabolites with gene and protein expression data. Ordinary differential equation modeling approaches, integrated with a statistical inference approaches, specified and implemented. Objective 4 Develop a simulation environment for systems modeling of photosynthesis metabolism and differentiation. Objective Leader: X. Zhu Activity 4.1 Develop the simulation environment for kinetic modeling of photosynthesis metabolism and differentiation (will not consider the spatial differentiation) Activity Leader: X. Zhu Outputs Milestones Required Resources 4.1.1 Simulation application for kinetic modeling of photosynthesis metabolism. a. Programming technology selected for dynamic modeling of metabolism. b. Tools developed to enable graphic representation of metabolic processes and define the kinetic information. c. Simulation environment implemented for automatic generation and solving differential equations. d. Visualization tools designed and implemented to show the dynamic changes of metabolic activities on a pathway. e. Evolutionary algorithms developed to identify optimize photosynthesis 4.1.2 Simulation application for kinetic modeling of differentiation of photosynthetic machinery a. Simplified model of photosynthetic machinery differentiation, designed and implemented. b. Plug-and-play capacity develop to explore variations of photosynthetic properties under different environments implement analytical tool (24 programmer x months) underlying photosynthesis. • • Outcome • • Development of a common simulation platform to simulate photosynthesis will integrate and accelerate photosynthesis research and help identify gene targets for crop improvement. • • Mathematician/bioinformatician to help design algorithms (6 bioinformatician x months) Programmer/designer to implement data mining software (12 programmer x months) Postdoctoral photosynthesis scientist Programmer/designer (s) to develop model environment, simulation environment and plug and play functionality (15 programmer x months) Postdoctoral photosynthesis scientist Programmer/designer (s) to develop model environment, simulation environment and plug and play functionality (6 programmer x months) 4.1.3 Simulation integrated model of photosynthesis metabolism and differentiation events • a. A photosynthesis model developed combining model from Output 4.1.2 with metabolism and genetic regulatory networks for photosynthesis b. Photosynthesis model developed with signal transduction pathway integrated with metabolism and genetic networks • • Mathematicians to help design algorithms for control circuit identification Biologists to help extract the initial genetic network and regulatory pathways Programmer/designer (s) to develop model environment, simulation environment (12 programmer x months) Activity 4.2 Develop the auxiliary algorithms to facilitate application of the systems models and link models to databases Activity Leader: C. Myers Outputs Milestones Required Resources 4.2.1 Analytical support functions applied to the photosynthesis simulation environment. a. Parameter estimation algorithm for simulation environment, specified and implemented. b. Optimization algorithms applied for the simulation environment. c. Software developed to visualize the ordinary differential equation solution space and identify regions with high biological relevance d. Methods specified and applied to conduct bifurcation analysis of kinetic models. Systems biology application tools available to enable plant scientists connect models with experiments for hypothesis testing. 4.2.2 Develop kinetic modeling framework. Kinetic models linked with physiological response data and time series metabolomics data to estimate model parameters. Model predicting evolution over time or development of metabolites involved in photosynthesis. 4.2.3 Link photosynthesis discrete database with kinetic modeling framework. a. Genome transcriptome and metabolome level data link to parameters in integrated model of Direct linkage of the modeling environment with data assembled in the Outcome • • • • • Applied mathematician skilled in non-linear parameter estimation and least squares minimization algorithms. Programmer/designer to integrate existing tools for parameter estimation, optimization, and visualization, and bifurcation analysis (12 programmer x months) Principal leaders and applied mathematician debate/review methods for this linkage. Programmer/designer to implement linkage tool (6 programmer x months) Principal leaders and applied mathematician debate/review methods for this linkage. photosynthesis metabolism and regulation. b. Kinetic modeling combined with genomic data to evaluate significance of genomic variations to photosynthetic efficiency and differentiation photosynthesis data repository, enables identification of genetic basis for photosynthetic metabolism and regulation. • Programmer/designer to implement linkage tool (24 programmer x months) • Principal leaders and applied mathematician debate/review methods for this section. Programmer/designer to implement selection tool (12 programmer x months) 4.2.4 Manage dynamic model development to maintain tractability and ease of use. a. Model reduction methods developed to select and eliminate parameters and/or network interactions to maintain a relatively robust dynamic model b. Algorithms developed to define response surface of interacting networks to use model upscaling. 4.2.5 Cross-link photosynthesis models to data repository for model validation. a. Interface designed to cross-link models in model repository (Output 2.3.1) with discrete, continuous and anatomical data sets, to enable direct comparison of model results with data sets elsewhere in the repository. Activity 4.3 Develop the basic 3 dimensional reference models for photosynthetic metabolism and differentiation Activity Leader: X. Zhu Outputs Milestones Required Resources 4.3.1 Implement a reference 3 D photosynthesis model a. A 2 dimensional C3 photosynthesis model implemented for single cell b. A 3D C3 photosynthesis model implemented for single cell c. Tools developed to visualize the 3D leaf, cell and sub-cellular compartment, with defined physical and chemical properties. Development of for a reference 3D model of photosynthesis. 4.3.2 Develop a reference model integrating C3 carbon fixation process and differentiation of photosynthetic apparatus A detailed photosynthetic carbon metabolism network developed, incorporating subcellular compartmentalization and organelle structure. Develop a model of photosynthesis metabolism and differentiation with detailed consideration of the 3 dimensional anatomical Kinetic models that incorporate multiple discrete data yet maintain enough simplicity for use by biological scientists. • • Researchers can compare model expectations against experimental realities. Outcome • • • • • Principal leaders to debate/review methods for this section. Programmer/designer to implement selection tool (12 programmer x months) Mathematicians to help develop of the 3D photosynthesis model Programmer/designer to implement the model (12 programmer x months). Mathematicians to facilitate the design of the multiscale modeling framework Programmer/designer to implement the modeling structure of organelle environments (12 programmer x months). 4.3.3 Develop a reference 3D leaf photosynthesis model to simulate the photosynthetic processes and differentiation a. A 3D photosynthesis model implemented for a typical leaf, including the energy balance and gas exchange at the leaf surface b. Methodology developed to dissect contribution of anatomical and kinetic parameters in the regulation of photosynthesis c. Existing modeling packages used to implement a reference 3D photosynthesis differentiation model d. Potential approaches identified to differentiate photosystem with C4 characteristics Activity 4.4 Develop reference models to simulate metabolite transport, cell development and expansion in a photosynthetic leaf tissue and develop connection of models to genomic databases Activity Leader: M. Gent Outputs Milestones Required Resources 4.4.1 Simulation environment to simulate leaf photosynthesis process with detailed consideration of metabolite transport a. Algorithms designed to enable design of cells with different physical properties, shapes, chemical reactions and detailed consideration of metabolite transport b. Algorithms designed to link discrete/stochastic processes with continuous processes c Visualization tools developed to visualize simulation results in a 3 D space. A realistic simulation environment for a 3D multicellular system with detailed metabolite transport properties 4.4.2 Simulation environment for differentiation, development and cell expansion in leaf tissues a. Algorithms developed to link physical processes, cell wall expansion and osmotic pressure, to expansion of cells. b. Cell development and expansion processes included in kinetic models Simulation of the process of growth and differentiation within leaf tissue. • Development of a reference leaf photosynthesis and differentiation model. Outcome • • • • • Mathematicians to help develop the 3D leaf photosynthesis model Programmer/designer to implement the model (24 programmer x months). Applied mathematician to consult on coupling processes in different cells. Programmer/designer to implement resulting algorithms (24 programmer x months) Applied mathematician to consult on physics of expansion. Programmer/designer to implement resulting algorithms simulation environment. c. Algorithms for influence of cell-cell contact and geometry on cell development/expansion, designed and implemented. (12 programmer x months) • 4.4.3 Link photosynthesis discrete database with modeling framework for cell structure and development. a. Genome, transcriptome and metabolome level data linked to parameters in physical model to facilitate functional genomics of cell development and expansion b. Interface developed to allow asking “what if” questions Direct linkage of the modeling environment with data assembled in the discrete photosynthesis. data repository, enables identification of genetic basis for photosynthetic processes and provides targets for crop improvement. • • Principal leaders and applied mathematician debate/review methods for this linkage. Biologist/bioinformatician to assist with linkage of genomic information to the models (12 bioinformatician x months) Programmer/designer to implement resulting algorithms (24 programmer x months) 4.4.4 Manage dynamic cellbased model development to maintain tractability and ease of use. a. Methods developed to select and eliminate parameters and/or network interactions to maintain a relatively robust dynamic model b. Algorithms designed and implemented to define response surface of interacting networks for use in higher levels of integration. Activity 4.5 Develop a generic 3D multi-scale and multi-phenomena modeling framework enable plug-and-play design of photosynthesis systems Activity Leader: S.K. Lu Outputs Milestones Outcome Required Resources 4.5.1 Simulation environment for modeling a reaction diffusion system in a 3D space a. Major algorithms identified for 3 dimensional modeling of reaction diffusion system. b. Tools implemented to design 2 dimensional objects with defined physical properties c. Basic modeling platform implemented for 3 dimensional reaction diffusion system that will enable input of user designed reaction equations in the Development of a basic modeling platform for 3 dimensional modeling of typical reaction diffusion systems assists in research understanding of spatial aspects of photosynthesis. • Cell models that incorporate multiple discrete data yet maintain enough simplicity for use by biological scientists. • • • Principal leaders and applied mathematician debate/review methods for this selection. Programmer/designer to implement selection tool and response surface algorithms (6 programmer x months) Mathematicians to facilitate the design of the simulation environments Programmer/designer to implement the modeling environments (24 programmer x months) particular objects; d. Generic system implement for the reference model of leaf photosynthetic metabolism. e. Effective visualization tools implemented to show the 3 D structure and anatomy. 4.5.2 Develop support capacities to enable simulation of complex reaction diffusion systems by biologists without computational expertise a. Simulation package parallelized to use high performance computers b. Simulation interface designed to enable users to design leaf with different cell shapes, distribution, organelle shapes and distribution, physical properties, c. Algorithm designed for parameter estimation based on model and time series measurement data d. Generic algorithms developed to connect 3D models to genomic databases The implement of the photosynthesis simulation environment is supported by high performance computers and enables users to efficiently simulate a system with userdefined structure and kinetic properties • • Mathematicians to help parallelize the algorithms developed in 3.5.1 Programmer/designer to implement the simulation environments (24 programmer x months). Objective 5 Develop resources for education, outreach and training relating to photosynthesis science. Objective Leader: T. Brutnell Activity 5.1 Establish online web portal site for education, outreach and training. Activity Leader: T. Brutnell Outputs Milestones Outcome Required Resources 5.1.1 Establish project web portal section for education, outreach and training Design and implement baseline Web site for photosynthesis GC education, outreach and training. “A one-stop-shop” for GC education, outreach and training about photosynthesis science is a valuable resource for public and academic science education. Outreach Coordinator with masters or PhD in education to interface with project team members (36 months) Activity 5.2 Implement a capacity building strategy for photosynthesis research. Activity Leader: T. Brutnell Outputs Milestones Required Resources 5.2.1 Online training a. Develop and publish training Outcome • PhD-level plant scientists • Web site for publication. materials and training workshops (in the USA and international partner institutes) for photosynthesis modeling. materials for photosynthesis modeling. b. Convene annual training workshop for photosynthesis modeling. • Graphic designer? Educator to organize workshops. Travel expense subsidies (participants could/should also contribute from their own budgets) • • Travel expenses. Meeting expenses • • • trained in computational and systems biology. Computer science biology, mathematics and physics students recruited to the field plant science A new generation of graduate students will be trained who will be defined by multidisciplinary skills in computational biology and plant science. 5.2.2 US scientists’ participation in international project-affiliated meetings and training workshops (e.g. PICB, C4 rice consortium meetings, international photosynthesis conferences). US scientists participate in international project-affiliated meeting. 5.2.3 Meetings of international photosynthesis research team members, photosynthesis experts, and graduate students/postdoc from outside the US. Shuttle science exchange undertaken for GC project development. 5.2.4 National high school curriculum resources for introduction to photosynthesis research. a. Design and publish national high school curriculum for photosynthesis research. b. Pilot high school curriculum at teacher training workshop c. Publish national high school curriculum for broad dissemination. High school students encouraged to experience plant biology as a technologically exciting and relevant career choice. 5.2.5 National college-level curriculum resources for university training in plant CI relating to computational systems biology modeling and photosynthesis research. a. Design and publish national collegelevel curriculum for computational systems biology modeling and photosynthesis research. b. Pilot high school curriculum at selected university sites. c. Publish national college curriculum College level graduates of biology are better equipped to apply computational techniques and knowledge about photosynthesis, in their professional career. • Travel and meeting expenses. • • • • • • Educators to specify/design curriculum in concert with Principal leaders. Graphic designer? Editor/publisher for initial and final product. Educators to specify/design curriculum in concert with Principal leaders. Graphic designer? Editor/publisher for initial and final product. for broad dissemination. Activity 5.3 Develop and dissemination resources for public education, outreach and training about photosynthesis. Activity Leader: T. Brutnell Outputs Milestones Outcome Required Resources 5.3.1 General public information resource on photosynthesis and the project. a. Establish general public information resource on photosynthesis, populated with baseline information. b. Annually update public information resource on photosynthesis and this project. • • 5.3.2 A simplified educational simulators of leaf and/or whole plant photosynthesis, targeting elementary and secondary school level students. Design and implement a public interface to get access to the photosynthesis simulation environment developed via this project for educational purposes. Inform public on GMOs Provide public interface for questions on photosynthesis and crop productivity (food, feed, fiber and bioenergy) K – 12 students and general public learn about photosynthesis and computational biology by simple and entertaining hands on computational experimentation. • • • • Web site to present information to the general public. Web designer/manager to maintain Web site. Web site to host educational simulator for public access. Programmer/designer to implement simulator and web interface (12 programmer x months) Appendix A2 – Project Timeline Activity Year 1 Objective 1 To establish a community portal for photosynthesis research 1.1. Establish project Web 2.0 web portal (Lead T. Brutnell) Objective 2 2.1. Establish repository for photosynthesis molecular data (Lead P. Jaiswal) Web server established and software installed Objective 3 3.1. Develop a semantic and software framework for development of a knowledge discovery environment (Lead R. Bruskiewich) Web server populated and reviewed by community Year3 Implement web portal for public outreach Web portal structure and content edited and maintained throughout project To establish a public data repository for photosynthesis research Overall database architecture, specified and implemented -Omics database modules developed Research literature module developed Germplasm, phenotype and genotype (molecular variation) data modules developed Semantic standards for integration of photosynthesis data implemented 2.2. Establish repository for photosynthesis physiological response data (Lead M. Gent) 2.3. Establish repository for photosynthesis system models (Lead X. Zhu) Year2 Design and implement a database for physiological response data with steps as in 2.1 Develop algorithms to extract kinetic parameters from response curves Develop methodology and strategy for embedding and using semantic standards in the knowledge discovery environment Implement access protocols to key (remote) online public biological (plant) data sources Develop data source access standards for photosynthesis data repository modules Implement project-specific data mining technology Initiate integration of germplasm, phenotype and genotype (molecular variation) data modules with omics modules Integrate physiological response database with – omics databases,and model repository Data schema specified for process Web query and display to browse Continue development of model repository models and parameter sets, integration of each repository designed and implemented defined under objective 2 To build a knowledge discovery environment for photosynthesis systems biology Continue development of open source software framework to support photosynthesis systems biology knowledge discovery environment Continue development of web-service access to repository data for linkage of analytical tools to research data Develop data source access standards for photosynthesis data repository modules Develop framework for integrating discrete and continuous data in repositories and models Develop text mining query and display engine operating on literature module and related databases Define quality assurance methodology Implement project-specific data mining technology 3.3. Develop data mining tools for photosynthesis knowledge discovery (Lead R. Bruskiewich) 3.4. Develop analytical tools for photosynthesis knowledge discovery (Lead R. Bruskiewich) Design and develop general data mining engine to operate on photosynthesis data repository Develop and integrate statistical tools for comparative analysis of data sets Review, integrate, and develop sequence analysis and visualization tools Develop schema for comparative genomics, sequence diversity, and functional genomics data Develop schema for pathway and network data module Develop and deploy comparative query and visualization tools Objective 4 To develop a simulation environment for systems modeling of photosynthesis metabolism and differentiation 4.1. Develop the simulation environment for kinetic modeling of photosynthesis metabolism and differentiation (Lead X. Zhu) 4.2. Develop the auxiliary algorithms to facilitate application of the systems models and link models to databases (Lead C. Myers) Develop a simulation application for kinetic modeling of metabolism and photosynthetic machinery Develop a simulation model that integrates models of machinery and metabolism Cross-link photosynthesis models to data repository for model validation Optimize parameter estimation algorithms based on discrete data. Integrate existing tools with simulation environment. Develop algorithms for linking discrete/stochastic processes with continuous processes Develop software for linking discrete databases with kinetic modeling framework to allow for automated model construction as new data become available. Explore strategies for model reduction based on parameter sensitivities and response surfaces. 3.2. Develop text mining tools for photosynthesis knowledge discovery (Lead R. Bruskiewich) Continue development of web-service access to repository data for linkage of analytical tools to research data Pilot manual validation undertaken, using initial data sets used from literature mining Develop analytical, inference and data visualization tool for biological networks Develop web interface for manual curation of new biological facts and relationships Continue deployment of comparative tools on other available data sets Develop and integrate tools for combining time-series data of metabolites with gene and protein expression data 4.3. Develop basic 3dimensional reference models for photosynthetic metabolism and differentiation (Lead X. Zhu) Implement 2-and 3-dimensional C3 photosynthesis models for a single cell 4.4. Develop simulation model for leaf photosynthesis with consideration of metabolite transport (Lead M. Gent) Integrate algorithms for membrane transport in kinetic models of metabolism 4.5. Develop a generic 3D multi-scale and multiphenomena modeling framework enable plug-andplay design of photosynthesis systems (Lead S. K. Lu) Objective 5 5.1. Establish online web portal site for education, outreach and training (Lead T. Brutnell) 5.2. Implement a capacity building strategy for photosynthesis research (Lead T. Brutnell) Identify major algorithms for 3D modeling of reaction-diffusion systems, and develop tools for basic 2D and 3D simulation Develop tools for 3D, multiscale leaf visualization Develop a model of photosynthesis metabolism and differentiation with detailed consideration of the 3 dimensional anatomical structure of organelle Development of a reference leaf photosynthesis and differentiation model Generate a realistic simulation environment for a 3D multicellular system with detailed metabolite transport properties Generate a model to simulate the process of growth and differentiation within leaf tissue Develop generic system implementation for reference model of leaf photosynthetic metabolism Develop capabilities for simulations of complex reaction diffusion systems, including parallelization, visualization, parameter estimation, etc. Develop algorithms for linking discrete/stochastic processes with continuous processes To develop resources for education, outreach and training related to photosynthesis science Hire outreach coordinator and begin Design and implement baseline Release public simulator for development of photosynthesis Web site for photosynthesis GC modeling photosynthesis (see curriculum modules education, outreach and training Objective 1) Develop and publish training materials for photosynthesis modeling Convene annual training workshop for photosynthesis modeling Convene high school teacher training workshops and develop curriculum modules distributed over web portal Support US scientists’ participation international project-affiliated meetings and training workshops, and meetings of international photosynthesis research team members from outside the US 5.3. Develop and disseminate resources for public education, outreach and training about photosynthesis. (Lead T. Brutnell) Develop and annually update general public information resource on photosynthesis and the project outreach and training about photosynthesis. (Lead T. Brutnell) Develop and refine simplified educational simulators of leaf and/or whole plant photosynthesis, targeting elementary and secondary school students Appendix B – Additional Expert Resources for this Project Participant Joseph Berry Ken Boote Jerry Edwards Alistair Fernie Bob Furbank Bill Green Vincent Gutschick Mike Heath, Julian Hibberd Title & Affiliation Professor, Department of Global Ecology Carnegie Institution of Washington, USA Professor, Agronomy Department, University of Florida, Gainesville, FL Professor Biological Sciences Washington State University Pullman, WA, USA Group Leader, Max Planck Institute of Molecular Plant Physiology (MPIMP), Golm, Germany Senior Principal Research Scientist/Project Leader, CSIRO Plant Industry, Canberra, Australia Professor, Massachusetts Institute of Technology, USA Professor, Department of Biology, New Mexico State University, Las Cruces, NM Professor, Department of Computer Science, University of Illinois at Urbana Champaign, IL Senior Lecturer, Department of Plant Sciences, University of Cambridge, Cambridge, UK Raquell Holmes Assistant Professor of Cell Biology, University of Connecticut Health Center, Farmington, CT Peter Horton Department of Molecular Biology and Biotechnology, Universitiy of Sheffield, Sheffield UK Andrew Leakey Assistant Professor Department of Plant Biology, University of Illinois at Urbana Champaign,USA Expertise/Role Physiological means by which plants adapt to environmental stress and climactic change, and photosynthetic mechanisms used by higher plants and algaes to fix carbon dioxide. Measurement and modeling of canopy photosynthesis and crop growth, effect of environment and water stress. C4 photosynthesis, single-cell C4 photosynthesis, C4 pysiology Central metabolism Genetic manipulation of carbon partitioning and photosynthesis in crop plants, plant phenomics and imaging plant performance, mechanisms of drought tolerance in cereals. Analysis methodology for error management, robustness, range and sensitivity of results to errors (error bars) in the input. Plant water use, drought physiology and ecology, photosynthesis, process based mathematical models. Numerical computing Evolution of C4 photosynthesis; Role of proteins that have been co-opted into the C4 pathway in C3 species; Alterations in gene expression associated with the C4 pathway Cell & Computational Biologist / Development and application of dynamic simulators to understand biological systems – geometry, networks and pathways - at the cellular level. Photosynthetic electron transport Plant responses in natural and agricultural ecosystems to global climate change and abioitic stress. Genomic regulation of plant ecological strategy. Richard Leegood Hua-Ling Mi Steve Long ZengRong Liu, Congming Lu Jim Mattson Andrew Millar Erik Murchie Timothy Nelson Christoph Peterhänsel Richard Peterson, Donald Ort Rowan Sage Tom Sharkey Senior Lecturer, Department of Animal and Plant Sciences, University of Sheffield Professor, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, USA Professor of Crop Sciences, Robert Emerson Professor, and Resident Scientist for the National Center for Supercomputing Applications, University of Illinois Professor, Department of Mathematics, Shanghai University, China Professor, Photosynthesis Research Center, Institute of Botany, Chinese Academy of Science, China Assistant Professor, Simon Fraser University, Burnaby, BC, Canada Professor & Chair of Systems Biology, Institute of Molecular Plant Sciences School of Biological Sciences University of Edinburgh, Edinburgh, Scotland, UK Division of Plant and Crop Sciences, School of Biosciences, University of Nottingham, Sutton Bonington, UK Professor, Yale University Research Group Leader, University of Aachen, Germany Agricultural Scientist, Department of Biochemistry & Genetics Connecticut Agricultural Experiment Station, Professor of Plant Biology, USDA/ARS Photosynthesis Research Unit, Adjunct Professor of Crop Sciences, Department of Plant Biology, University of Illinois, USA Professor and Chairman, Department of Botany (Plant and Microbial Biology), University of Toronto, Ontario, Canada Professor and Chair Dept. Biochem. Mol. Biol. Regulation and control of photosynthetic carbon and nitrogen metabolism Protein-protein Interactions in chloroplasts Plant Physiology, Environmental Science Applied mathematics Photosynthesis of rice and wheat, Photoinhibition and photoprotection, Molecular physiological mechanisms of photosynthesis under environmental stress Genetic regulation of vascular tissue development in plants Molecular & Systems Biologist / Image and related measurements of transcription and signal transduction in Arabidopsis plants wild type and mutant (transgenic) relative to circadian rhythms Rice photosynthesis and crop productivity Developmental genetics for plant leaf development and photosynthesis. Genetic engineering of photorespiration in Arabidopsis, regulation of photosynthetic gene expression in maize Measurement of gas exchange and photorespiration, biophysics of photosynthetic electron transport. The effect that specific environmental factors and abiotic stresses have on the photosynthetic performance of crop plants. C4 plants and their evolution; plant physiological ecology; mechanisms of plant response to global climate change; comparative photosynthesis of C3 and C4 plants; stress physiology; water relations; mechanisms affecting productivity, competition, and species distributions Plant-atmosphere interactions; isoprene emission; photosynthesis, especially carbon metabolism; plant Bob Turgeon Klaas van Wijk Susanne von Caemmerer Peter Westhoff Andreas Weber Sheng Zhong Michigan State University Professor, Department of Plant Biology, Cornell University, USA Associate Professor, Department of Plant Biology, Cornell University Professor of Molecular Plant Physiology, Research School of Biological Sciences, The Australian National University, Canberra, Australia Dean of the Faculty of Science, Department of Biology – Botany, Heinrich Heine University Düsseldorf, Düsseldorf, Germany Professor and Chair Institute of Plant Biochemistry Heinrich-Heine-University, Germany Assistant Prof. Bioengineering Department, University of Illinois at Urbana Champaign, USA biochemistry and biophysics Long-distance nutrient transport in the phloem, leaf development, and the structure and function of plasmodesmata, the fine pores that connect plant cells Plant Physiology, Plant Molecular Biology, Plant Biochemistry Physiology and biochemistry of photosynthesis; mathematical modeling of photosynthetic processes; analysis of photosynthesis and stomatal physiology by genetic manipulation; stable isotope fractionations in plants Evolution of genes and enzymes related to C4 photosynthesis; genetic transformation of C4 plants The study of transport processes that connect the metabolic pathways in plastid and cytosol, in particular those transporters involved in carbon- and nitrogen-metabolism, using biochemistry, molecular biology, and molecular plant physiology. systems modeling, machine learning, statistical methods. Appendix C - Biological Data Sets Available to this Grand Challenge Project Category Type Specific Available Data Specific Sources • Annotated rice genome assembly Annotated Reference Genomic Assemblies Structural Genomics Molecular Variation Annotated sorghum genome assembly • • JGI (Phytozome) Sorghum Genome Assembly (http://www.phytozome.net/sorghum.php) SorghumDb (http://algodon.tamu.edu/sorghumdb.html) Annotated maize genome assembly • • Maize Sequencing Project (http://www.maizesequence.org) Maize Assembled Genomic Island (http://magi.plantgenomics.iastate.edu/) Sequence variation in rice • OryzaSNP (www.oryzasnp.org) Sequence variation in sorghum • Sorghum Diversity Database (http://sorghumdiversity.org/sorghum/research.html) Sequence variation in maize • Panzea (http://www.panzea.org/) • Gramene’s diversity module (http://www.gramene.org/db/diversity/diversity_view) • Gramene Comparative Plant Genome Database (http://www.gramene.org/genome_browser/index.html ) • • Arabidopsis Information Resource (TAIR ; www.arabidopsis.org) Gramene Comparative Plant Database (http://www.gramene.org/genome_browser/index.html ) Genetic diversity and Alleleic polymorphism Comparative Sequence Alignments • • NSF-funded Rice Genome Annotation project (http://rice.plantbiology.msu.edu/) Rice Annotation Project (http://rapdb.dna.affrc.go.jp/) Rice Information System (http://rice.genomics.org.cn/rice/index2.jsp) Whole plant genome comparison, genome and genewise alignments, comparison to genetic maps, – rice, maize, sorghum, poplar, grape, Arabidopsis, wild rice, sequence alignments Model Plants • Rice gene expression Molecular Expression Comparative transcriptome, proteome and metabolome for rice, sorghum and maize (C4 leaf cell specific assays) Plant Expression datasets Functional Genomics Survey for C4 photosynthesis characteristics in wild rice species and cultivated rice subtypes Phenotypic analyses • • Yale “rice atlas” transcriptome data NSF-funded project, Comparative Analysis of C3 and C4 Leaf Development in Rice, Sorghum and Maize (http://C3C4.tc.cornell.edu/ and http://www.nsf.gov/awardsearch/showAward.do?AwardNumber= 0701736) • PlexDB (www.plexdb.org ) • International Rice Research Institute (IRRI) project data set measuring leaf vein spacing, CO2 compensation point and other characteristics in a large collection of wild rice genetic resource accessions OryzaSNP genotyped Oryza sativa germplasm set (www.oryzasnp.org ) • • Sorghum C3 revertant mutants Photosynthesis Physiology • • Gene Regulation Plant gene promoter databases Plant Physiology Leaf anatomy, biochemistry, metabolic flux data, physiology data NSF Rice Oligonucleotide Array Project (http://www.ricearray.org/) Rice MPSS (http://mpss.udel.edu/rice/) Rice Expression Database (http://red.dna.affrc.go.jp/RED/) • International Rice Research Institute (IRRI) project data set screening EMS mutants for disrupted vein spacing and photosynthesis USDA-ARS Plant Stress and Germplasm Development Unit, EMS Sorghum Mutant Population (www.lbk.ars.usda.gov/psgd/sorghum/till) • http://www.arabidopsis.org/portals/genAnnotation/genome_annot ation_tools/cis_element.jsp • Published photosynthesis literature and associated crop and leaf physiology data sets Shanghai Institute of Biological Sciences IRRI wild rice measurements (CO2 compensation points, vein spacing) • • Thomas P. Brutnell [email protected] Professional Preparation: University of Connecticut Yale University University of Oxford, UK Biology Biology Plant Sciences Appointments: Associate Scientist Adjunct Professor Assistant Scientist BBSRC David Phillips Research Fellow Postdoctoral Associate NIH Research Assistantship University Honors Scholar Phi Beta Kappa awarded Boyce Thompson Institute Cornell University Boyce Thompson Institute University of Oxford University of Oxford Yale University University of Connecticut University of Connecticut B.S., magna cum laude 1989 Ph.D. 1995 1995-1999 Jan.2006 – present 2000 - present Dec.1999 – 2005 1997 -1999 1995 -1997 1993 -1995 1989 1989 Related Publications: Zelitch, I., N.P. Schultes, R.B. Peterson, P. Brown and T.P. Brutnell (2009) High glycolate oxidase activity is required for survival of maize in normal air. Plant Physiol 149:195-204. Covshoff, S., W. Majeran, P. Liu, J.M Kolkman, K.J. van Wijk and T.P. Brutnell (2008) Deregulation of maize C4 photosynthetic development in a mesophyll cell-defective mutant. Plant Physiol 146:14691481. Sawers, R.J.H., P. Liu, K. Anufrikova, J.T.G. Hwang and T.P. Brutnell (2007) A multi-treatment experimental system to examine photosynthetic differentiation in the maize leaf, BMC Genomics 8:12. Sawers R.J.H., P.R. Farmer, P. Moffett and T.P. Brutnell (2006) In planta transient expression as a system for genetic and biochemical analyses of chlorophyll biosynthesis. Plant Methods 2:15. Garg, A.K., R.J.H. Sawers, H. Wang, J.-K. Kim, J.M. Walker, T.P. Brutnell, M.V. Parthasarathy, R.D. Vierstra, and R.J. Wu (2006) Light-regulated overexpression of an Arabidopsis phytochrome A gene in rice alters plant architecture and increases grain yield. Planta 223: 627-636. Significant Publications: Harjes, C.E., T.R. Rocheford, L. Bai, T.P. Brutnell, C.B. Kandianis, S.G. Sowinski, A.E. Stapleton, R. Vallabhaneni, M. Williams, E.T. Wurtzel, J. Yan, E.S. Buckler (2008) Natural genetic variation in lycopene epsilon cyclase tapped for maize biofortification. Science 319:330-333. Conrad, L.J., L. Bai, K. Ahern, K. Dusinberre*, D.P. Kane* and T.P. Brutnell (2007) State II Dissociation (Ds) element formation following Activator (Ac) excision in maize, Genetics 177:737-747. Sheehan, M.J., L.M. Kennedy*, D. Costich and T.P. Brutnell (2007) Subfunctionalization of PhyB1 and PhyB2 in the control of seedling and mature plant traits in maize. Plant J. 49:338-353. Bai L, M. Singh, L. Pitt*, M. Sweeney* and T.P. Brutnell (2007) Generating novel allelic variation through Activator insertional mutagenesis in maize. Genetics 175:981-992. Sawers R.J., J. Viney, P.R. Farmer, R.R. Bussey*, G. Olsefski*, K. Anufrikova, C.N. Hunter and T.P. Brutnell (2006) The maize Oil yellow1 (Oy1) gene encodes the I subunit of magnesium chelatase. Plant Mol Biol 60: 95-106. * undergraduate students supported through NSF funding Synergistic Activities: Outreach Activities I led development of a Cornell Summer Internship Program that served as a foundation for our current REU program at Cornell (http://www.bti.cornell.edu/educationInternships.php). I have also developed a high school teacher training program (http://www.bti.cornell.edu/educationTeacherPrograms.php) with the goal of introducing concepts of plant genomics research into the high school science curriculum. These programs have been developed to encourage interaction between research scientists, students and educators and increase the participation of students from traditionally underrepresented groups in NSF-funded research. Scientific Service 2007 – present Member, Maize Genetics Executive Committee 2008 Chair, Maize Genetics Conference Steering Committee 2006 – present Associate Editor, Genetics 2005 – present Consultant, Monsanto 2005 – 2007 Panel Member, USDA 2004 – present Panel Member, site visit Team Member and PGRP-project Advisor, NSF 2000 – present ad hoc reviewer for Genetics, Genome Res, Mol Genet Genomics, Nat Genet, Plant Cell, Plant J, Plant Physiol, PLoS Biol, PNAS, NSF, USDA, DOE 2000 – present Member, American Association for the Advancement of Science, American Society of Plant Biology, Genetics Society of America Teaching Experience Molecular Techniques in Plant Science, Cold Spring Harbor Laboratory. I co-organized this three week course in plant molecular biology and genomics techniques (summer). Light Signal Transduction in Plants, BIOPL4829, Dept. of Plant Biology, Cornell University. I teach a four week module on light signaling for graduate students and senior undergraduates (spring term). Advanced Plant Genetics, PLBR 6060, Dept. of Plant Breeding, Cornell University. I teach two classes on plant transposable elements in this graduate level course in plant genetics (spring term). Methods of Plant Breeding, PLBR 4060, Dept. of Plant Breeding, Cornell University, I organize a half-day lab on maize genetics (fall term). Collaborators and Other Affiliations: (i) Collaborators: Sharon Regan (Queen’s Univ.) Volker Brendel (Iowa State Univ.) Torbert Rocheford (Purdue Univ.) Richard Bruskiewich (IRRI) Tom Ruff (Monsanto) Edward Buckler (Cornell Univ./USDA) Jocelyn Rose (Cornell University) Thomas Clemente (Univ. of Nebraska) Neil Schultes (Conn. Ag. Exp. Station) Dean DellaPenna (Michigan State Univ.) John Sheehy (IRRI) Jon Duvick (Iowa State Univ.) Ann Stapelton (NCSU) Mike Edgerton (Monsanto) David Stern (Boyce Thompson Inst.) Ajay Garg (Cornell Univ.) Qi Sun (Cornell University) Martin Gent (Conn. Ag. Exp. Station) Matthew Terry (Univ. of Southampton, UK) Julian Hibberd (Univ. of Cambridge) Robert Turgeon (Cornell Univ.) Steve Huber (Purdue Univ.) Klaas van Wijk (Cornell Univ.) Matthew Hudson (Univ. of Illinois) Rick Vierstra (Univ. of Wisconsin) C. Neil Hunter (Sheffield Univ.) Erik Vollbrecht (Iowa State Univ.) Pankaj Jaiswal (Oregon State Univ.) Hiayang Wang (Boyce Thompson Inst.) Steve Kresovich (Cornell Univ.) Susan Wessler (Univ. of Georgia) Peng Liu (Iowa State Univ.) Mark Williams (Dupont) Mike Muszynski (Iowa State Univ.) Elli Wurtzel (Lehman College) Chris Myers (Cornell Univ.) Israel Zelitch (Conn. Ag. Exp. Station) Tim Nelson (Yale University) Xinguang Xu (MPI, Shanghai) Richard Peterson (Conn. Ag. Exp. Station) (ii) Graduate and Postdoctoral Advisors: Stephen Dellaporta (Yale University), Jane Langdale (Univ. of Oxford)(iii) Thesis Advisor (7): Ling Bai, Liza Conrad, Sarah Covshoff, Patrice Dubois, Jake Mace, Nicole Hanley Markelz, Moira Sheehan (all Cornell University) Postgraduate-Scholar Sponsor (8): Denise Costich, Tesfamichael Kebrom, Judith Kolkman, Kazuhiro Kikuchi, Pinghua Li, Anasuya Mohapatra, Ruairidh Sawers, Manjit Singh, (all Boyce Thompson Inst.) Richard Bruskiewich [email protected] Professional Preparation: University of British Columbia University of British Columbia Simon Fraser University, BC Medical Genetics Biochemistry, Molecular Biology & Genetics Option General Studies (Minor Computing) Ph.D. 1999 B.Sc. with honours 1992 B.A. 1987 Appointments: Senior Scientist International Rice Research Institute (IRRI) Sept. 2000 – present Adjunct Professor University of the Philippines 2001- present Postdoctoral Research Fellow Sanger Centre, UK 1999 - 2000 Related Publications: Koji Doi, Aeni Hosaka, Toshifumi Nagata, Kouji Satoh, Kohji Suzuki, Ramil Mauleon, Michael J Mendoza, Richard Bruskiewich and Shoshi Kikuchi. (2008) Development of a novel data mining tool to find cis-elements in rice gene promoter regions. BMC Plant Biology 2008, 8:20. doi:10.1186/1471-2229-8-20 (http://www.biomedcentral.com/1471-2229/8/20) Richard Bruskiewich, et al. 2008. “The Generation Challenge Programme Platform: Semantic Standards and Workbench for Crop Science,” International Journal of Plant Genomics, vol. 2008, Article ID 369601, 6 pages. doi:10.1155/2008/369601 Rice Annotation Project (2007) The Rice Annotation Project Database (RAP-DB): 2008 update. Nucleic Acids Research, doi:10.1093/nar/gkm978 Samart Wanchana, Supat Thongjuea, Victor Jun Ulat, Mylah Anacleto, Ramil Mauleon, Mathieu Conte, Matthieu Rouard, Manuel Ruiz, Nandini Krishnamurthy, Kimmen, Theo van Hintum and Richard M. Bruskiewich (2007) The Generation Challenge Programme Comparative Plant Stress-Responsive Gene Catalogue. Nucleic Acids Research, doi:10.1093/nar/gkm798 Takeshi Itoh, Tsuyoshi Tanaka, Roberto A. Barrero, Chisato Yamasaki, Yasuyuki Fujii, Phillip B. Hilton, Baltazar A. Antonio, Hideo Aono, Rolf Apweiler, Richard Bruskiewich, et al. 2007. Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana. 2007. Genome Res. 17:175-183 Significant Publications: Richard Bruskiewich, Guy Davenport, Tom Hazekamp, Thomas Metz, Manuel Ruiz, Reinhard Simon, Masaru Takeya, Jennifer Lee, Martin Senger, Graham McLaren, and Theo Van Hintum. 2006. The Generation Challenge Programme (GCP)-Standards for Crop Data. OMICS 10(2):215-219 Kenneth L. McNally, Richard Bruskiewich, David Mackill, C. Robin Buell, Jan E. Leach, and Hei Leung. 2006. Sequencing Multiple and Diverse Rice Varieties. Connecting WholeGenome Variation with Phenotypes. Plant Phys. 141:1–6 McLaren, CG; Bruskiewich, RM; Portugal, AM; Cosico, AB. 2005. The International Rice Information System. a platform for meta-analysis of rice crop data. Plant Physio. 139 (2): 637-642 International Rice Genome Sequencing Project, 2005. The map-based sequence of the rice genome. Nature 436, 793-800. Richard Bruskiewich and Samart Wanchana S. 2007. C4 rice: brainstorming from bioinformaticians. in Charting new pathways to C4 rice, ed. by J. E. Sheehy, P. L. Mitchell and B. Hardy, p. 381-398, ill. Ref. Los Banos, Laguna: IRRI. Synergistic Activities: Scientific Service: Sept. 2000 – present Senior Scientist, Computational and Systems Biology; IRRI Frontier Project & Consortium for C4 Rice Photosynthesis. Duties: Leading the IRRI-based bioinformatics and systems biology team developing and applying computational tools and methodology to store, analyze, integrate and interpret project data within the Bill and Melinda Gates Foundation funded IRRI Frontier Project and Consortium for C4 Rice Photosynthesis. 1999 - 2000 Postdoctoral Research Fellow, Human Analysis Group, Sanger Centre, Welcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom. Duties: assessment of the sensitivity and specificity of ab initio gene prediction algorithms; whole genome annotation and visualization of the first completed human chromosome, 22 (published in Nature, December 1999); whole genome analysis and visualization of Single Nucleotide Polymorphisms in human chromosome 22 (i) Collaborators: Apweiler, Rolf (European Bioformatics Inst.) Brutnell, Thomas (Boyce Thompson Inst) Buell, C. Robin (Michigan State Univ.) Doi, Koji (National Inst. Of Agrobio. Sciences) Gent, Martin (Conn. Ag. Exp. Station) Hazekamp, Tom (IPGRI) Hosaka, Aeni (National Inst. Of Agrobio. Sciences) Jaiswal, Pankaj (Oregon State Univ.) Jun Ulat, Victor (IRIS) Khush, Gurdev (IRRI) Kikuchi, Shoshi (National Inst. Of Agrobio. Sciences) Krishnamurthy, Nandini (Univ. of California) Leung, Hei (IRRI) Mackill, David (IRRI) Madamba, Ma (IRRI) Yamazaki, Yukiko (National Institute of Genetics) Yap, Immanuel (Cornell Univ.) Zhu, Xinguang (MPI, Shanghai) Mauleon, Ramil (IRRI)McLaren, Graham (IRRI) Mendoza, Michael (IRRI) Mertz, Thomas (IRRI) Myers, Chris (Cornell University) Nagata, Toshifumi (National Inst. Of Agrobio. Sciences) Portugal, Arlett (IRRI) Ramos-Pamplona, Marilou Rouard, Mathieu (CGAR) Ruiz, Manuel (CIRAD) Satoh, Kouji (National Inst. Of Agrobio. Sciences) Sjolander, Kimmen (Univ. of California) Suzuki, Kohji (Hitachi Software Engineering) Van Hintum, Theo (Centre for Genetic Resources) Wanchana, Samart (IRRI) Wang, Guoliang (Ohio State Univ.) Martin Paul Neville Gent [email protected] Professional preparation: Oberlin College Yale University University of Pittsburgh Appointments: Agricultural Scientist Associate Scientist Assistant Scientist Chemistry Physical Chemistry Life Sciences Connecticut Agricultural Experiment Station Connecticut Agricultural Experiment Station Connecticut Agricultural Experiment Station B.A., with Honors 1971 Ph.D. 1975 1975 - 1978 Oct 2003 - present Oct 1989 - Oct 2003 April 1978 - Oct 1989 Related publications: Gent, M.P.N. 2008. Effect of Shade on Water and Nutrient Use in Greenhouse Tomato. J. Amer. Soc. Hort. Sci. 133:619-627. Gent, M.P.N., J.C. White, B.D. Eitzer, M.J.I. Mattina. 2007. Modeling the Difference among Cucurbita in Uptake and Translocation of p,p'-dichlorophenyl-1,1-dichloroethylene. Environ. Toxicol. Chem. 26:2476-2485. Gent, M.P.N. 2006. Modeling the Effect of Nutrient Solution Composition and Irradiance on Accumulation of Nitrate in Hydroponic Lettuce. Acta Horticulturae 718:469-476. Gent, M.P.N. 2005. Effect of genotype, fertilization, and season on free amino acids in leaves of salad greens grown in high tunnels. J Plant Nutrition 28:1-14. Gent, M.P.N. 2003. Effect of conductivity and nitrate supply ratio on nitrate accumulation in hydroponic lettuce. HortScience 38:222-227. Significant publications: Gent, M.P.N., J.C. White, Z.D. Parrish, M. Iseleyen, B.D. Eitzer, M.J.I. Mattina. 2007. Uptake and Translocation of p,p’-dichlorodiphenyldichloroethylene supplied in Hydroponics Solution to Cucurbita. Environ. Toxicol. Chem. 26:2467-2475. Gent, M.P.N. 2007. Effect of Degree and Duration of Shade on Quality of Greenhouse Tomato. HortScience 42:514-520. Gent, M.P.N. 2004. Efficacy and persistence of paclobutrazol applied to rooted cuttings of rhododendron before transplant. HortScience 39:105-109. Gent, M.P.N. 2002. Modelling Intra-cellular control of nitrate and long distance transport in plants. Acta Horticulturae 593:93-99. Gent, M.P.N., Y-Z Ma. 2000. Growth and mineral nutrition of tomato seedlings under diurnal temperature variation of the root and shoot. Crop Science 40:1629-1636. Synergistic activities: Outreach Activities My research is primarily directed to improving commercial production of ornamental and vegetable crops in greenhouses, in particular relating environment and fertilization to production, quality, and value for human nutrition. Outreach consists of visits and collaboration with growers, talks to growers groups, and interaction with Extension Agents 1995 – present Steering ctte New England Vegetable and Fruit Growers Conference 1997 – present Regional Research Ctte Commercial Greenhouse Production 2005 – present USDA SBIR Grant with Geremia Greenhouse, Wallingford CT Scientific Service: 1993-97, 2002-04, 2008-10 Chair, Working group on Plant Biology Amer. Soc. Hort. Sci. 2001 - present Associate editor, J. Plant Nutrition 1985 – present ad hoc reviewer for J. Amer. Soc. Hort. Sci., Hortscience, Acta Hort., Crop Science, Agron. J., Int. J. Phytoremediation 1980 – present member Amer. Soc. Adv. Sci., Amer. Soc. Agronomy, Amer. Soc. Hort. Sci., Int. Soc. Hort. Sci., Amer. Soc. Plant Biology Collaborators and Other Affiliations: (i) collaborators Brutnell, Thomas P. (Boyce Thompson Institute) Burger, William (CT Agric Experiment Station) Eitzer, Brian (CT Agric Experiment Station) Elmer, Wade (CT Agric Experiment Station) Ferandino, Francis (CT Agric Experiment Station) Gage, Daniel (University of Connecticut) Geremia, Joseph (Geremia Greenhouse) Iseleyen, Mohamed (CT Agric Experiment Station) Kiyomoto, Richard (University of Connecticut) Ma, Yong Zhan (Yale University) Mattina, MaryJane (CT Agric Experiment Station) McAvoy, Richard (University of Connecticut) Parrish, Zachia (CT Agric Experiment Station) Smets, Barth (University of Connecticut) Wang, X (CT Agric Experiment Station) Ward, Jeffrey (CT Agric Experiment Station) White, Jason (CT Agric Experiment Station) (ii) Graduate and Postdoctoral advisors: Prestegard, James (University of Georgia); Ho, Chien (Carnegie Mellon University) Pankaj Jaiswal [email protected] Professional Preparation: University of Lucknow, India University of Lucknow, India University of Lucknow, India Botany & Chemistry Biochemistry Botany & Plant Molecular Biology B.Sc 1990 M.Sc 1992 Ph.D. 1998 Appointments 2008-Present Assistant Professor; Dept. of Botany & Plant Pathology, Oregon State University 2007-2008 Sr. Research Associate; Dept. of Plant Breeding & Genetics, Cornell University 2003-2006 Research Associate; Dept. of Plant Breeding & Genetics, Cornell University 2001-2002 Postdoctoral Associate; Dept. of Plant Breeding and Genetics, Cornell University 1999-2000 Postdoctoral Associate; Boyce Thompson Institute at Cornell University 1998–1999 Postdoctoral Associate; Vienna Biocenter, Univ. of Vienna, Austria 1995-1998 Senior Research Fellow, National Botanical Research Institute, Lucknow, India. 1992-1994 Junior Research Fellow, National Botanical Research Institute, Lucknow, India. Five Publications Most Closely Related to the Topic: Liang, C., P. Jaiswal, C. Hebbard, S. Avraham, E. S. Buckler, T. Casstevens, B. Hurwitz, S. McCouch, J. Ni, A. Pujar, D. Ravenscroft, L. Ren, W. Spooner, I. Tecle, J. Thomason, C. W. Tung, X. Wei, I. Yap, K. Youens-Clark, D. Ware and L. Stein (2008). Gramene: a growing plant comparative genomics resource. Nucleic Acids Res. 36(Database issue): D947-53. Epub 2007 Nov 4. Jaiswal P, Ni J, Yap I, Ware D, Spooner W, Youens-Clark K, Ren L, Liang C, Zhao W, Ratnapu K, Faga B, Canaran P, Fogleman M, Hebbard C, Avraham S, Schmidt S, Casstevens TM, Buckler ES, Stein L, McCouch S (2006) Gramene: a bird's eye view of cereal genomes. Nucleic Acids Res. 34: D717-723. Ware DH*, Jaiswal P*, Ni J, Yap IV, Pan X, Clark KY, Teytelman L, Schmidt SC, Zhao W, Chang K, Cartinhour S, Stein LD, McCouch SR. Gramene, a tool for grass genomics. Plant Physiol. 2002; 130(4): 1606-13. (* equal contribution) Ware D, Jaiswal P, Ni J, Pan X, Chang K, Clark K, Teytelman L, Schmidt S, Zhao W, Cartinhour S, McCouch S, Stein L (2002) Gramene: a resource for comparative grass genomics. Nucleic Acids Res 30: 103-105. Gene Ontology Consortium. The Gene Ontology project in 2008." Nucleic Acids Res. 36(Database issue): D440-4. Epub 2007 Nov 4. Five Other Publications: Azevedo, J., F. Courtois, M. A. Hakimi, E. Demarsy, T. Lagrange, J. P. Alcaraz, P. Jaiswal, L. MarechalDrouard and S. Lerbs-Mache (2008). "Intraplastidial trafficking of a phage-type RNA polymerase is mediated by a thylakoid RING-H2 protein." Proc Natl Acad Sci U S A 105(26): 9123-8. Jaiswal P, Avraham S, Ilic K, Kellogg EA, Pujar A, Reiser L, Seung RY, Sachs MM, Schaeffer M, Stein L, Stevens P, Vincent L, Ware D, Zapata F (2005) Plant Ontology (PO): A controlled vocabulary of plant structures and growth stages. Comparative and Functional Genomics 6: 388-397 Pujar A, Jaiswal P, Kellogg EA, Ilic K, Vincent L, Avraham S, Stevens P, Zapata F, Reiser L, Rhee SY, Sachs MM, Schaeffer M, Stein L, Ware D, McCouch S (2006) Whole-plant growth stage ontology for angiosperms and its application in plant biology. Plant Physiol. 142: 414-428. Gene Ontology Consortium, The Gene Ontology (GO) Project in 2006. Nucleic Acids Research. 2006 Jan 1;34:D322-6 Beardslee TA, Roy-Chowdhury S, Jaiswal P, Buhot L, Lerbs-Mache S, Stern DB, Allison LA. A nucleus encoded maize protein with sigma factor activity accumulates in mitochondria and chloroplasts. Plant J. 2002; 31(2): 199-209 Synergistic Activities: 1. Co-PI on the NSF funded Gramene database project on Plant Comparative genomics (2007-2011; DBI# 0703908). Co-PI on the NSF funded Plant Ontology Consortium grant (2003-2006; DBI# 0321666). Co-organizer for Ontologies for Biological Databases workshop at Plant and Animal genome meetings (2004-2008), Plant Ontology workshops at ASPB-Plant Biology meeting (2004, 2007) and Ontology workshops at Cornell University (2006) and Cold Spring Harbor Laboratory Biographical sketch, Pankaj Jaiswal Page 1 (2007). I am the Gramene project’s developer and coordinator for cereal specific pathway databases. I also lead the development of Plant Ontology and contribute the cereal plant specific intellectual inputs to Gene Ontology Project (2001-present). 2. Teaching Plant Physiology, BOT331, Dept. of Botany & Plant Path, Oregon State Univ. (2009) 3. Served as adhoc reviewer for various NSF and USDA grant proposals, book chapters. several scientific journals that include, Science, Bioinformatics, Genetics, Plant Physiology, Plant Molecular Biology, Molecular Genetics and Genomics, Genome Biology, BioMed Central, Plant Cell Physiology, Journal of Plant Biochemistry and Biotechnology and Physiology and Molecular Biology of Plants. 4. Advisor: Generation Challenge Programme, Subprog. 4, Domain Modeling & Ontology task (2007present) Conflict of Interest: (i) Collaborators & Other Affiliations: Allison, Lori A. (University of Nebraska-Lincoln) Avraham, Shulamit (CSHL) Beardslee, Thomas A. (Univ of Nebraska-Lincoln) Buhot, Laurence (Université Joseph Fourier) Brutnell, Thomas, P. (Boyce Thompson Inst.) Canaran, Payan (CSHL) Cartinhour, Samuel (USDA-ARS) Casstevens, Terry M. (Cornell Univ.) Chang, Kuan (CSHL, WUSTL) Clark, Kenneth (CSHL) Faga, Benjamin (CSHL) Ilic, Katica (TAIR, Stanford Univ.) Lerbs-Mache, Silva (Université Joseph Fourier) Ni, Junjian (Cornell Univ. ) Pan, Xiaokang (CSHL, Iowa State Univ.) Pujar, Anuradha (Cornell Univ.) Ratnapu, Kiran (CSHL) Ravenscroft, Dean (Cornell Univ.) Reiser, Leonore (TAIR, Stanford Univ.) Ren, Liya (CSHL) Roy-Chowdhury, Sanchita (University of Nebraska-Lincoln) Sachs, Martin M. (USDA-ARS) Schaeffer, Mary (USDA-ARS) Schmidt, Steve (CSHL) Stevens, Peter (Missouri Botanical Garden) Teytelman, Leonid (CSHL, UC Berkley) Tung, Chih-wei (Cornell Univ.) Vincent, Leszek (Univ. of Missouri, Colombia) Yap, Immanuel (Cornell Univ.) Zapata, Felipe (Missouri Botanical Gardens) Zhao, Wei (CSHL) Itoh, Takeshi (AFFRC, Japan) Mishler, Brent (UC Berkley) Nelson, Tim (Yale Univ.) Sasaki, Takuji (AFFRC, Japan) Ashburner, Michael (Cambridge Univ. UK) Blake, Judith (Jackson Lab) Bruskiewich, Richard (IRRI, Philippines) Cherry, Mike (Stanford Univ.) Harris, Midori (EBI, UK) Lewis, Suzanna (LBL-UC Berkley) Yamazaki, Yukiko (NIG-Japan) McCouch, Susan R. (Cornell Univ. ) Buckler, Ed (Cornell Univ. ) Kellogg, Elizabeth A (Univ. of Missouri, St. Louis) Rhee, Seung Y. (TAIR, Stanford Univ.) Stein, Lincoln (CSHL) Ware, Doreen (CSHL, USDA-ARS) Sane, Prafullachandra V. (NBRI, India) (ii) Graduate and Postdoctoral Advisors: Silva Lerbs-Mache, Univ; Joseph Fourier, Susan McCouch, Cornell; Naresh K Mehrotra, Lucknow Univ Lucknow, India; P Nath, NBRI, Sirish A Ranade, NBRI, India; Aniruddha P Sane, NBRI, India; Prafullachandra V Sane, NBRI, India; Rudolf Schweyen, Vienna Biocenter, Vienna; David Stern, Boyce Thompson Inst. (iii) Thesis Advisor and Postgraduate-Scholar Sponsor: Justin Elser (Oregon State Univ.) Biographical sketch, Pankaj Jaiswal Page 2 Shaoying Lu [email protected] Professional Preparation: Tsinghua University, China Applied Mathematics Tsinghua University, China Applied Mathematics University of California, San Diego Computational Mathematics Appointments: Research Assistant Professor Postdoctoral Researcher B.S., 1995 M.S., 1997 Ph.D., 2004 University of Illinois, Urbana-Champaign University of California, San Diego 2005–present 2004-2005 Related Publications: Shaoying Lu, Michailova A, Saucerman J, Cheng Y, Yu Z, Kaiser T, Li W, Bank RE, Holst M, McCammon JA, Hayashi T, Hoshijima M, Arzberger P, McCulloch AD, Multi-scale modeling in rodent ventricular myocytes: Contributions of structural and functional heterogeneities to excitationcontraction coupling. IEEE EMB (2009, in press). Eichorst JP, Shaoying Lu*, Xu J, Wang Y, Differential RhoA dynamics in migratory and stationary cells measured by FRET and automated image analysis. PLoS ONE (2009), 3(12):e4082 (*Equal contribution author). Shaoying Lu, Seong J, Ouyang M, Zhang J, Chien S, Wang Y, The Spatiotemporal Pattern of Src Activation at Lipid Rafts Revealed by Diffusion-Corrected FRET Imaging, PLOS Computational Biology (2008), 4(7):e1000127. Bank RE and Shaoying Lu, A domain decomposition solver for a parallel adaptive meshing paradigm. SIAM J. Sci. Comput. 26 (2004), no. 1, 105--127. Significant Publications: Seong J, Lu S, Ouyang M, Huang H, Zhang J, Frame MC, Wang Y, Visualization of Src activity at different compartments of the plasma membrane by FRET imaging. Chemistry and Biology (2009), 16(1):48-57. Kim TJ, Seong J, Ouyang M, Sun J, Lu S, Hong JP, Wang N, Wang Y, Substrate rigidity regulated Ca2+ oscillation via RhoA pathway in stem cells. J Cell Physiol, (2009), 218(2):285--93. Ouyang M, Shaoying Lu, Li XY, Xu J, Seong J, Giepmans BN, Shyy JY, Weiss SJ, Wang Y. Visualization of Polarized MT1-MMP activity in live cells by FRET Imaging. Journal of Biological Chemistry (2008), 283(25):177740-8. Wang Y, Shaoying Lu, The Application of FRET Biosensors to Visualize Src Activation, Proceedings of SPIE (2008), vol. 6868 (68680A):1-9. Synergistic Activities: Teaching Experience • 03/99 - 06/01 Teaching Assistant, University of California, San Diego. Courses: Pre-Calculus, Calculus, Linear Algebra, Introduction to Partial Differential Equations, Introduction to Applied Statistics, Scientific Computing. • 09/97 - 01/99 Graduate Student Instructor, University of Michigan, Ann Arbor. Courses: PreCalculus, Calculus. Duties include independent teaching of the course for a small class of thirty students, writing syllabus and exams. • 09/95 - 07/97 Teaching Assistant, Tsinghua University. Courses: Numerical Analysis. Invited Speeches • Computational Analysis for Live-cell FRET Imaging, UIUC Digital Signal Processing Seminar, 2008. • Scalable Parallel Algebraic Multgrid Methods, SIAM Conference on Parallel Processing for Scientific Computing, San Francisco, CA, 2004. Collaborators and other Affiliations: (i) Collaborators: Peter W. Arzberger (NPACI) Thomas Brutnell (Boyce Thompson Inst.) Richard Bruskiewich (IRRI) Shu Chien (Univ. of California) Margaret C. Frame (Univ. of Glasgow, UK) Ben N. Giepmans (Groningen Univ., NL) Martin Gent (Conn. Ag. Exp. Station) Anushka Michailova (Univ. of California) Andrew J. McCammon (Univ. of California) Chris Myers (Cornell Univeristy) Jeffrey J. Saucerman (Univ. of Virginia) John Y. Shyy (Univ. of California) Jing Zhang (Johns Hopkins University) Yingxiao Wang (Univ. of Illinois) Stephen J. Weiss (Univ. of Michigan) Xinguang Zhu (MPI, Shanghai) (ii)Graduate and Postdoctoral Advisors: Randolph E. Bank (Univ. of California), Michael J. Holst (Univ. of California), Andrew D. McCulloch (Univ. of California). Christopher R. Myers [email protected] Professional preparation: Yale University Cornell University History Physics B.A., cum laude 1984 M.S. 1988, Ph.D. 1991 Appointments: Senior Research Associate Associate Director Senior Scientist Group Leader Research Associate NSF/CISE Research Associate Postdoctoral Researcher Cornell University Cornell University Beam Technologies, Inc. Cornell University Cornell University Cornell University UC-Santa Barbara 1998-present 2006-2007 1997 1994-1997 1993-1997 1993-1995 1991-1993 Related Publications: R.N. Gutenkunst, J.J. Waterfall, F.P. Casey, K.S. Brown, C.R. Myers, and J.P. Sethna, “Universally sloppy parameters sensitivities in systems biology biology is sloppy”, PLoS Computational Biology 3(10), e189 (2007). B.C. Daniels, Y.-J. Chen, J.P. Sethna, R.N. Gutenkunst, and C.R. Myers, “Sloppiness, robustness, and evolvability in systems biology”, Current Opinion in Biotechnology 19(4), 389-395 (2008). A.O. Ferreira, C.R. Myers, J.S. Gordon, G.B. Martin, M. Vencato, A. Collmer, M.D. Wehling, J.R. Alfano, G. Moreno-Hagelsieb, W.F. Lamboy, G. DeClerck, D.J. Schneider, and S.W. Cartinhour, "Wholegenome expression profiling defines the HrpL regulon of Pseudomonas syringae pv. tomato DC3000, allows de novo reconstruction of the Hrp cis element, and identifies novel coregulated genes", Mol. Plant-Microbe Int. 19(11), 1167-1179 (2006). P.A. Bronstein, M.J. Filiatrault, C.R. Myers, M. Rutske, D.J. Schneider, and S.W. Cartinhour, "Global transcriptional responses of Pseudomonas syringae DC3000 to changes in iron bioavailability in vitro", BMC Microbiology 8:209 (2008). B. Swingle, D. Thete, M. Moll, C.R. Myers, D.J. Schneider, and S.W. Cartinhour, "Characterization of the PvdS-regulated promoter motif of Pseudomonas syringae pv. tomato DC3000 reveals regulon members and insights regarding PvdS function in other pseudomonads", Molecular Microbiology 68 (4), 871-889, (2008). Significant Publications: C.R. Myers, “Satisfiability, sequence niches, and molecular codes in cellular signaling”, IET Systems Biology 2(5), 304-312 (2008). C.R. Myers, “Software systems as complex networks: structure, function, and evolvability of software collaboration graphs”, Phys. Rev. E 68, 046116 (2003). K.S. Brown, C.C. Hill, G.A. Calero, C.R. Myers, K.H. Lee, J.P. Sethna, and R.A. Cerione, “The statistical mechanics of complex signaling networks: nerve growth factor signaling”, Physical Biology 1, 184-195 (2004). J.J. Waterfall, F.P. Casey, R.N. Gutenkunst, K.S. Brown, C.R. Myers, P.W. Brouwer, V. Elser and J.P. Sethna, "The sloppy model universality class and the Vandermonde matrix", Phys. Rev. Lett. 97, 150601 (2006). C.R. Myers, R.N. Gutenkunst, and J.P. Sethna, “Python unleashed on systems biology”, Computing in Science and Engineering 9(3), 34-37 (2007). Synergistic Activities: Scientific Service 1993 present Referee for several journals, reviewing papers in physics, biology, computer science, and computational science 1990 present Developer and/or contributor to multiple open source scientific software packages 2008 present Member, External Advisory Board, Complexity Sciences Center, UC-Davis 2008 present Moderator, Molecular Networks section of q-bio e-print arxiv, www.arxiv.org/archive/q-bio Teaching 2004 present Co-developer and co-teacher of interdisciplinary graduate computational laboratory course on Computational Methods for Nonlinear Systems Collaborations and other affiliations (i)Collaborators: James R. Alfano (Nebraska) Philip A. Bronstein (USDA-ARS) Piet Brouwer (Cornell) Kevin S. Brown (Harvard) Thomas Brutnell (BTI) C.Robin Buell (TIGR) Guillermo A. Calero (Cornell) Samuel Cartinhour (USDA-ARS) Fergal P. Casey (Univ. College, Dublin) Richard A. Cerione (Cornell) Alan Collmer (Cornell) Jim P. Crutchfield (UC-Davis) Raissa, M. D’Souza (UC-Davis) Veit Elser (Cornell) Ryan N. Gutenkunst (Cornell) Melaine J. Filiatrault (USDA-ARS) David Guttman (Toronto) Christopher L. Henley (Cornell) Colin C. Hill (GNS, Inc.) Vinina Joardar (TIGR) Kelvin H. Lee (Cornell) Warren Lamboy (USDA-ARS) Magdalen Lindeberg (Cornell) John Mansfield (Imperial College, UK) Gregory Martin (Cornell) Gabriel Moreno-Hagelsieb (Wilfrid Laurier) Tim Nelson (Yale) Michael Rutske (Cornell) Eric Sakk (Morgan State) Lisa Schecter (Missouri-St. Louis) Jakob Schiotz (DTU, Denmark) David J. Schneider (USDA-ARS) James P. Sethna (Cornell) John Sheehy (IRRI) John Stavrinides (Toronto) Paul Stodghill (USDA-ARS) Qi Sun(Cornell) Bryan Swingle (USDA-ARS) Yuhai Tu (IBM) Robert Turgeon (Cornell) Klaas van Wijk (Cornell) Joshua J. Waterfall (Cornell) Misty Wehling (Nebraska) Mingming Wu (Cornell) (ii)Graduate and Postdoctoral Advisors: Ph.D: James P. Sethna (Cornell); Postdoctoral: James S. Langer (UC-Santa Barbara) (iii) Thesis Advisor: Postdocs: Siew Ann Cheong (Nanyang Tech. Univ.) [Four postdoctoral scholars total.] Graduate students: co-supervised with James P. Sethna: Nicholas Bailey (Ph.D in Physics, Cornell), Lance Eastgate (Ph.D. in Physics, Cornell), Joshua J. Waterfall (Ph.D. in Physics, Cornell), Fergal P. Casey (Ph.D. in Applied Mathematics, Cornell), Ryan N. Gutenkunst (Ph.D. in Physics, Cornell). Xinguang Zhu [email protected] Professional Preparation: Shandong Normal University, China Institute of Botany, Chinese Academy of Sciences, China. University of Illinois - Urbana Champaign Biology B.Sc., 1996 Plant Physiology Physiology and Molecular Plant Biology M.Sc., 1999 Appointments: Junior Independent Group Leader, Partner Institute of Computational Biology (MPG/CAS), Research scientist, Department of Plant Biology, Institute of Genomic Biology, University of Illinois at Urbana Champaign, Postdoc research scientist, Plant Biology/UIUC Ph.D., 2004 Aug. 2008-Current Mar. 2006 – Current Aug. 2004-Mar. 2006 Related Publications: Zhu, X-G, Whitmarsh, J., Ort, D.R. and Long, S.P. (2004) Study of the effects of photoinhibition on dynamics of carbon uptake using reverse ray-tracing algorithm. Journal of Experimental Botany 55: 1167-1175. Zhu X-G, Govindjee, Baker, N.R., deSturler, E., and Long, S.P. (2005) Fluorescence in silico: Simulations of chlorophyll a fluorescence induction kinetics of green plants via representation of the complete sequence of excitation energy and electron transport events around photosystem II. Planta 223, 114-133 Long SP, Zhu X-G, Naidu SL, Ort DR (2006) Can improvement in photosynthesis increase crop yields? Plant Cell and Environment 29: 315-330. Zhu, X-G , deSturler, E. and Long, S.P. (2007) Optimized distribution of carbon metabolism enzymes can dramatically increase photosynthetic CO2 uptake rate. - Theoretical explorations using a complete model of photosynthetic carbon metabolism, Plant Physiology, 145: 513-526. Zhu X-G, Long SP, Ort DR (2008) What is the maximum efficiency with which photosynthesis can convert solar energy into biomass? Current Opinion in Biotechnology 19: 153-159. Significant Publications: Zhu, X-G, Portis, A.R. and Long, S.P. (2004) Would transformation of C3 crop plants with foreign Rubisco increase productivity? A computational analysis extrapolating from kinetic properties to canopy photosynthesis. Plant Cell and Environment 27, 155-165. Wittig, W., Bernacchi, C.J., Zhu, X.-G., Gielen, B., Miglietta, F., Angelis, P.D., Ceulemans, R. and Long, S.P. (2005) Modeling gross primary production for Populus spp grown under free-air CO2 enrichment. Global Change Biology, 11, 644-656. Wang Z, Zhu X-G, Chen YZ, Yang J, Li YY, Li YX, Liu L (2006) Exploring photosynthesis evolution by comparative analysis of metabolic network between chloroplast and cyanobacteria. BMC Genomics 7: 100. Wang SW and Zhu X-G. Coupling cyberinfrastructure and GIS to empower ecological and environmental research. Bioscience (2008). Ainsworth EA, et al, Zhu X-G, Curtis PS, Long SP (2002) A meta-analysis of elevated [CO2] effects on soybean (Glycine max) physiology, growth and yield. Global Change Biology 8: 695-709. Synergistic Activities: Scientific Service From 2003: Reviewer for Plant, Cell & Environment, Tree Physiology, Global Change Biology, Photosynthesis Research, Functional Plant Biology, Plant Physiology, New Phytologist, Journal of Photochemistry and Photobiology; Climate Change From 2009: Editorial advisory board: GCB Bioenergy Teaching Experience September 2008 Invited speaker and workshop session leader, Dynamic models of photosynthetic metabolisms – theory and lab. At Plant Systems Modeling Summer School, the Flanders Interuniversity Institute for Biotechnology (VIB), Department of Plant Systems Biology, Ghent, Belgium. April 2008 Organizer, speaker, and session leader, Photosynthesis systems biology research – theory and lab. At Workshop for Bioenergy related Plant Systems Biology Research, Instiute of Computational Biology, Chinese Acadamy of Sciences and Max-Planck Institue, Shanghai, China. Collaborators & Other Affiliations: (i) Collaborators: Baker, Neil R. (Essex Univ., UK) Bernacchi, Carl J. (Water Survey, IL) Cornic, Gabriel. (Uni. Paris) DeLucia, Evan H. (Univ. Illinois) de Sturler, Eric (Virginia Tech) Govindjee (Univ. Illinois) Kramer, David (Washington State Univ.) Li, YiXue (Shanghai Center for Bioinformatics Tech) Liu, Lei (Univ. Illinois) Long, Stephen P. (Univ. Illinois) Mott, Keith (Utah State Univ.) Ort, Donald R. (Univ. Illinois) Portis, Archie R. (Univ. Illinois) Rogers, Alistair (Brookhaven National Laboratory, NY) Sheng, Zhong (Univ. Illinois) Wang, Shaowen (Univ. Illinois) (ii) Graduate and Postdoctoral Advisors: Long, S. P. (Univ. Illinois), Zhang, Q.D. (Institute of Botany, Chinese Academy of Sciences, Retired).(iii) Thesis Advisor, Postdoc (4) Dr. Daniel Tholen (Utrecht University); Dr. FuQiao Xu (Shanghai Institute of Biological Sciences); Dr. GuiLian Zhang (East China Normal University); Dr. Vincent Devloo (University livre de Bruxelles) Graduate (5) Zhuo Wang, Yu Wang, Lisha Zhu, Xiao Chang, HongBo Li
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