Philip E. Bourne, Ph.D. - US grants

The Protein Data Bank (PDB) contains the atomic structure of macromolecules. As of October 1991 there were 790 structural entries (196 Mbytes), if current growth rates persist, this number could grow to 10,000 by the end of the decade. The data provide opportunities for understanding biological function through, for example, comparative structural research. This work addresses several challenges in first making the PDB more accessible to molecular biologists and crystallographers in particular, and second assisting in the management of increasing amounts of data. Several software developments are being undertaken in parallel, but share the same class libraries. First, a new object-based PDB storage format provides suitable access to the levels of substructure found in macromolecules. Second, object-based software tools that interrogate and manipulate structural data, and assist in structure verification are being derived from existing structured programs. Finally, a high-level query language provides intuitive and direct interaction with the PDB. Each aspect of software development proceeds by prototyping followed by iterative cycles of testing in the laboratory and code modification. This work integrates the state-of-art database research results such as object-oriented databases and knowledge bases, software engineering results such as component and glue collaborative work such as extended transaction models to support cooperative scientific research. These tools could potentially precipitate the discovery of new structure-function relationships by permitting data query in a more intuitive fashion.

9310154 Bourne The macromolecular crystallography community has recently adopted a standard set of data definitions as extension to that subset already derived for small molecule crystallography and referred to as the Crystallographic Information File (CIF). Macromolecular CIF definitions will facilitate the highly desireable features of simpler information exchange and a rich controlled vocabulary for use world-wide by scientists in an expanding discipline. Speedy adoption of CIF requires flexible, interoperable, and portable software tools. The investigators will build a class library and a set of tools based on the object-oriented software technology to browse, edit, display, query, verify and format CIF files, called CIFters. In addition, CIFters will be callable from existing programs in common use in macromolecular crystallography facilitating access to CIF files, further promoting the use of CIF. The long term goal of this project is to develop extensible software tools which are widely available to the structural biology community. In addition, this award support an end-user workshop to begin the effort to design the appropriate CIFters. ***

technology /technique development; proteins; nucleic acids; enzymes; computers; biomedical resource;

structural biology; technology /technique development; computers; biotechnology; biomedical resource;

*** Proteins are aptly referred to as nature's building blocks. Understanding how these proteins function is key to understanding life's processes. On the other hand, understanding why these proteins do not function, or function incorrectly, tells us much about particular diseases and illnesses. Therefore, it is not surprising that the amount of experimental data available on proteins, like most other biological data, are growing exponentially as we attempt to unravel these mysteries. Effective use of these data requires usable and current databases. Most public databases contain only one form of data, either sequences, structure, and to a lesser extent functional information, on a large variety of loosely classified proteins. While these resources are clearly very useful, other types of resources are needed that are publicly available yet can be maintained at very low cost. This project encompasses the development of one such database that will contain an automated classification of proteins based on an extensive set of properties more properties than considered by any other resource. The Database of Classified Proteins (DCP) is a generalization of previous work for supporting information specifically on the protein kinase family of enzymes (see http://www. sdsc.edu/kinases). The DCP will contain an extensive set of physical and derived properties (a composite property description) including sequence, structure, evolutionary information (e.g., correlated mutations) and functional sites (initially derived from structure but later predicted from the composite description). New protein structures deposited with the PDB will be, where possible, aligned to an existing composite property description defining a protein family. The outcome of this work will be an all-by-all comparison of proteins for which structures are known derived using the compute resources of the National Partnership for Advanced Computational Infrastructure (NPACI). That comparison wil l be publicly available as the DCP and maintained on a 7/24 basis. The DCP will provide new opportunities for comparing proteins and visualization tools are pro-posed to make this possible through the Web. The DCP should provide new insights into protein function by revealing hitherto undiscovered functional sites. Furthers the DCP should be useful as a fold recognition database for use in threading sequences with unknown structure on to known folds. The DCP will contain much more information than could hitherto be applied to the structure prediction problem. ***

technology /technique; proteins; drug /agent; cardiovascular system; hematology; biomedical resource; biological products;

This project is developing efficient and stable implementations of the AMBER molecular modeling package on parallel machines for use at SDSC. There are two general aspects to the proposed research: a fine-grained implementation of the molecular dynamics and minimization algorithms, followed by a more coarse-grained parallelization of free energy calculations. A new direction in the past year is the parallelization of the particle-mesh Ewald code, along with further improvements in other areas. A major test case involving a 60,000 atom system is in progress. We use the Message Passing Interface (MPI) programming model developed at Argonne Labs for our basic MD implementation. Most vendors, including Intel, IBM, and Cray/SGI now support MPI. We now have (nearly) identical parallel code on clusters of workstations and on MPP machines like the Cray T3E, IBM's SP1 and SP2 machines, and the Convex Exemplar SPP. The MPI implementation is now a standard part of version 5.0 of AMBER, making it available to workers throughout the world. The code development has been a collaborative effort, involving primarily John Vincent and Ken Merz (PSU), Tom Cheatham and Peter Kollman (UCSF), David Case (TSRI), and Jerry Greenberg and Jack Rogers (SDSC). The release of Amber 5.1 is now being prepared and is expected in fall, 1998. This release will be coordinated by D.A. Case. Key parallel improvements that are now in final testing include: * Greatly improved parallel implementation of particle-mesh Ewald code; * Fully parallel implementation of free energy perturbation codes * Parallel implementation of "locally-enhanced sampling", a multiple-copies approach to dynamics * Parallel implementation of NMR restraints for structure refinement Goals for the coming year include: (1) tuning of the communication steps to achieve performance more like that expected on theoretical grounds; (2) additional production calculations (of DNA + salt + water) to test and illustrate the use of the new codes; (3) adapting coarse-grained parallel algorithms for free energy calculations.

Biological systems are integrated complex assemblies of macromolecules that use chemical energy to sustain life. As such, their properties area function of their physicochemical parameters such as solubility, lipophilicity, electronic effects, ionization, and stereochemistry, that have profound influence on the chemistry and biochemistry of the complex.

This project develops a computational platform that integrates 1. physically-based computational and analytical modeling using QM techniques, 2. experimental databases, 3. computational analysis tools, and 4. visualization/manipulation interfaces, in order to create a transparent and common interface for the use of these now relatively disparate set of tools. This infrastructure will provide a database and integrate associated tools that allows the user to focus on the principles of stereochemistry, chemical synthesis, computational structure prediction, and physical analysis as applied to molecular recognition, biomolecular conformational analysis, and supramolecular chemistry. The end result will impact biologists and biochemists working in areas such as bioorganic chemistry, medicinal chemistry, enzyme structure and function, and nucleic acid recognition.

Voltage gated channels are one of the ways that materials move into and out of cells. They are important across biology. A channel can either be open or closed; the transition is called gating. However, these proteins do not crystallize easily and two-dimensional methods have had to be developed to consider their structure. Each channel protein consists of six hydrophobic membrane-spanning segments and a membrane insertion region.

The ability to predict or at least have good models for these transmembrane proteins is a significant need for the research community. The techniques for this are now just beginning. At the moment, there are no good homologues to VGC proteins in the PDB, because of the difficulty of crystallization. However, alignment of sequence is possible. Three-dimensional protein homology models will be developed from these aligned sequences, using a variety of software packages developed by the group. The resulting tools will be available on the web. Once the first models are made, all similarly aligned proteins can be automatically predicted. This effort will produce models that could be used to refine the structure data coming from new studies and methods of considering membrane proteins.

Protein mutation occurs as part of the evolutionary process, through mutagenesis and through post-translational modification. As yet no resource has been developed that permits the systematic study of the effect of all these mutations on protein structure, and hence function, even though the literature is full of individual instances. The new resource will contain all relevant PDB structures as its starting point and will be updated along with PDB. A prototype has been established at http://pmr.sdsc.edu. The production resource will bring together sequence, structure, and literature information using novel information acquisition tools and provide query and visualization tools for global analysis of the effects of mutation. Research in protein structure and engineering will be enhanced through using the resource for prediction and for confirmation of methods. The resource will be accessible through the web and other users may write software for doing direct querying of the resource.

This is the era of biology, and at this moment in time, structural biology as manifest in the various structural genomics project under way worldwide. With protein structures at center stage comes the need for further structure characterization, more informed decisions about which new structures to determine, and the need for new tools to associate structure with function. This group, who through the PI, are already entrusted with the query and distribution of all structure data as deposited with the Protein Data Bank (PDB), propose a new community service to enable the science of structure genomics. The service will provide and new algorithms, associated software tools, and data (collectively referred to as the resource) to facilitate the process of high throughput structure determination and the interpretation of that large body of new structure data in a semi-automated process. Specifically the resource will: (i) facilitate structure genomics by guiding target selection towards new folds and/or biological function; (ii) provide functional annotation to newly determine structures of unknown function; and (iii) provide a comprehensive database of comparative (homology) models. The proposal brings together researchers from the University of California San Diego (UCSD), The Burnham Institute (TBI) and The Keck Graduate Institute (KGI) who will provide a public Web-accessible computing resource with associated software and data for use by all of the structural genomics community. The resource will be located at the San Diego Supercomputer Center (SDSC) which has a record of delivery high quality services to the biology community. The proposed public resource will complement the private software and data resulting from the individual structural genomics centers as they undertake competitive high throughput structure determination.

This collaborative project aims to establish a national computational resource to move the research community much closer to the realization of the goal of the Tree of Life initiative, namely, to reconstruct the evolutionary history of all organisms. This goal is the computational Grand Challenge of evolutionary biology. Current methods are limited to problems several orders of magnitude smaller, and they fail to provide sufficient accuracy at the high end of their range.

The planned resource will be designed as an incubator to promote the development of new ideas for this enormously challenging computational task; it will create a forum for experimentalists, computational biologists, and computer scientists to share data, compare methods, and analyze results, thereby speeding up tool development while also sustaining current biological research projects.

The resource will be composed of a large computational platform, a collection of interoperable high-performance software for phylogenetic analysis, and a large database of datasets, both real and simulated, and their analyses; it will be accessible through any Web browser by developers, researchers, and educators. The software, freely available in source form, will be usable on scales varying from laptops to high-performance, Grid-enabled, compute engines such as this project's platform, and will be packaged to be compatible with current popular tools. In order to build this resource, this collaborative project will support research programs in phyloinformatics (databases to store multilevel data with detailed annotations and to support complex, tree-oriented queries), in optimization algorithms, Bayesian inference, and symbolic manipulation for phylogeny reconstruction, and in simulation of branching evolution at the genomic level, all within the context of a virtual collaborative center.

Biology, and phylogeny in particular, have been almost completely redefined by modern information technology, both in terms of data acquisition and in terms of analysis. Phylogeneticists have formulated specific models and questions that can now be addressed using recent advances in database technology and optimization algorithms. The time is thus exactly right for a close collaboration of biologists and computer scientists to address the IT issues in phylogenetics, many of which call for novel approaches, due to a combination of combinatorial difficulty and overall scale. The project research team includes computer scientists working in databases, algorithm design, algorithm engineering, and high-performance computing, evolutionary biologists and systematists, bioinformaticians, and biostatisticians, with a history of successful collaboration and a record of fundamental contributions, to provide the required breadth and depth.

This project will bring together researchers from many areas and foster new types of collaborations and new styles of research in computational biology; moreover, the interaction of algorithms, databases, modeling, and biology will give new impetus and new directions in each area. It will help create the computational infrastructure that the research community will use over the next decades, as more whole genomes are sequenced and enough data are collected to attempt the inference of the Tree of Life. The project will help evolutionary biologists understand the mechanisms of evolution, the relationships among evolution, structure, and function of biomolecules, and a host of other research problems in biology, eventually leading to major progress in ecology, pharmaceutics, forensics, and security.

The project will publicize evolution, genomics, and bioinformatics through informal education programs at museum partners of the collaborating institutions. It also will motivate high-school students and college undergraduates to pursue careers in bioinformatics. The project provides an extraordinary opportunity to train students, both undergraduate and graduate, as well as postdoctoral researchers, in one of the most exciting interdisciplinary areas in science. The collaborating institutions serve a large number of underrepresented groups and are committed to increasing their participation in research.

The University of California at San Diego has been granted an award to facilitate student and young scientist participation in the Intelligent Systems for Molecular Biology (ISMB) conference in Glasgow Scotland in July of 2004. The conference provides a generalforum for disseminating the latest developments in bioinformatics and other computational aspects of molecular biology. The conference is annual and alternates between North America and non-North American sites. The 2004 conference will be held as a joint conference with the 2004 European Conference on Computational Biology (ECCB). The combined goal of the ISMB and ECCB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting that will be of major benefit to those who will be enabled to attend by this award.

DESCRIPTION (provided by applicant): The Intelligent Systems for Molecular Biology (ISMB) conference provides a general forum for disseminating the latest developments in bioinformatics. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The venue for the ISMB meeting moves annually between North America and non North American sites. The dates for ISMB 2005 is June 25 - 29, 2005, and will be held in Detroit, Ml, USA. ISMB 2006 will be held in Fortaleza, BRAZIL on August 06-10, 2006. The ISMB 2007 site is yet to be determined. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting. This grant requests funding in support of student participation and student related costs. In a highly international and interdisciplinary field such as computational biology, it is important for students to gain experience with a variety of approaches and viewpoints. Students will have ample opportunity, in many cases for the first time, to present their work as posters or as formal presentations. The contacts that they form and the directions they choose may last their professional lives. It has been the experience of ISMB conferences in the past that the high number of student and young investigator participants (approximately 37% of all participants) gives the conference a unique vitality and energy. This proposal seeks to assist them at this critical but resource-limited stage in their careers.

The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 12 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The venue for the ISMB meeting usually alternates between North American and non North American sites. ISMB 2005 will be held in Detroit, Michigan. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on "intelligent systems" and actual biological data makes ISMB a unique and highly important meeting, and 12 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference.
This grant request is for funding for student, young scientist, and presenter travel and expense to attend the Intelligent Systems for Molecular Biology conference. In a highly international and interdisciplinary field such as computational biology, it is important for students to gain experience with a variety of approaches and viewpoints. From the Tutorial program, which provides an excellent way for students and senior researchers to quickly come up to speed in new areas, through to the final keynote address, students will have ample opportunity, in many cases for the first time, to present their work as posters or as formal presentations and meet with fellow researchers from other institutions around the globe. The contacts that they form and the directions they choose may last their professional lives. This proposal seeks to assist them at this critical but resource-limited stage in their careers.

The Intelligent Systems for Molecular Biology (ISMB) conference is the annual meeting of the International Society for Computational Biology (ISCB). The ISMB conference has provided an annual forum for disseminating the latest developments in bioinformatics since 1993, thus serving as a key vehicle for achievement of the Society's mission. Past ISMB conferences have drawn attendees from as many as 38 countries, and up to 2136 attendees. Since 2000 the conference location has been purposefully alternated between North America, Europe, and non-North American/non-European sites to foster international exchange and collaboration. ISMB 2006 is being held in Fortaleza, Brazil, August 6-10, 2006.
As a multidisciplinary conference rich in diversity, ISMB brings together students, researchers, faculty, and staff, all of whom share a focus on computer science, molecular biology, biology, mathematics and/or statistics. ISMB focuses on research centered on actual biological problems rather than simply theoretical calculations, and attendees effectively discuss and distribute the latest developments in "intelligent systems for molecular biology." Intelligent systems include any software which goes beyond straightforward, closed-form algorithms or standard database technologies, and encompasses those that view data in a symbolic fashion, learn from examples, consolidate multiple levels of abstraction, or synthesize results to be cognitively tractable to a human, including the development and application of advanced computational methods for biological problems.
This award provides funding to assist students and junior researchers in attending ISMB 2006. The knowledge gained and the contacts made will have an important impact downstream on the state of computational biology in the US, particularly in forging new ties with our Latin and South American partners.

The University of California at San Diego is awarded a grant to develop tools for integrating biological literature and databases. Changes in the scientific publishing industry blur the distinction between biological databases and the biological literature and it is the time to capitalize on this hitherto unappreciated similarity. Tools will be developed to provide seamless integration between the knowledge and data traditionally held within biological journals with the related information, which is traditionally held within biological databases. The open source software tools are collectively called BioLit and will facilitate this integration and provide a broad community with the potential to achieve a new level of efficient comprehension of the products of the scientific endeavor. Initially, BioLit will comprise authoring tools to facilitate biologists in employing existing ontologies, post manuscript submission tools to extract relevant facts from the manuscript which are stored as metadata, a database of journal content and tools for the visualization and further analysis of data and knowledge presented in this database of on-line published papers. BioLit development and testing will be performed in a unique environment consisting of the complete corpus of Public Library of Science (PLoS) journals integrated with the Protein Data Bank (PDB), one of the oldest and most used databases in all biology. In the third year of the project an evaluation of the tools will be performed as will a survey of how useful the community regards what has been achieved in this initial phase.

Under a special agreement with the University of California tools from this effort will be open source and distributed through sourceforge.net and hence available to any publisher or database provider who cares to employ them. The broader impacts resulting from the proposed activity comes from, first, the application of the tools and principles defined herein to any field of science. Second, and most important, the proposal brings the promise to the scientific consumer of a new and powerful medium from which to learn. A medium that retains all of the intellectual merits of high quality scientific journals, achieved through peer review and high quality editing, yet adds direct access to the data upon which conclusions are reached. Conversely, access through biological databases provided transversal from a data point to the conclusions reached in the literature about that item of data. A positive evaluation of the integrative approach enabled by the tools proposed here could have a far-reaching impact on the means by which science is disseminated and consumed.

This is a project to engage students and teachers with the rapidly expanding science content available using information technology and through the cyberinfrastructure. Learners seldom have an opportunity to also be contributors, and underserved and disadvantaged students are most often bypassed for such opportunities. The project uses methods that the PI believes inspire student involvement and learning, engage teachers, and meet district/state/national standards.

The partners include Sweetwater Unified High School District, the University of California at San Diego, San Diego State University, and a number of local IT firms and others. The workshops are interdisciplinary and include 25-30 teachers each summer (three-year total of 75 teachers) from science, math and English classrooms working with "scientists renowned for interdisciplinary science collaboration, and pedagogy experts." In addition, 200 students are involved each summer helping to develop activities and acquiring media, communication and leadership skills.

The activities include student and teacher teams designing and developing "STEMtube clips (in Spanish and English), short videos that document/demonstrate science concepts, career options or explicate scientific journal articles."

DESCRIPTION (provided by applicant): The broad objective of this proposal is to establish a computational platform to predict and understand protein functions at multi-scales, from molecule to cell, through integrating data from structural genomics, functional genomics and chemical genomics, and using tools derived from bioinformatics, chemical informatics and biophysics. There is a serious need to meet this objective in an era of proteomics where proteins are easily isolated, yet not so easily functionally classified with any degree of confidence. As the first step we propose here to: (1) design and implement scalable, accurate, reliable and robust algorithms and associated software for predicting, comparing, searching, and classifying protein functional sites and proteinligand interactions;(2) design and implement an ontology-driven protein functional site and protein-ligand interaction database that integrates comprehensive structure, function, and mutation information and supports quantitative modeling of protein structure and functions at the genome scale;(3) Establish first an intuitive graphical user interfaces (GUI) for scientists to visualize, analyze and mine functional site information for comparative proteomics and second establish an application programming interface (API) for programmers to develop new algorithms and applications using the foundation proposed here. The results of this effort will be disseminated through the Protein Data Bank which is used by over 10,000 scientists every day.

SciTube.tv. is a project to provide a new venue for the dissemination and sharing of scientific information. Initially, in collaboration with the Public Library of Science (PLoS; www.plos.org), SciTube.tv is providing a Web resource for authors to upload a video clip linked with a paper published in a PLoS journal. The video clip will include a voice commentary, a pictorial stream of the presenter, a PowerPoint presentation, as well as links between the video presentation and the journal article. SciTube.tv presentations provide an intermediate level of detail between a typical abstract of a scientific paper and the full paper. SciTube.tv will appeal particulary to the new generation of scientists conversant with the video technologies prevalent in today's popular culture. The technical aspects for this resource are being provided by the San Diego Supercomputer Center (SDSC; www.sdsc.edu) by way of their Cyberinfrastructure Channel technology (www.cichannel.org).

A key goal of this exploratory project, SciTube.tv, is to evaluate the acceptance both of authors uploading video clips and viewers watching those clips. The evaluation will consider both the length and type of format and, for each, whether the viewer has a rewarding viewing experience that increases their comprehension of the material being presented over conventional scientific journal articles. Additionally, SciTube.tv provides a rating system and the opportunity for virtual communities to gather around a particular "videopaper" through which a discourse can take place.

The results of this project will inform future implementation efforts which are expected to include extending the scope of authors beyond PLoS journals to develop a large video archive of scientific content, making this content available under a creative commons license framework to maximize reuse, and developing unique capabilities for searching. Additional ideas under consideration include enabling laboratories to have their own SciTube.tv channel where they can store protocols, educational video materials and so on, and provision of educational materials, simulations etc. for use by the general public.

The availability of an accessible and robust video resource can have very broad impact in enabling new means for disseminating scientific information and promoting collaboration, in developing new paradigms for education, and in communicating the excitement and promise of science to the general public.

DESCRIPTION (provided by applicant): SciVee Inc.'s major product is a Web 2.0 resource that can be found as http://www.scivee.tv and is a YouTube for scientists but much more, as will be outlined subsequently. SciVee represents a potentially exciting and significant enhancement in scholarly communication. SciVee aggregates multimedia content (video, podcasts, text and figures) on topics of scientific interest for an audience ranging from K12 to professional scientists. The product is free content (available under a Creative Commons 3.0 license) which can be broadly classified as either Pubcasts or scientific videos. Pubcasts integrate a 5-10 minute video presentation by the author(s) of a peer reviewed scientific paper with the open access content (if available otherwise just the abstract) of that paper to enhance one's ability to comprehend that content. Pubcasts of closed access papers consist of a video, supplementary slides, data etc. and the abstract of the published peer reviewed paper. Videos are presentations of a broad range of scientific topics not easily communicated by other media, notably print. Associated with Pubcasts and videos are communities of users that form around areas of common interest stimulated by the content. Communities exist for topics, laboratories, institutions, etc. Users comment and rate content as is typical of a Web 2.0 resource. The goals of SciVee are: " To stimulate continued interest in science by people of all ages with emphasis on retaining the interest of young minds who are turned off by the scientific stereotype and the textbook format as the only form of retaining that interest. " To engage the YouTube generation who are the next generation of leading scientists. " To facilitate the comprehension of an ever broadening body of scientific knowledge by professionals required to be ever more multi-disciplinary. " To create a new type of environment for scientific discourse. " To take advantage of the increasing body of full text open access (OA) scientific literature in ways that enhance learning and help promote the OA publishing model. SciVee was created in collaboration with the Public Library of Science (PLoS) and with a Small Grant for Exploratory Research (SGER) from the National Science Foundation (NSF). The grant paid to develop the Web site (content management system, backend database, redundant servers etc.) At present the site has 30,000 unique users per month, several thousand videos, 5000 community members and about 40 Pubcasts. The next stage of development and sustainability (Phase I) requires an evaluation of the proposed business model and the subsequent phase require enactment of the resulting modified business model (Phase II). PUBLIC HEALTH RELEVANCE: The dissemination of science in a new medium has the potential for global improvements in science research and education. This in turn will impact Public Heath.

The University of California San Diego is awarded a grant for planning activies leading to a conceptual design for an an S2I2 Institute for Translational Systems Biology (ITSB) that emphasizes biological 3-dimensional (3D) structures from molecule to cell and addresses the sustainability challenge. This virtual 3D cell provides the scientific framework to collect and disseminate software associated with all aspects of molecular and cellular biology in a way that can be understood by practicing scientists. We will draw from the App store model, which, while a software distribution paradigm in common use in daily life, has not been considered as a way to distribute, maintain and evolve scientific software. The app store model defines a source of software, a place to comment, rate and contribute to software; a place with an expectation of how that software will operate; and a place where software has standardized interfaces. The ITSB is a community driven project and the community will be bought together by a symposium and a series of focused workshops that: (I) explore where the science will be in 5 years from the world leading practitioners; (ii) smaller workshops that take that vision and define what software, data and tool development is needed to fulfill that vision in areas such as the biology of supramolecular assemblies, protein-protein interactions, pathway analysis and simulation; and (iii) a workshop that focuses on K12, undergraduate and professional education and dissemination through visual cues and organization of content that will train the next generation of translational biologists using the full power of the Internet. The 3D virtual cell web site will become a hub through which diverse practitioners can contribute, gain knowledge and interact.

Biology occurs at multiple scales, from molecules to cells to organisms to environments; scales which have traditionally been studied separately. Translational biology is now seeking to bring these disparate scales together to achieve a new level of understanding. This understanding requires new algorithm development and analysis tools that can operate on an increasingly large, diverse, complex and widely distributed body of digital biological data. Hence, translational biology is faced with cyberinfrastructure challenges related to data accessibility, software development, software reuse, and sustainability on a scale not seen before. The prior modus operandi of individual software development efforts needs to be complemented by a concerted community effort. Open source software repositories are useful in this regard but they do not focus on cyberinfrastructure to solve a biological grand challenge, but rather address a number of smaller challenges in a piecemeal fashion. As a result it could be argued that the current software development and maintenance cycle costs too much, takes too long, operates in too many silos, is unlikely to be unsustainable and cannot meet the ever increasing challenges of 21st century biological sciences. The broader impact of the ITSB is a virtual biological environment physically manifest as a center for advanced software and data infrastructure. In content it provides a source of data, software, tools and knowledge of the emergent 3D virtual cell. In concept it is a new model for aggregating developments in the field. As such anyone with an Internet connection can gain access to a collated and well-described set of data, tools and knowledge, materials that hitherto might only have been present in select laboratories and not easily accessible to a broad community of scholars from diverse backgrounds and institutions.