James A. Glazier - US grants
Affiliations: | Indiana University, Bloomington, Bloomington, IN, United States |
Area:
BiophysicsWe are testing a new system for linking grants to scientists.
The funding information displayed below comes from the NIH Research Portfolio Online Reporting Tools and the NSF Award Database.The grant data on this page is limited to grants awarded in the United States and is thus partial. It can nonetheless be used to understand how funding patterns influence mentorship networks and vice-versa, which has deep implications on how research is done.
You can help! If you notice any innacuracies, please sign in and mark grants as correct or incorrect matches.
High-probability grants
According to our matching algorithm, James A. Glazier is the likely recipient of the following grants.Years | Recipients | Code | Title / Keywords | Matching score |
---|---|---|---|---|
2000 — 2007 | Glazier, James | N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Biocomplexity--Multiscale Simulation of Avian Limb Development @ Indiana University 0083653 |
0.915 |
2004 | Glazier, James Alexander | R13Activity Code Description: To support recipient sponsored and directed international, national or regional meetings, conferences and workshops. |
Workshop: Complex Behavior in Unicellular Organisms @ Indiana University Bloomington DESCRIPTION (provided by applicant): This proposal requests partial funding for the workshop "Biocomplexity VI: Complex Behavior in Unicellular Organisms," jointly organized by the Biocomplexity Institute at Indiana University and the Biocomplexity Center at the University of Notre Dame. The workshop aims to be broader in scope and more interdisciplinary than other workshops, while remaining focused on a clearly defined problem. It will bring together researchers in many disciplines (including experimental and theoretical biology, biophysics, engineering, mathematics and computer science) to discuss current and future problems in collective phenomena in single-celled organisms, including comparison between prokaryotic and eukaryotic behaviors, motility and taxis, multicellular aggregation and biofilms, distributed behavior and intercellular signaling, differentiation and development and pathenogenic and symbiotic interactions. The talks will cover length scales from single molecule interactions and genetics to systems biology and ecology. A specific goal of the workshop is to bring experimentalists and modelers and engineers and basic researchers together and to include people who would not normally attend the same conference. This cross fertilization should improve our understanding of the fundamental biology of collective behaviors, lead to more useful models and engineering techniques, initiate new modeling efforts, promote collaborations between experimentalists and modelers, transfer best practice between subdisciplines and encourage more holistic approaches to problem solving. We have already more than forty confirmed speakers from the USA, Canada, Europe, Israel and Japan and anticipate a total participation of about 100 including a substantial number of postdoctoral fellows and graduate students. The workshop will include a significant educational component directed at graduate students and junior scientists, especially those not currently involved in complex phenomena in single celled organisms, but interested in learning about open problems, methodologies and opportunities. As part of our outreach effort we will sponsor a large public lecture for nonscientists and interested members of the community at large to be given by Dr. Eshel Ben-Jacob of the Weizmann Institute, Israel. |
1 |
2004 — 2005 | Brun, Yves (co-PI) [⬀] Fuqua, William (co-PI) [⬀] Madey, Gregory (co-PI) [⬀] Glazier, James Maurice, Patricia |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ Indiana University This project will support the International Workshop Biocomplexity VI: Complex |
0.915 |
2005 — 2006 | Glazier, James Schnell, Santiago |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ Indiana University Even when full genomic sequences for an organism are available, the functions and interactions of only a small number of gene components are clear. Presently, the functions of uncharacterized proteins have usually been inferred on the basis of sequence similarities, common structural motifs, gene order, gene fusion events, or similarities in gene expression. Recently, new mathematical and computational methods have been introduced for functional predictions based on the role of genes in networks. These methods allow us to perform functional predictions for proteins independent of homologies in structure or sequence and provide a way to characterize proteins that have not yet been studied using published biological data from high-throughput technologies. This proposal requests partial funding for the workshop "Biocomplexity VII: Unraveling the Function and Kinetics of Biochemical Networks: From Experiments to Systems Biology," organized by the Biocomplexity Institute and the School of Informatics at Indiana University. The Biocomplexity VII workshop aims to bring together specialists in a broad array of methodologies to see how they can combine to explicate the functions of genes and proteins in a network context by developing mathematical and computational approaches suited for the analysis of high-throughput data sets. The objectives of the workshop are to: (i) To explore and present the development of new experimental and theoretical approaches for the purposes of reconstructing complex biochemical networks; (ii) To promote interaction between engineers, physicists, mathematicians, biologists, and chemists with interests in all aspects of reconstructing complex biochemical networks, and (iii) To provide a forum for junior faculty and graduate students to interact with a wide range of experts. |
0.915 |
2005 — 2007 | Glazier, James Alexander | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Msm - Multiscale Studies of Segmentation in Vertebrate * @ Indiana University Bloomington [unreadable] DESCRIPTION (provided by applicant): [unreadable] In vertebrates, segmentation during early embryogenesis forms somites, recurring tissue modules, distributed along the anterior-posterior axis. Segmental structures give rise to the ribs, vertebrae, limbs, associated muscles, and central and peripheral nervous system. Failures in segmentation can be lethal or cause serious developmental abnormalities. Somitogenesis relies on a molecular clock, growth factor gradients and the expression of cell-adhesion and extracellular matrix (ECM) molecules. Segmentation requires complex, large-scale (millimeter) coordinated movement of cells and ECM. Despite increasing knowledge of the molecular mechanisms underlying segmentation, the interplay [unreadable] of molecular-, cell- and tissue-level mechanisms during somitogenesis remains obscure. Because of the tight feedback between subcellular and large-scale processes, no single-scale model can simulate somitogenesis. Current models address only the subcellular or macroscopic levels and do so separately. A successful multiscale model will answer one of developmental biology's great open problems: how do the molecular mechanisms of fate determination couple to large-scale tissue deformations? The proposed work will test the hypothesis that during segmentation, physical forces and biomaterial properties must coordinate with a moving biological oscillator, the segmentation clock, for successful somitogenesis. We will both model and conduct experiments on key developmental mechanisms ranging from local regulation of cell adhesion proteins (micrometers) to global tissue deformations (millimeters). We will develop novel theories and modeling approaches to bridge these scales. Our methodology has four major components: 1) Identifying (discovering) mechanisms and relevant models at each scale. 2) Determining the parameters for each level of model. 3) Validating [unreadable] model results. 4) Testing model predictions of normal and abnormal behaviors, e.g. inhibition or overproduction of adhesion molecules. The techniques and insights the research will produce will apply to other developmental processes. The software we develop will form the core of an open-source, multiscale and general purpose Tissue Simulation Toolkit, which other researchers can apply to this and other developmental problems. The proposed research contributes to public health by addressing the causes of a significant subset of the developmental malformations which occur in approximately 150,000 infants born each year in the USA (1 out of 28 births). Disturbing somite formation results in Klippel-Feil syndrome.spondylocostal dysostosis.Jarcho-Levin syndrome, congenital scoliosis and kyphosis, Goldenhar syndrome, and spina bifida, among others disorders. Studying the developmental [unreadable] mechanisms in vertebral patterning will aid in the identification of protective or potentially disruptive factors for normal somitogenesis and could potentially impact treatments for the prevention of vertebral patterning disorders. [unreadable] [unreadable] |
1 |
2007 — 2009 | Glazier, James Alexander | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development and Improvement of Tissue Simulation Toolkit @ Indiana University Bloomington [unreadable] DESCRIPTION (provided by applicant): Project Summary: We propose to develop an open-source modeling environment, the Tissue-Simulation Environment (TSE), for the cell-based modeling of the structure and behavior of tissues and organs using the Cellular Potts Model (CPM) formalism. While groups worldwide have used the CPM methods to model biomedical phenomena, including vascular development, tumor growth, wound healing and the immune system, no open-source package currently supports this class of model. Our Specific Aim is that the TSE should provide modeling capability comparable to or better than other CPM simulations and be usable by and attractive to a broad community of biomodelers and experimentalists. To accomplish this aim we will provide a highly expandable core simulation engine, numerous validated sample biological models, a flexible and intuitive graphical user interface with visualization capability, extensive documentation and a number of modules describing biological processes not included in other CPM simulations. In addition we will provide user-training workshops and conduct ongoing user-need surveys. In response to the NIH Roadmap's call for interoperability and multiscale simulations, the TSE will also provide connectivity to other major subcellular and tissue-level software packages through a program of markup- language development and support. The TSE will also provide a mechanism to collect, validate and release user-submitted modules, models, bug reports and fixes to ensure that it develops rapidly and reliably in a way responsive to its users. Relevance: Simulations of cell interactions during embryonic development, wound healing, and disease can play an important role in experimental biomedical studies, help with the interpretation of experimental results, suggest experiments, predict experimental outcomes and lead to deeper understanding of fundamental biological mechanisms, thus expediting the understanding of diseases and the development of treatment strategies. [unreadable] [unreadable] [unreadable] |
1 |
2008 — 2011 | Glazier, James Alexander | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ibcst - Competitive Renewal of Msm: Multiscale Studies of Segmentation in Verterb @ Indiana University Bloomington DESCRIPTION (provided by applicant): This competitive renewal extends the successful work (35 published papers) funded under 5R01GM076692-01 Multiscale Studies of Segmentation in Vertebrate Embryos to develop multiscale simulation tools for the simulation of somite formation in chicken. The strategic context of the current proposal is to unify the multiple accomplishments achieved during the original funding period into a coherent model of somitogenesis and to deliver the primary recommendation of the NIH-led Interagency Modeling and Analysis Group (IMAG) Miniworkshop and Principal Investigator's Meeting on Model Sharing, April 11-12, 2007: "a focused demonstration project for multiscale simulation techniques, which addresses a well- defined, specific problem in developmental biology, which includes a variety of biological mechanisms of importance throughout development and for which a unified multiscale approach is essential." Chick somitogenesis is an excellent choice of demonstration project because it is well- characterized experimentally, requires simulation of most fundamental developmental mechanisms, and requires both the unification of existing methodologies at multiple scales (in this case merging the widely-employed, open-source software packages Systems Biology Workbench (SBW) for subcellular modeling and CompuCell3D (CC3D) for multicell modeling into a Tissue-Simulation Environment (TSE)) and the development of a number of key additional software components of broad utility in developmental-biology simulation and in critical biomedical areas such as cancer and vascular research. This proposal leverages the investment NIGMS has recently made in software infrastructure development under 1R01GM077138-01A1 to Glazier and 1R01GM081070-01A1 to Sauro, which, while they greatly increase the scope of CC3D and SBW separately (by supporting improved user interfaces for model generation, execution and analysis;enhanced scripting- language support, development of testing and validation modules, improving documentation, training materials and user support), do not cover the development or parallelization of a merged SBW/CC3D, or the deployment of a biologically-meaningful demonstration project. PUBLIC HEALTH RELEVANCE: Simulations of cell interactions and underlying molecular mechanisms during embryonic development can play a vital role in experimental biomedical research, help with the interpretation of experimental results, suggest experiments, predict experimental outcomes and lead to a deeper understanding of fundamental biological mechanisms, thus expediting the understanding of diseases and the development of treatment strategies. Successful completion of the presented research plan will improve the involvement of medical institutions and industry, and their interaction in the development of modeling tools and their effective use in the creation of novel drugs and treatments. |
1 |
2011 — 2015 | D'souza, Roshan M (co-PI) [⬀] Glazier, James Alexander |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Competitive Renewal of Development, Improvement and Extension of the Tissue Simu @ Indiana University Bloomington DESCRIPTION (provided by applicant): During two-and-a-half years of funding under NIH GM077138, the EPA's ComTox program, the Dundee computational oncology effort and an increasing number of developmental biologists and tissue engineers have adopted CompuCell3D (CC3D) as a modeling platform. CC3D has become the most widely accepted standard for multi-scale, multi-cell (MSMC) simulations of developmental phenomena and related diseases, with more than 100 trained users, because its open-source combination of the multi-cell capabilities of the Glazier-Graner-Hogeweg (GGH) model, the SBML-compatible subcellular biochemical networks, and continuum and finite-element modeling of tissue-level phenomena, sophisticated user interfaces and scripting capabilities allow rapid construction of useful biomedical models with tunable levels of modeling detail. Motivated by the requests of our increasing number of translational users, this competing renewal will develop a parallel (Graphical Processing Unit (GPU), multi-core and cluster) CC3D2 with fluid-flow support providing up to a hundred-fold increase in speed over CC3D plus the ability to run very large-scale simulations (many cm3, 107-109 cell, whole embryo/organ) with a simple migration path from laptop to diverse parallel architectures (Specific Aim 1). It is significant, because CC3D2 will transform the power of MSMC modeling to allow the development of the detailed, verifiable models required for future clinical-research applications, achieving the goal identified by the NIH-led Interagency Modeling and Analysis Group (IMAG) group: "the development of open source, multi-scale biological simulation environments which run both on single processors and parallel computers and which ..., [permit] users to select the level of simulation detail without further modifying their simulations." It is innovative because it combines the existing expertise of the CC3D development team and the extensive GPU and parallelization experience of the D'Souza group to provide a robust parallel MSMC environment and the first GPU-based implementation of the GGH methodology to allow simulations which were formerly unachievable. As requested by our clinical and biomedical users, CC3D2 will provide an innovative, fast and biologically- intuitive approach to model design, with a novel Cell Behavior Model Specification Language (CBMSL) (Specific Aim 3) and the first sharable graphical model definition available for MSMC (Specific Aim 2). CBMSL will allow researchers to focus on biology rather than computational details and greatly facilitate model cross-validation and sharing, providing an important use-case for future MSMC model-description standardization efforts. Graphical workflow control and enhanced user support and documentation (Specific Aim 4) will further improve CC3D2 usability and increase user adoption. PUBLIC HEALTH RELEVANCE: Biological simulation tools used in studies of development are increasingly being used to study medically important problems such as tumor growth and metastasis, toxicology and progression of diseases. However, the closed-source, hard-coded nature of most current simulation tools, and their limited simulation size, impede this transition. As an open-source, sharable simulation environment, CC3D2 is an important step towards the use of mechanism-based simulations in clinical research because it will provide a 100X increase in speed over current tools, allow simulation of organ-sized regions, and facilitate validation and reuse of simulations. |
1 |
2012 — 2016 | Glazier, James | N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Idbr: Collaborative Research: Real Time Secretion: Single Cell Analyzer @ Indiana University IDBR: Collaborative Research: Real time secretion: single cell analyzer |
0.915 |
2012 — 2014 | Glazier, James Sauro, Herbert |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
@ Indiana University This Pan-American Advanced Studies Institutes (PASI) award, jointly supported by the NSF and the Department of Energy (DOE), will take place in July, 2013 at the Universidade Federal do Rio Grande do Sul (UFRGS) in Porto Alegre, Rio Grande do Sul, Brazil. Organized by Dr. James A. Glazier of the Physics Department at Indiana University in Bloomington, the institute will focus on many of the key mathematical approaches currently used in modeling biological phenomena in contemporary biology. The development and function of tissues and organs rely on a complex web of interactions that occur on a multitude of scales ranging from individual proteins to tissue networks. The PASI will gather leading researchers from a variety of modeling disciplines to teach their methodologies through lectures and computer laboratories, and to promote interdisciplinary collaborations among participants in order to address key biological problems. PASI participants will include experimental biologists, computational biologists, and mathematical biologists at the advanced undergraduate, graduate and post-graduate levels. |
0.915 |
2012 — 2015 | Glazier, James Alexander Stern, Claudio D (co-PI) [⬀] Stern, Claudio D (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Competetive Renewal of Msm: Multiscale Studies of Segmentation in Vertebrates @ Indiana University Bloomington DESCRIPTION (provided by applicant): The vertebral column and skeletal musculature derive from embryonic structures called somites, which form sequentially from head to tail. Normal musculoskeletal development requires the correct number of cells in each somite and that each somite acquires its correct axial address. Perturbations can lead to malformations of the spine ranging from complete disarray of the vertebral elements (e.g. spondylocostal and spondylothoracic dysostoses and dysplasias) to deviations of the spine (lordosis, kyphosis, and scoliosis) and misspecification of the regional identity of skeletal elements (e.g. Klippel-Feil syndrome). Research in the last two decades has uncovered molecular oscillators and gradients of growth factors hypothesized to control somite size and identity. However, little is known about how (or if) these molecular players relate to cell behaviors like cell adhesion, proliferation and migration that result in somite patterning. In part this uncertainty is due to the spatiotemporal complexity of somitogenesis, the number of mechanisms involved and the relative lack of cross-talk between model and experiment in the past. This project undertakes a multiscale approach to address all three issues. The NIH-led Interagency Modeling and Analysis Group (IMAG) has identified as key goals the development of open-source, multi-scale biological simulation environments and the deployment of demonstration projects that integrate models operating at different scales. This project will build comprehensive 3D multiscale predictive models of vertebrate somitogenesis able to generate and test specific hypotheses concerning the mechanisms of interspecies differences (as a model of individual to individual variability and robustness) and perturbations. It will refine a tissue simulation environment (CC3D) to improve its usability to the community, perform new biological experiments to collect data as inputs for 3D somitogenesis models and to test model predictions, and deploy models and experimental data using emerging standards for sharing of multicellular information (CBO, CBMSL). Specifically, it will: 1) develop new 3D models to integrate behaviors at molecular, cellular and tissue scales to reproduce the normal dynamics of segmentation and test them by quantitative measurements using advanced time-lapse fluorescence microscopy and microfluidics-based gradient-cell technology; 2) use a novel experimental paradigm that allows segmentation to be studied independently of the molecular segmentation clock, for challenging and validating the segmentation models; 3) extend the models and experiments to understand how somites acquire positional identities and 4) open-source release data and models in sharable formats. In addition to generating a predictive model for vertebral column development and its anomalies, this project should enable future studies of the development of other organs and establish the role of multi-scale modeling in biomedical science. Its emphasis on model and data share ability will promote efficient sharing of resources, tools and models among biomodelers and experimentalists, significantly reducing duplication of effort. PUBLIC HEALTH RELEVANCE: Errors in somite segmentation during embryogenesis can lead to malformations and deviations of the spine (e.g., scoliosis, lordosis, kyphosis, spondylocostal and spondylothoracic dysostoses and dysplasias and Klippel-Feil syndrome). Surprisingly little is known about the mechanisms that control somite size, shape, axial identity and pattern in normal development, and consequently about the etiology of congenital disorders of the spine. This project closely couples modeling at multiple scales (molecules, cells, and tissue and body pattern) with novel experimental approaches to validation to produce models that will elucidate disease etiology and identify candidates for genetic screening and diagnostic methods. |
1 |
2014 — 2017 | Dunn, Kenneth W (co-PI) [⬀] Glazier, James Alexander Klaunig, James E (co-PI) [⬀] |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Development of a Multiscale Mechanistic Simulation of Acetaminophen Induced Liver @ Indiana University Bloomington DESCRIPTION (provided by applicant): Pharmacological and toxicological processes occur across a wide range of spatial and temporal scales and include multiple organ systems. A Systems Biology in silico toxicological model must include submodels that cover the multiple scales and the multiple tissues relevant to human medicine and toxicology. We will develop a liver centered mechanism based multiscale in silico simulation framework for xenobiotic toxicity and metabolism that incorporates four key biological scales: Population genetic and exposure variation scale Physiologically Based Pharmacokinetic (PBPK) whole body scale Tissue level and multicellular scale Subcellular signaling and metabolic pathways scales The multiscale in silico simulation will be centered on the liver, a critical organ in many toxicological, pharmacological, normal and disease processes. For our initial simulations of toxic challenge to the liver we will build a mechanism based in silico simulation of Acetaminophen (APAP) toxicity. APAP is a widely used over-the-counter pain reliever and fever reducer. An acute overdose of APAP is a leading cause of liver failure in the western world. APAP overdose leads to centrilobular liver necrosis that can progress to liver failure and in some cases patient death. Our multiscale in silico simulation will link existing open source modeling tools for the various spatiotemporal scales into an aggregate in silico model. This approach allows us to leverage existing tools, modeling modalities and models at the individual biological scales. Furthermore, this approach facilitates swapping models at individual scales without extensive modification of the sub-models at the other scales and allows us to leverage existing model development tools and resources. The complete multiscale in silico model will provide a mechanism based framework that incorporates effects at the various scales and will also provide a framework to predict changes in clinically used serum markers of liver function and failure. Our in silico simulation will be calibrated using microscopic imaging in the liver of a living mouse, mouse liver immune-histology, along with standard histology and serology in animal studies of APAP toxicity. The proposed in silico model is a first step in toxicity prediction 1. 2. 3. 4. simulatio that ultimately will lead to improved techniques for prediction toxicity of therapeutic agents and environmental toxins while simultaneously reducing the need for animal toxicity studies. |
1 |
2017 — 2022 | Macklin, Paul Glazier, James Douglas, Trevor (co-PI) [⬀] Jadhao, Vikram (co-PI) [⬀] Fox, Geoffrey [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Network For Computational Nanotechnology - Engineered Nanobio Node @ Indiana University In its original formulation due to Feynman almost six decades back, nanotechnology began around a simple but powerful vision of a device engineered to write the entire Encyclopedia Britannica on the head of a pin. Nanotechnology now is a multidisciplinary field where devices are designed for applications in a diverse array of fields such as electronics, medicine, and energy using principles from engineering, physics, materials science, chemistry, computing, and biology. The safe and successful application of nanotechnology in the biological realm demands an advance in the original vision of Feynman due to the inherent multiscale nature of biology. Engineering of these nanoBIO devices must be based on the knowledge of how nanotechnology-based devices interact with biological systems at the protein, cell, tissue, and organ levels. The Engineered nanoBIO node at Indiana University (IU) will develop a powerful set of integrated computational nanotechnology tools that address this complex, multiscale problem and facilitate the discovery of customized, efficient, and safe nanoscale devices for biological applications. These computational tools will be tested and validated experimentally, and they will be integrated with IU's key cyberinfrastructure strengths in high-performance computing and scalable data-analysis platforms. They will meet critical national health needs as they find applications in nanomedicine by significantly enhancing the targeting and imaging capabilities of engineered nanoparticles, thus increasing our ability to generate new life-saving medicines for cancer treatment. |
0.915 |
2017 — 2020 | Glazier, James Alexander | R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
@ Indiana University Bloomington Summary: We propose to transform our CompuCell3D virtual tissue simulator into a bona-fide computer aided engineering (CAE) system for bio-medical research focused on the biologically-intuitive description and design of multi- cell models of tissues and organs (Virtual Tissues). This will include descriptions of biological mechanisms, components, processes and outcomes. Mechanism-based models of this type will allow researchers to explore the systemic outcomes of molecular and cellular perturbations (characterized using in vitro and high-throughput experiments) to extract mechanistic understanding of normal and disease states. CAE programs allow engineers to construct virtual representations (computational models) of components, assemble them into complex devices, and simulate their behaviors and interactions in virtual experiments. CAE programs allow engineers to evaluate the performance, reliability and failure modes of proposed devices without actually having to physically build those devices. CAE platforms enable the capture of domain knowledge in validated, sharable and reusable components and composite models and to leverage big-data to abstract knowledge, increasing the speed, efficiency and reliability of experiment and design. Significance: A key impediment to adoption of CAE simulation approaches in biology and medicine is not the speed or efficiency of simulation software, but rather the lack of appropriate human-computer interaction between life-science researchers and simulation software. Increasing the uptake of CAE tools in biomedicine requires the development of biologically motivated languages and interfaces that facilitate the creation of mechanism-based models of biological systems, and embed biological knowledge within these models in a way that promotes knowledge validation, mining, recovery and reuse. Innovation: We will create a platform for building modular, sharable and reusable virtual-tissue models (including patient-specific models that integrate patient-derived measurements) that capture and integrate biological and mechanistic knowledge and experimental observations. Building virtual-tissue models requires combining and integrating a range of components from different scales. We develop a new hybrid programming language based on biological rather than computational concepts that naturally expresses the complex multi-scale objects and dynamic interactions in a unified way. To our knowledge, this language is the first if its kind to allow biological components and models to be visually created and composite and enables the capture, search, formalization, extraction and reuse of domain knowledge. Our platform will transform these models into executable simulations, creating virtual experiments which allow direct comparison with laboratory experiments. We will also develop tools to optimize virtual-tissue models against qualitative and semi-quantitative experimental data, providing robust techniques to explore diverse hypotheses and parameter ranges, and optimally employ available experimental data. These approaches will reduce the effort required to develop understanding of normal and pathological conditions and provide a route to extraction of knowledge from heterogeneous biological big data. |
1 |
2020 | Glazier, James Alexander Sauro, Herbert M. [⬀] Sluka, James P Somogyi, Endre |
U24Activity Code Description: To support research projects contributing to improvement of the capability of resources to serve biomedical research. |
Dissemination of Libroadrunner and Compucell3d @ University of Washington Project Summary/Abstract This proposal will make Virtual Tissue modeling, which spans scales from subcellular biological networks through cells to tissues and whole organisms and populations, more accessible and useful to biomedical researchers by improving and integrating two open-source computational modeling environments, subcellular Tellurium, and multicellular CompuCell3D (CC3D). Both tools aim to simplify model design by separating biologically-motivated model specification from the computer code which runs the simulation. Impediments to adoption of Virtual Tissue modeling include: 1) lack of familiarity, 2) substantial effort required to learn to design, build, execute and apply models and 3) concern over sustainability if software tools disappear or if users need to migrate between platforms. To address these concerns, we will: 1) Apply a design architecture based on documented and tested reusable software components to harden and integrate Tellurium and CompuCell3D, improving long term sustainability by simplifying open- source development. 2) Streamline the learning process for model specification, execution, and analysis to reduce barriers to adoption; 3) Simplify and harmonize installation and use across desktop, HPC and web (cloud/cluster) installations, and 4) Disseminate upgraded tools and expand the user and developer base via workshops, support infrastructure and online tutorials. |
0.951 |