Modeling and Bioinformatics Core

建模和生物信息学核心

基本信息

批准号：
8919395
负责人：
Jeremy S Edwards
金额：
$ 44.34万
依托单位：
UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8919395
关键词：
Adaptor Signaling Protein Adhesions Affinity Allergens Allergic inflammation Archives Area Asthma Basophils Biochemical Bioinformatics Biological Assay Biological Models Biology Cancer Control Cell membrane Cells Clathrin Code Colon Carcinoma Communicable Diseases Communities Complex Computer Simulation Coupled Data Data Analyses Data Set Dendritic Cells Development Diffusion Discipline Dissociation Drug Combinations Education and Outreach Endosomes Engineering Enzymes Epidermal Growth Factor Receptor Evaluation Event Experimental Models Exposure to Family Fc Receptor Flow Cytometry Fluorescence GTP Binding Generations Goals Growth Factor Receptors Health Human Hydrolysis Hypersensitivity ITAM IgE Receptors Image Image Analysis Immune Immune System Diseases Immunologic Receptors Immunology Inflammation Mediators Kinetics Lead Life Ligands Link Malignant Neoplasms Malignant neoplasm of ovary Measures Mediating Mediator of activation protein Membrane Membrane Protein Traffic Methods Microfluidic Microchips Microscopy Minority Modeling Modification Mutagenesis National Institute of General Medical Sciences Natural Immunity Neoplasm Metastasis New Mexico Online Systems Outcome Output Ovary Pathway interactions Pattern Physicians Post-Translational Protein Processing Process Protein Dynamics Protein Isoforms Proteins Protocols documentation Quantum Dots Reaction Receptor Protein-Tyrosine Kinases Receptor Signaling Recombinants Regulation Research Research Infrastructure Research Personnel Research Project Grants Research Training Resolution Role Science Scientist Signal Pathway Signal Transduction Signaling Protein Site Small Interfering RNA Specialist Students Surface Symptoms System Systems Biology Technology Time Training Programs Translations Ursidae Family Woman Xenograft Model adaptive immunity base carcinogenesis career computerized tools dectin 1 differential expression fungus high throughput screening human disease imaging modality improved in vivo innovation insight instrumentation intravital imaging mathematical model meetings member migration models and simulation mutant new technology novel particle pathogen predictive modeling programs protein transport receptor receptor internalization response single molecule spatiotemporal symposium targeted treatment tool trafficking tumor web site

项目摘要

SUMMARY This application seeks competitive renewal of the NIGMS-supported New Mexico Center for the Spatiotemporal Modeling of Cell Signaling (Spatiotemporal Modeling Center; STMC). Our Center focuses remarkable strengths in biology, technology, modeling and simulation on understanding how the spatial proximity, dynamics, interactions and trafficking of membrane receptors and signaling proteins together determine the outcome of signal transduction networks. Research foci include the ITAM family of immunoreceptors, particularly the high affinity IgE receptor (FcεRI) that is responsible for triggering both the symptoms and progression of allergic inflammation. The innate immune receptor, Dectin-1, bears a truncated “hemITAM” and its novel signaling control will be studied in detail over the renewal period. STMC researchers also specialize in the EGFR and other receptor tyrosine kinases. A major focus in this proposal is the unusual cross-talk between EGFR/erbB receptors and the Met/Ron family – and their complex control of carcinogenesis and metastasis. The experimental teams will quantify the distributions, mobility, interactions and post-translational modifications of receptors and adaptors that mediate both signaling and trafficking after exposure to ligand. Each research project is highly integrated with respect to experimental and mathematical modeling components. Computational specialists in the STMC’s Modeling and Bioinformatics Core include pioneers in the field of rule-based modeling approaches, which are applied to develop mechanistic kinetic models and to implement powerful spatial stochastic platforms that consider the contribution of the membrane landscape to receptor signaling. In vivo and in silico tumor models will provide insights into the mechanisms by which the erbB and Met receptors control responses to targeted therapies. Multiple new technologies will be deployed within the projects, including real-time confocal and hyper-spectral microscopy with quantum dot- tagged ligands to track receptor distributions and interactions in live cells, novel TIRF imaging assays on live cells, photo-bleaching protocols that quantify protein-protein reaction kinetics, and novel microfluidic devices to image events in rare primary cells and quantify the release of mediators. The STMC community is supported by strong cores. The STMC Super-resolution and Image Analysis Core provides new instrumentation and probes to access protein-protein dynamics at the 10 nm scale and is dedicated to the improved analysis and cross-platform integration of image data, as well as the archiving and sharing of both image and biochemical data, and the broad dissemination of data, code and models. The STMC Training and Outreach Core provides exceptional opportunities for young biomedical, mathematical, statistical, physical and computational scientists, as well as engineers and physicians, to build exciting and productive careers with potential to impact human health. The STMC Administration Core maximizes the ability of center members to conduct innovative science and will continue to support our aspiration to serve as a national model for diversity in Systems Biology through the continued recruitment and advancement of women and minorities.

概括该申请寻求竞争性更新，以诺格姆斯支持的新墨西哥中心细胞信号传导的时空建模（时空建模中心； STMC）。我们的中心专注于生物学，技术，建模和模拟方面的显着优势，了解空间如何膜受体和信号蛋白的接近，动力学，相互作用和运输在一起确定信号传输网络的结果。研究焦点包括ITAM家族免疫感受器，特别是高亲和力IgE受体（FCεRI），负责触发这两种受体过敏性炎症的症状和进展。先天免疫受体Dectin-1带有截短的 “ Hemitam”及其新型信号控制将在续签期间进行详细研究。 STMC研究人员还专门研究EGFR和其他受体酪氨酸激酶。该提案的主要重点是不寻常 EGFR/ERBB受体与Met/Ron家族之间的串扰 - 他们对癌变和转移。实验团队将量化分布，移动性，互动以及对接收器和适配器的翻译后修饰暴露于配体。每个研究项目都在实验和数学方面高度融合建模组件。 STMC建模和生物信息学核心的计算专家包括基于规则的建模方法领域的开拓者，用于开发机械动力学模型并实施强大的空间随机平台，以考虑膜的贡献景观到受体信号。体内和硅肿瘤模型将通过 ERBB和符合受体控制对靶向疗法的反应。多种新技术将是部署在项目中，包括带有量子点的实时共聚焦和超光谱显微镜标记的配体以跟踪活细胞中接收器分布和相互作用，现场新型TIRF成像测定细胞，量化蛋白质 - 蛋白质反应动力学的光泽方案，以及新型的微流体设备稀有原代细胞中的图像事件并量化了介体的释放。 STMC社区得到了强大的核心的支持。 STMC超分辨率和图像分析核心提供新的仪器和问题以在10 nm等级访问蛋白质 - 蛋白质动力学，并且致力于改进图像数据的分析和跨平台集成以及归档和共享图像和生化数据，以及数据，代码和模型的广泛传播。 STMC培训和外展核心为年轻的生物医学，数学，统计，物理和计算科学家以及工程师和医师，以建立令人兴奋的和有可能影响人类健康的生产事业。 STMC管理核心最大化中心成员进行创新科学的能力，并将继续支持我们的愿望通过持续招募和进步的系统生物学多样性的国家多样性模型妇女和少数民族。