Center for Spatiotemporal Modeling of Cell Signaling

细胞信号传导时空建模中心

基本信息

批准号：
8919387
负责人：
Bridget S Wilson
金额：
$ 221.68万
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 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8919387
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 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 public health relevance receptor receptor internalization response single molecule spatiotemporal symposium targeted treatment tool trafficking tumor web site

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 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 public health relevance receptor receptor internalization response single molecule spatiotemporal symposium targeted treatment tool trafficking tumor web site

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项目摘要

DESCRIPTION (provided by applicant): 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 (Fc¿RI) 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.

描述（由应用程序提供）：本应用程序寻求诺格姆斯支持的新墨西哥中心的竞争性更新，用于细胞信号的时空建模（时空建模中心； STMC）。我们的中心将生物学，技术，建模和模拟的显着优势集中在理解膜受体和信号蛋白的空间接近，动力学，相互作用和运输中如何共同确定信号转导网络的结果。研究焦点包括ITAM的免疫受体家族，特别是负责触发过敏性炎症的症状和进展的高亲和力IgE受体（FCCORI）。先天免疫受体Dectin-1带有截断的“ Hemitam”，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EGFR/ERBB受体与MET/RON家族之间的异常串扰及其对癌变和转移的复杂控制。实验团队将量化受体和适配器的分布，移动性，相互作用和翻译后修饰，这些受体和适配器在暴露于配体后介导信号传导和运输。每个研究项目都在STMC建模中的实验和数学建模计算专家方面高度整合，并且生物信息学核心包括在基于规则的建模方法领域中的先驱，这些核心将用于开发机械动力学模型和实施强大的空间随机平台，以实现考虑膜景观对受体构成的贡献。体内和硅肿瘤模型将提供有关ERBB和MET受体控制靶向疗法反应的机制的见解。项目将部署多种新技术，包括带有量子点标记的配体的实时共聚焦和超光谱显微镜，以跟踪活细胞中的接收器分布和相互作用，新颖的TIRF成像在活细胞上，照片揭示的协议，这些协议，这些协议，这些协议量化蛋白质 - 蛋白质反应动力学和新型的微流体装置来对稀有原代细胞中的事件进行图像，并量化介体的释放。 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了新的仪器和问题，可在10 nm尺度上访问蛋白质 - 蛋白质动力学，并致力于改进的分析和跨平台图像数据的集成以及图像和生物化学数据的归档和共享，以及数据，代码和模型的广泛散布。 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提供了极大的机会，以建立具有影响人类健康的激动人心和产品职业。 STMC管理核心核心通过持续招募和妇女和少数群体的晋升来支持我们的中心成员进行创新科学的能力，并将继续支持我们成为系统生物学多样性的国家模型。