Super-Resolution and Data Analysis

超分辨率和数据分析

• 批准号: 8919394
• 负责人: Keith A Lidke
• 金额: $ 29.2万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 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/8919394
• 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

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 NIGMS 支持的新墨西哥中心的竞争性更新 细胞信号传导的时空建模（时空建模中心；STMC）。我们中心专注于 在理解空间如何变化方面，在生物学、技术、建模和模拟方面具有显着的优势 膜受体和信号蛋白的邻近性、动态性、相互作用和运输 确定信号转导网络的结果。研究重点包括 ITAM 系列 免疫受体，特别是高亲和力 IgE 受体 (FcεRI)，负责触发 过敏性炎症的症状和进展。先天免疫受体 Dectin-1 具有截短的 “hemITAM”及其新颖的信号控制将在更新期间进行详细研究。 STMC研究人员 还专注于 EGFR 和其他受体酪氨酸激酶。该提案的一个主要焦点是不寻常的 EGFR/erbB 受体与 Met/Ron 家族之间的串扰 - 及其复杂的控制 致癌和转移。实验团队将量化分布、流动性、相互作用 以及介导信号传导和运输的受体和接头的翻译后修饰 暴露于配体。每个研究项目在实验和数学方面都高度集成 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先驱，该方法用于开发机械动力学 模型并实现考虑膜贡献的强大空间随机平台 景观到受体信号传导。体内和计算机肿瘤模型将通过以下方式提供对机制的见解： erbB 和 Met 受体控制对靶向治疗的反应。多项新技术将 在项目中部署，包括带有量子点的实时共焦和高光谱显微镜 标记配体追踪活细胞中的受体分布和相互作用，新型 TIRF 活细胞成像分析 细胞、量化蛋白质-蛋白质反应动力学的光漂白方案以及新型微流体装置 罕见原代细胞中的图像事件并量化介质的释放。 STMC社区有强大的核心支持。 STMC 超分辨率和图像分析核心 提供新的仪器和探针以获取 10 nm 尺度的蛋白质-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 图像和生化数据的共享，以及数据、代码和模型的广泛传播。这 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生，共同构建令人兴奋和 具有潜在影响人类健康的生产性职业。 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 通过持续招募和提升系统生物学多样性的国家模型 妇女和少数民族。