Research Project 2: Elucidating the mechanisms and consequences of erbB/Met famil

研究项目2：阐明erbB/Met家族的机制和后果

• 批准号: 8767024
• 负责人: Diane Lidke
• 金额: $ 35.79万
• 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/8767024
• 关键词: Animals; Behavior; Biochemical; Biological Assay; Biology; Cell Fate Control; Cell Shape; Cell physiology; Cells; Colonic Neoplasms; Combined Modality Therapy; Computer Simulation; Detection; Drug resistance; Environment; Event; Family; Fostering; Goals; Human; Image; Lead; Life; Ligands; Malignant Neoplasms; Membrane; Microscopy; Mission; Modeling; Molecular; Neoplasm Metastasis; Outcome; Pharmaceutical Preparations; Physiological; Process; Proteins; Public Health; Receptor Protein-Tyrosine Kinases; Regulation; Research; Research Project Grants; Role; Shapes; Signal Pathway; Signal Transduction; Systems Biology; Testing; Work; biophysical techniques; drug sensitivity; extracellular; in vivo; in vivo imaging; innovation; mathematical model; meetings; member; neoplastic cell; novel; ovarian neoplasm; protein protein interaction; receptor; research study; response; single molecule; spatiotemporal; tumor growth; tumorigenesis

Project 2: Elucidating the mechanisms and consequences of erbB/Met family crosstalk Summary Diane Lidke, Project PI This project focuses on crosstalk between Receptor Tyrosine Kinases (RTKs) that trigger intracellular signaling cascades and control important cellular processes. We will apply state-of-the art microscopy (single molecule, single cell and in vivo) with biochemical assays and mathematical modeling - across five spatial scales - to provide a comprehensive picture of how receptor crosstalk modulates cell response. Our target receptors are members of the erbB and Met RTK families, shown to be important in oncogenesis, metastasis and drug resistance. Our goal is to determine the molecular mechanisms and physiological consequences of crosstalk between erbB and Met, beginning with evaluating how the dynamic and stochastic behavior of protein-protein interactions influences signal propagation. Through experiments in live cells and animals engrafted with human ovarian or colon tumor cells, we will determine how erbB and Met crosstalk controls cell fate, tumor growth and drug responses. This interdisciplinary project brings together a team of cell biologists, biophysicists, cancer biologists, biochemists and mathematical modelers, reflecting the strengths of the NM Center for Spatiotemporal Modeling. The proposed work will provide information on protein interactions, signaling pathway integration and physiological outcome. Since aberrant erbB/Met signaling has been implicated in a number of cancers, we expect that this information will open new avenues for combination therapies that target receptor crosstalk.

项目2：阐明erbB/Met家族串扰的机制和后果 Diane Lidke总结，项目PI 这个项目的重点是受体酪氨酸激酶（RTK）之间的串扰，触发细胞内信号 级联并控制重要的细胞过程。我们将应用最先进的显微镜（单分子， 单细胞和体内）与生化测定和数学建模-跨越五个空间尺度-以 提供了一个全面的图片受体串扰如何调节细胞反应。我们的目标受体是 erbB和Met RTK家族成员，在肿瘤发生、转移和药物治疗中具有重要作用。 阻力我们的目标是确定串扰的分子机制和生理后果 erbB和Met之间的关系，从评估蛋白质-蛋白质之间的动态和随机行为开始， 相互作用影响信号传播。通过在活细胞和动物身上进行的实验， 卵巢或结肠肿瘤细胞，我们将确定erbB和Met串扰如何控制细胞命运，肿瘤生长和 药物反应。这个跨学科的项目汇集了一个团队的细胞生物学家，生物药理学家，癌症 生物学家，生物化学家和数学建模者，反映了NM中心的优势， 时空建模拟议的工作将提供有关蛋白质相互作用，信号转导， 途径整合和生理结果。由于异常的erbB/Met信号转导与肿瘤的发生有关， 许多癌症，我们希望这一信息将开辟新的途径，联合治疗的目标， 接收器串音