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

项目2：阐明erbB/Met家族串扰的机制和后果 Diane Lidke摘要，《项目PI》 该项目的重点是触发细胞内信号的受体酪氨酸激酶(RTK)之间的串扰。 级联和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)通过生化分析和数学建模--跨越五个空间尺度--来 全面介绍受体串扰是如何调节细胞反应的。我们的目标受体是 Erb B和Met RTK家族成员，在肿瘤发生、转移和药物中起重要作用 抵抗。我们的目标是确定串扰的分子机制和生理后果 在erbB和Met之间，从评估蛋白质-蛋白质的动态和随机行为开始 相互作用会影响信号的传播。通过对植入人类的活细胞和动物进行实验 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由细胞生物学家、生物物理学家、癌症 生物学家、生物化学家和数学模型师，反映了NM中心的优势 时空建模。拟议的工作将提供关于蛋白质相互作用、信号转导的信息 通路整合和生理结果。因为异常的erbB/Met信号与一种 癌症的数量，我们预计这一信息将为靶向的联合疗法开辟新的途径 接收器串扰。

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.