Project 3

项目3

• 批准号: 7921945
• 负责人: herbert levine
• 金额: $ 16.08万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7921945
• 关键词: Address; Adenylate Cyclase; Behavior; Biological; Biology; Cell Count; Cells; Chemotaxis; Complex; Computer Assisted; Computer Simulation; Computers; Congenital Abnormality; Coupled; Coupling; Cyclic AMP; Cyclic AMP Receptors; Cyclic AMP-Dependent Protein Kinases; Cytoskeleton; Development; Dictyostelium; Dictyostelium discoideum; Embryonic Development; Environment; Event; Evolution; Food; Frequencies; Genes; Lead; Measurement; Methods; Microfluidics; Mitogen-Activated Protein Kinases; Modeling; Molecular; Movement; Mutation; Neoplasm Metastasis; Organism; Organogenesis; Periodicity; Phase; Physiologic pulse; Play; Population; Process; Role; Series; Shapes; Signal Transduction; Source; Staging; System; Testing; Time; Translating; Variant; Vertebrates; Video Recording; Work; Wound Healing; base; cell motility; cell type; mutant; phosphoric diester hydrolase; research study; response

The events studied in Projects 1 and 2 are essential prerequisites for the actual movement of cells towards the source of cAMP. Translocation of the cells allows them to aggregate into groups of up to 105 cells and proceed through multicellular development. Cell movement is an essential process in many multicellular organisms. In vertebrates it plays essential roles in embryogenesis, organogenesis, wound healing and, when aberrant, can lead to birth defects and cancer metastasis (Baggiolini, 1998; Behar et al., 1994; Clark, 1996; Condeelis et al., 2005; Dormann and Weijer, 2003; Muller et al., 2001). Dictyostelium cells are highly motile even while growing as they search for food. The rate of cell movement increases to a peak during the aggregation stage when they signal each other with periodic pulses of cAMP. We have recently shown that a molecular circuit involving the cAMP receptor, adenylyl cyclase, cAMP phosphodiesterase, MAP kinase and PKA generates spontaneous oscillations in cAMP synthesis (Laub and Loomis, 1998). We also have evidence that many of these components are essential for chemotaxis in a natural wave (Maeda et al., 2004; Stepanovic et al., 2005; Wessels et al., 2004; Zhang et al., 2003). Our working hypothesis is that the circuit is coupled to cell movement such that signaling and response are always in phase (Loomis, 2007). Dictyostelium cells provide an excellent test system to further understand the basic biology of cell motility, which appears to have been conserved during evolution leading to vertebrates. In Project 3, we will focus on several aspects of the chemotactic response to temporal and spatial aspects of cAMP waves that leads to aggregation. We will be able to benefit from the expertise we have developed in controlling the cAMP environment within microfluidic devises and the computer assisted quantification of instantaneous velocity of a large number of cells. Three specific aims will be addressed in Project 3.

项目1和2中研究的事件是细胞实际移动的重要前提条件 走向营地。细胞的易位使它们可以汇总为多达105个单元的组 并通过多细胞开发进行。细胞运动是许多多细胞的重要过程 有机体。在脊椎动物中，它在胚胎发生，器官发生，伤口愈合以及，当 异常会导致出生缺陷和癌症转移（Baggiolini，1998； Behar等，1994； Clark，1996； Condeelis等，2005； Dormann和Weijer，2003年； Muller等，2001）。 dictyostelium细胞高度流动性 即使在寻找食物时成长。细胞运动的速率增加到峰值 当他们用周期性脉冲彼此发信号时，聚集阶段。我们最近表明了 涉及cAMP受体，腺苷酸环化酶，磷酸二酯酶，MAP激酶的分子电路 PKA在cAMP合成中产生自发的振荡（Laub和Loomis，1998）。我们也有证据 这些成分中的许多对于自然波中的趋化性至关重要（Maeda等，2004； Stepanovic 等，2005； Wessels等，2004； Zhang等，2003）。我们的工作假设是电路耦合到 细胞运动使信号传导和响应始终处于相位（Loomis，2007）。 dictyostelium细胞 提供出色的测试系统，以进一步了解细胞运动的基本生物学，这似乎具有 在进化过程中得到保守，导致脊椎动物。在项目3中，我们将重点介绍 对cAMP波的时间和空间方面的趋化反应，导致聚集。我们会的 能够从我们在微流体内控制营地环境方面发展的专业知识受益 设计和计算机协助定量大量细胞的瞬时速度。三 项目3将解决具体目标。