Mechanistic studies of membrane lateral organization in cell plasma membranes.

细胞质膜膜横向组织的机制研究。

• 批准号: 8133576
• 负责人: Sarah L Veatch
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8133576
• 关键词: Cell membrane; Cells; Lateral; Membrane

The goal of my proposecJ research is to characterize lipid-mediated lateral organization in cell plasma membranes and to decipher the underlying physical mechanisms that give rise to this structure. In so doing, I will surmount significant barriers currently facing cell membrane research by developing new experimental tools to manipulate and test the functional consequences of lipid-mediated organization in living cells. My past success in deciphering liquid immiscibility in simple model membranes forms the foundation for my current and future studies in biological membranes. In my early postdoctoral work with Baird Laboratory at Cornell University, I identified robust critical fluctuations in plasma membrane vesicles isolated from RBL mast cells. This result strongly supports my working hypothesis that critical fluctuations are present in cell plasma membranes at physiological temperatures. In the mentored stage of this award, I have implemented experimental and analytic techniques to quantify and interpret nanometer-size organization on the intact cell surface (Aim 1), and I have investigated the functional effects of plasma membrane composition and structure on the IgE-mediated signaling pathway in RBL mast cells (Aim 2). Through these studies, I successfully applied this quantitative and biophysically motivated approach to this biomedically relevant area of research. As an independent researcher, I will continue work on both aims, eventually deciphering the physical basis of membrane lateral organization (Aim 1), and developing novel methodologies to probe the functional consequences of lipid-mediated lateral heterogeneity in antigen induced immune cell signaling processes (Aim 2). My long term goal is develop general methods to probe the functional roles of lipids in a wide range of processes and cell types which will enable new lines of study into the biomedical consequences of lipid mediated plasma membrane organization in cells. The Pathway to Independence Award has given me the independence to focus deeply on my biological training in my postdoctoral years, and the resources to smoothly transition into my current independent faculty position.

我提出的研究的目的是表征细胞质膜中脂质介导的侧面组织，并破译产生这种结构的基本物理机制。这样，我将通过开发新的实验工具来操纵和测试活细胞中脂质介导的组织的功能后果，从而克服目前面临细胞膜研究的重大障碍。我过去在简单模型膜上破译液体不可药用方面的成功构成了我的基础 当前和未来的生物膜研究。在我在康奈尔大学（Cornell University）的Baird实验室的早期博士后工作中，我确定了从RBL肥大细胞分离的质膜囊泡中的强大关键波动。该结果强烈支持我的工作假设，即生理温度下的细胞质膜中存在关键波动。在该奖项的指导阶段，我已经实施了 实验和分析技术以量化和解释完整细胞表面上的纳米大小组织（AIM 1），我研究了质膜组成和结构对RBL肥大细胞中IgE介导的信号通路的功能效应（AIM 2）。通过这些研究，我成功地将这种定量和生物物理动机的方法应用于这一与生物医学相关的研究领域。作为一名独立的研究人员，我将继续以两个目标进行工作，最终破译 膜侧组织​​的物理基础（AIM 1），并开发了新的方法来探测抗原诱导的免疫细胞信号传导过程中脂质介导的侧向异质性的功能后果（AIM 2）。我的长期目标是开发一般方法，以探测脂质在各种过程和细胞类型中的功能作用，这将使新的研究线研究细胞中脂质介导的质膜组织的生物医学后果。独立之路 奖项使我具有独立性的重点，重点是我的博士后几年的生物学培训，以及顺利过渡到我目前的独立教师职位的资源。