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: 8146018
• 负责人: Sarah L Veatch
• 金额: $ 24.65万
• 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/8146018
• 关键词: Antigens; Area; Award; B-Lymphocytes; Biological; Cell Signaling Process; Cell membrane; Cell physiology; Cell surface; Cells; Collaborations; Data; Development; Electron Microscopy; Emerging Technologies; Faculty; Foundations; Future; Generic Drugs; Genetic; Goals; Heterogeneity; IgE; Immune; Instruction; Intervention; Laboratories; Lateral; Lead; Life; Lipids; Liquid substance; Maintenance; Measurement; Mediating; Membrane; Mentors; Methodology; Methods; Microscope; Normal Cell; Pathology; Pathway interactions; Phase Transition; Physiological; Play; Positioning Attribute; Process; Property; Proteins; Research; Research Personnel; Resolution; Resources; Role; Signal Pathway; Signal Transduction; Staging; Structure; System; T-Lymphocyte; Techniques; Temperature; Testing; Theoretical model; Training; Transition Temperature; Universities; Vesicle; Work; base; cell fixing; cell type; functional outcomes; human disease; knock-down; mast cell; membrane model; nanoscale; novel; physical state; programs; research study; simulation; submicron; success; tool

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.

我的proposecJ研究的目标是描述细胞质膜中脂质介导的横向组织，并破译产生这种结构的潜在物理机制。在这样做的过程中，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，从而克服细胞膜研究目前面临的重大障碍。我过去在简单模型膜中破译液体不可渗透性的成功为我的研究奠定了基础。 生物膜的研究现状和未来在我早期在康奈尔大学贝尔德实验室的博士后工作中，我发现了从RBL肥大细胞中分离的质膜囊泡的强烈临界波动。这一结果有力地支持了我的工作假设，即在生理温度下细胞质膜中存在临界波动。在这个奖项的指导阶段，我已经实施了 实验和分析技术，以量化和解释完整的细胞表面上的纳米尺寸的组织（目标1），我已经研究了质膜的组成和结构的IgE介导的信号通路在RBL肥大细胞（目标2）的功能影响。通过这些研究，我成功地将这种定量和生物药理学动机的方法应用于这个生物医学相关的研究领域。作为一个独立的研究者，我将继续这两个目标的工作，最终破译 膜横向组织的物理基础（目标1），并开发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横向异质性的功能后果（目标2）。我的长期目标是开发通用方法来探测脂质在广泛的过程和细胞类型中的功能作用，这将使新的研究路线进入脂质介导的细胞质膜组织的生物医学后果。通往独立之路 奖给了我的独立性，专注于我的生物学培训在我的博士后岁月，并顺利过渡到我目前的独立教师职位的资源。