Mechanistic studies of membrane lateral organization in cell plasma membranes.

细胞质膜膜横向组织的机制研究。

基本信息

批准号：
7659731
负责人：
Sarah L Veatch
金额：
$ 8.99万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2011-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7659731
关键词：
Area Award Behavior Biochemical Biological Cell membrane Cell physiology Cell surface Cells Cholesterol Complex Dependence Development Disease Faculty Foundations Future Genetic Goals Heterogeneity IgE Image Imaging Techniques Intervention Laboratories Lateral Life Lipids Liquid substance Maintenance Mediating Membrane Membrane Proteins Mentors Methodology Methods Normal Cell Nuclear Magnetic Resonance Optics Outcome Pathology Pathway interactions Phase Phase Transition Phospholipid Metabolism Physical Chemistry Physiological Play Positioning Attribute Principal Investigator Process Property Proteins Recycling Research Research Personnel Resolution Resources Role Scanning Electron Microscopy Scientist Signal Pathway Signal Transduction Staging Sterols Structure System Techniques Temperature Testing Thermodynamics Training Transition Temperature Universities Vesicle Work base biological systems cell type design fluorescence imaging genetic manipulation human disease innovation knock-down mast cell member membrane model nanoscale novel protein distribution protein expression protein function research study simulation skills small molecule submicron success theories tool

项目摘要

DESCRIPTION (provided by applicant): The goal of my proposed 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 postdoctoral studies in biological membranes. Since joining the Baird Laboratory at Cornell University, I have 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 will begin to directly test my working hypothesis by implementing experimental and analytic techniques to quantify and interpret nanometer-size organization on the intact cell surface (Aim1). 1 will also develop experimental methods to modulate lateral heterogeneity in both plasma membrane vesicles and intact cell plasma membranes (Aim 2). Through these studies, I will acquire the skills and perspective necessary to successfully apply my strong physical background 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 (Aim1), and developing novel methodologies to probe the functional consequences of lipid-mediated lateral heterogeneity in IgE mediated signaling in RBL mast cells (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 will give me the resources to focus deeply on my biological training in my postdoctoral years, and the independence to pursue my own research objectives as I transition into my future position as a young faculty member. Relevance: It is widely accepted that plasma membrane lateral heterogeniety plays important functional roles in normal cell processes and in the development and maintenance of human diseases. I will open new opportunities for intervention in cell membrane-based pathologies by developing effective experimental techniques and a clear conceptual framework in which to study lipids and proteins in native membranes.

描述（由申请人提供）：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，并破译引起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混溶的成功构成了我当前和将来的生物膜的博士后研究的基础。自从加入康奈尔大学的BAIRD实验室以来，我已经确定了从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，我将通过实施实验和分析技术来直接测试我的工作假设，以量化和解释完整细胞表面上的纳米尺寸组织（AIM1）。 1还将开发实验方法，以调节质膜囊泡和完整细胞质膜的侧向异质性（AIM 2）。通过这些研究，我将获得所需的技能和观点，以成功地将我的强大身体背景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，我将继续针对这两个目标，最终破解了膜横向组织的物理基础（AIM1），并开发了新的方法，以探测RBL肥大细胞中IgE介导的信号传导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。获得独立奖的途径将使我有资源将重点放在博士后几年的生物学培训上，以及在过渡到我作为年轻教职员工的未来地位时追求自己的研究目标的独立性。相关性：广泛接受的是，质膜侧面异源在正常细胞过程以及人类疾病的发展和维持中起着重要的功能作用。我将通过开发有效的实验技术和一个清晰的概念框架来研究基于细胞膜的病理学的新机会，并在本地膜中研究脂质和蛋白质。