CAREER: Biological tuning of plasma membrane mixing

所有动物细胞的外表面都包裹着一层质膜。细胞控制其质膜的蛋白质和脂质组成，以支持广泛的功能，包括作为局部细胞环境的传感器。例如，质膜感知并与细胞内部沟通何时适合生长和分裂，细胞是否应该爬行以及在何处爬行，或者当附近存在某些化合物或化合物类别时。该项目将研究细胞如何以及为什么适应其质膜组成以响应其生长条件的几种变化。许多这些传感功能被认为取决于蛋白质和脂质如何在质膜内组织，研究人员将研究当细胞调整膜组成时，膜非均质性和传感功能是如何受到影响的。该项目的长期目标是发现细胞如何维持异质膜，以及这种膜结构如何有助于细胞的有效功能。研究人员将通过出版物、会议报告、公开演讲、开发本科课程以及向来自物理科学背景不足的高中生推广他们的发现。首席研究员将培训本科生和研究生在STEM领域的职业生涯。从完整细胞中分离出来的质膜在室温下冷却时，会分成两种液相，类似于三维的油和水。在低温下这种相变的存在预示着在细胞生长的较高温度下存在较小的膜结构域。本研究的目的是在生长温度下直接观察完整细胞中的结构域，并确定细胞是否通过调整其膜组成来控制这些结构域的物理性质，从而优化细胞功能。这项研究将使用传统的细胞生物学、生物化学和生物物理学技术，以及尖端的实验方法，包括超分辨率荧光定位显微镜对膜成分的纳米级组织进行成像，以及定量脂质组学来详细描述质膜脂质的组成。

All animal cells are surrounded by a plasma membrane that defines the outer surface of the cell. Cells control the protein and lipid composition of their plasma membrane to support a broad range of functions, including acting as a sensor of the local cellular environment. For example, the plasma membrane senses and communicates to the cell interior when it is appropriate to grow and divide, if and where the cell should crawl, or when certain compounds or classes of compounds are present in the vicinity. This project will investigate how and why cells adapt their plasma membrane composition in response to several changes in their growth conditions. Many of these sensing functions are thought to depend on how proteins and lipids are organized within the plasma membrane, and the researchers will investigate how both membrane heterogeneity and sensing functions are impacted as cells adjust membrane composition. The long term goals of the project are to discover how cells maintain a heterogeneous membrane, and how this membrane structure contributes to the efficient functioning of the cell. The researchers will communicate their findings through publications, conference presentations, public lectures, development of undergraduate curricula, and outreach to high school students from backgrounds that are under-represented in the physical sciences. The principle investigator will train undergraduate and graduate students for careers in STEM fields.Plasma membranes isolated from intact cells separate into two liquid phases when cooled below room temperature, similar to oil and water in three dimensions. The presence of this phase transition at low temperature predicts the existence of smaller membrane domains at the higher temperatures where cells live in culture. The objective of the research is to directly observe domains in intact cells at growth temperature, and to determine if cells tune their membrane composition to control the physical properties of these domains in order to optimize cellular functions. The research will use conventional cell biological, biochemical, and biophysical techniques as well as cutting edge experimental methods, including super-resolution fluorescence localization microscopy to image the nano-scale organization of membrane components and quantitative lipidomics to detail plasma membrane lipid composition.