Biophysical Measurements of Lipid Membranes to Investigate Miscibility, Critical Points, and Sterol Solubility

膜中的脂质通过分离成具有与周围膜不同的组成的液体域来响应温度或整体膜组成的特定变化。此外，双层膜的一个小叶中的脂质与相对小叶中的脂质如此强烈地相互作用，以至于即使在不存在膜蛋白的情况下，也会从膜的一侧到另一侧诱导结构域。该项目将探索脂质双层所执行的复杂功能，最终目标是塑造我们对细胞膜物理行为的认识，并指导生物学家采用新方法来理解复杂的生物系统。解决这些问题的主要工具将是荧光显微镜和NMR。 为了研究瓣叶间相互作用和跨膜瓣叶的域诱导，将检测从膜的一个瓣叶到另一个瓣叶的液体域诱导机制。为了研究脂质分布相对于整体相行为的局部变化，将评价膜组分交联对膜相行为的影响。为了研究固醇溶解度，将采用NMR。为了研究在细胞膜的内叶中含有脂质（PE脂质、PS脂质、PI脂质）的膜是否形成液域，将制作含有这些脂质的囊泡并进行分析。PI将直接向本科生和研究生提供建议，并在全国科学会议上展示研究结果。凯勒实验室的大多数研究生都是女性。凯勒将继续改进她开发的课堂资源，如数学教程，向学生介绍研究研讨会和文献检索的作业，以及强调当前研究主题的课堂内容。凯勒博士最近因其在课堂上的成就而获得了2005年华盛顿大学化学系杰出教学奖和2006年华盛顿大学杰出教学奖。凯勒博士将继续通过向UW Faculty Connections学生，UW本科生研究协会，UW化学学生协会，UW纳米技术学生协会和UW博士后协会介绍来参与UW指导活动。在周边社区，凯勒博士将继续致力于实施一个集中的，可搜索的校园研讨会网络列表，使当地行业和社区成员能够了解华盛顿大学的相关科学研究。凯勒博士将继续传播她开发的材料，以指导美国各地的年轻教师。

Lipids in a membrane respond to particular changes in temperature or overall membrane composition by segregating into liquid domains with compositions that are distinct from the surrounding membrane. Furthermore, lipids in one leaflet of a bilayer membrane interact so strongly with lipids in the opposite leaflet that domains are induced from one side of a membrane to the other, even in the absence of membrane proteins. This project will probe the complex functions performed by lipid bilayers, with the eventual goal of shaping our knowledge of the physical behaviors accessible to cell membranes, and guiding biologists in new approaches to understanding complex biological systems. The primary tools of approaching these problems will be fluorescence microscopy and NMR. To investigate Inter-leaflet interactions and induction of domains across membrane leaflets, mechanisms of induction of liquid domains from one leaflet of a membrane to the other will be tested. To investigate local changes in lipid distributions versus global phase behavior, the effect of crosslinking of membrane components on membrane phase behavior will be evaluated. To study sterol solubility, NMR will be employed. To investigate whether liquid domains form in membranes containing lipids found in the inner leaflet of cell membranes (PE lipids, PS lipids, and PI lipids), vesicles containing those lipids will be produced and analyzed.The PI will directly advise undergraduate and graduate researchers and they will present their research results at national scientific meetings. The majority of graduate students in the Keller laboratory have been women. In the classroom, Dr. Keller will continue to improve the classroom resources she has developed such as a mathematics tutorial, an assignment that introduces students to research seminars and literature searches, and classroom content that emphasizes current research topics. Dr. Keller has recently been recognized for her accomplishments in the classroom with a UW Department of Chemistry Outstanding Teaching Award in 2005, and a University of Washington Distinguished Teaching Award in 2006. In the UW community, Dr. Keller will continue to participate in UW mentoring activities through presentations to the UW Faculty Connections students, the UW Undergraduate Research Society, the UW Chemistry Student Association, the UW Nanotech Student Association, and the UW Postdoctoral Association. In the surrounding community, Dr. Keller will continue to work to implement a centralized, searchable web listing of seminars on campus to enable local industry and community members to learn about relevant scientific research at the University of Washington. Dr. Keller will continue to disseminate materials that she has developed in order to mentor young faculty across the U.S.