RUI: Dynamics, Structure and Formation of Polyene Channels

RUI：多烯通道的动力学、结构和形成

• 批准号: 9603582
• 负责人: Scott Hartsel
• 金额: $ 21.82万
• 依托单位: University of Wisconsin-Eau Claire
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9603582&HistoricalAwards=false
• 关键词: RUI; Dynamics; Structure; Formation; Polyene

9603582 Hartsel Amphotericin B is one of the classic model compounds to study membrane ion channel formation and properties, but the molecular structure of the channel is still controversial. The goal is to use fluorescence, absorbance and circular dichroism techniques to liposomal membrane vesicles treated with the polyene natural product Amphotericin B to uncover the molecular structure and kinetics of this membrane channel-forming compound. Many polyenes may form ion permeable pores in cellular lipid membranes by organizing molecules with the polar polyalcohol region in the middle. However, the size and nature of the channels seem to vary depending upon which sterol, ergosterol or cholesterol, is present in the phospholipid membrane and under conditions of osmotic stress (swelling). The condition of osmotic stress in simple membranes will be used in an attempt to "trap" the exclusive active channel structure(s) with a minimum of complications. Biological membrane channels or pores are ultimately the key to regulating fundamental processes from neurotransmission all the way to basic uptake of and elimination of nutrients and wastes in every cell. This reach should advance our knowledge of polyene channels and membrane channels in general. In addition, the proposed work will heavily involve undergraduate students in carrying out every aspect of the work, from experimental design and collection of data through polishing and presenting the data at scientific conferences and ultimately publication in peer-reviewed journals. The P.I. has had extensive experience and success in using undergraduate research as a pedagogical tool for training of science students.

9603582 Hartsel Amphotericin B是研究膜离子通道形成和性质的经典模型化合物之一，但通道的分子结构仍存在争议。 目标是利用荧光、吸光度和圆二色性技术对经多烯天然产物两性霉素 B 处理的脂质体膜囊泡进行分析，以揭示这种膜通道形成化合物的分子结构和动力学。 许多多烯可以通过将分子与中间的极性多元醇区域组织起来，在细胞脂质膜中形成离子可渗透的孔。 然而，通道的大小和性质似乎根据磷脂膜中存在的甾醇、麦角甾醇或胆固醇以及渗透压（膨胀）条件而变化。 简单膜中的渗透应力条件将用于尝试以最小的并发症“捕获”专有的活性通道结构。 生物膜通道或孔最终是调节从神经传递一直到每个细胞中营养物质和废物的基本吸收和消除的基本过程的关键。 这一成果应该会增进我们对多烯通道和膜通道的了解。 此外，拟议的工作将大量让本科生参与工作的各个方面，从实验设计和数据收集，到在科学会议上完善和展示数据，最后在同行评审期刊上发表。 P.I.在利用本科生研究作为培养理科学生的教学工具方面拥有丰富的经验和成功。