RUI: Dynamics, Structure and Formation of Polyene Channels

9603582 Hartsel两性霉素B是研究膜离子通道形成和性质的经典模型化合物之一，但该通道的分子结构仍存在争议。我们的目标是利用荧光、吸光度和圆二色谱技术对经多烯天然产物两性霉素B处理的脂质体微囊进行处理，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组织在一起，在细胞脂膜中形成离子渗透孔。然而，通道的大小和性质似乎是不同的，取决于哪种甾醇，麦角甾醇或胆固醇，存在于磷脂膜和渗透胁迫(肿胀)的条件下。简单膜中渗透胁迫的条件将被用来试图以最小的并发症“捕获”独有的活性通道结构(S)。生物膜通道或孔最终是调节基本过程的关键，从神经传递一直到每个细胞对营养物质和废物的基本吸收和消除。这一范围应该会促进我们对多烯通道和膜通道的总体了解。此外，拟议的工作将使本科生大量参与这项工作的各个方面，从实验设计和数据收集，到在科学会议上润色和展示数据，最后在同行评议的期刊上发表。在将本科生研究作为培训理科学生的教学工具方面，P.I.有着丰富的经验和成功的经验。

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.