CAREER: Molecular Recognition and Biological Function at Water-Bilayer Interfaces: Bridging Structure, Dynamics, and Function in Antimicrobial Peptides

职业：水双层界面的分子识别和生物功能：抗菌肽的桥接结构、动力学和功能

• 批准号: 0832571
• 负责人: Myriam Cotten
• 金额: $ 52.5万
• 依托单位: Hamilton College
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-31 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0832571&HistoricalAwards=false
• 关键词: CAREER; Molecular; Recognition; Biological; Function

With the support of a CAREER award from the Organic and Macromolecular Chemistry Program at the National Science Foundation, Professor Myriam Cotten of Pacific Lutheran University will investigate structure-function-dynamics relationships in amphipathic cationic antimicrobial peptides, important peptides belonging to a large family of biomolecules active at interfaces. The long-term goal is to identify common principles that will facilitate the design of pharmaceuticals with broad-spectrum antibacterial activity, minimum induction of bacterial resistance, and low toxicity to mammalian cells. A bottleneck in this area of research is the lack of atomic level information on peptide-lipid interactions. Professor Cotten's main objective is to characterize the secondary structures and dynamics of selected antimicrobial peptides in the presence of lipids. This knowledge will be used to identify factors optimizing specific molecular interactions, initially at cell membranes, that are directly related to peptide function and mode of action. Biochemical, biophysical, and spectroscopic methods will be used to synthesize and purify selected antimicrobial peptides; and to compare their atomic level structures, molecular interactions with lipids, and dynamics under physiologically-relevant conditions to advance our understanding of molecular recognition, specificity, mode of action, and potency. Piscidins, the selected peptides, will be incorporated in aligned, hydrated lipid bilayers and subjected to solid-state nuclear magnetic resonance techniques. Specific parameters relevant to biological function will be tested.With the support of a CAREER award, interdisciplinary research on important antimicrobial peptides will provide results that will feed a larger body of knowledge aimed at improving our fundamental understanding of how these peptides recognize membranes and initiate their activities on different types of cells. Broader impacts of the proposed activity are primarily the high quality science education which will be offered to a diverse research group. This team will include college and pre-college students from underrepresented groups, a future high school teacher, and a postdoctoral fellow. All project participants will engage in rigorous scientific inquiry and delightful discovery. They will actively contribute to the proposed research, travel to national user facilities equipped with state-of-the-art instrumentation, and present results at local and national meetings. This program will help inspire students for professionally and personally rewarding scientific careers that will contribute to continued vitality of the sciences and workforce.

在美国国家科学基金会有机和大分子化学计划的职业奖的支持下，太平洋路德大学的Myriam Cotten教授将研究两亲性阳离子抗菌肽的结构-功能-动力学关系，这是一个重要的肽，属于一个大家族的生物分子在界面上的活性。 长期目标是确定共同的原则，这将有助于设计具有广谱抗菌活性，最小诱导细菌耐药性和对哺乳动物细胞毒性低的药物。这一研究领域的瓶颈是缺乏肽-脂质相互作用的原子水平信息。 Cotten教授的主要目标是表征脂质存在下所选抗菌肽的二级结构和动力学。这些知识将用于确定优化特定分子相互作用的因素，最初是在细胞膜上，这些因素与肽的功能和作用模式直接相关。生物化学，生物物理学和光谱学方法将用于合成和纯化选定的抗菌肽;并比较它们的原子水平结构，与脂质的分子相互作用，以及生理相关条件下的动力学，以促进我们对分子识别，特异性，作用模式和效力的理解。 鱼肽，选定的肽，将被纳入对齐，水合脂质双层，并进行固态核磁共振技术。在CAREER奖的支持下，对重要抗菌肽的跨学科研究将提供更多的知识，旨在提高我们对这些肽如何识别膜并启动其在不同类型细胞上的活动的基本理解。 拟议活动的更广泛影响主要是向各种研究群体提供高质量的科学教育。该团队将包括来自代表性不足群体的大学和大学预科学生，未来的高中教师和博士后研究员。所有项目参与者都将进行严格的科学探究和令人愉快的发现。他们将积极促进拟议的研究，前往配备最先进仪器的国家用户设施，并在地方和国家会议上介绍结果。该计划将有助于激发学生的专业和个人奖励的科学事业，这将有助于科学和劳动力的持续活力。

项目成果

Can antimicrobial peptides scavenge around a cell in less than a second?

• DOI: 10.1016/j.bbamem.2009.08.018
• 发表时间: 2010-02-01
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
• 影响因子: 3.4
• 作者: Chekmenev, Eduard Y.;Vollmar, Breanna S.;Cotten, Myriam
• 通讯作者: Cotten, Myriam