Control of Electrostatic Interactions in Complex Biological Systems

复杂生物系统中静电相互作用的控制

• 批准号: 1019626
• 负责人: Gerard Wong
• 金额: $ 33.63万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-11-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1019626&HistoricalAwards=false
• 关键词: Control; Electrostatic; Interactions; Complex; Biological

ID: MPS/DMR/BMAT(7623) 0804363 PI: Wong, Gerard ORG: University of IllinoisTitle: Control of Electrostatic Interactions in Complex Biological SystemsINTELLECTUAL MERIT: This research program aims to use recently developed knowledge of electrostatics in aqueous media to understand and control complex biological systems governed by a hierarchy of interactions, of which electrostatics is only one part. The aim is to go beyond academic, prototypical electrostatic problems, and engage outstanding unsolved problems in biology. In biological systems, electrostatics coexists with other interactions such as the hydrophobic effect, hydrogen bonding, and geometric/osmotic effects. The proposal addresses three unsolved problems for which such hybrid interactions are essential. First is the formation of complexes of antimicrobial proteins (i.e., lysozyme) with oppositely charged polyelectrolyte (i.e., F-actin) to understand and then control the tendency to form stable complexes. In addition to its potential for biomedical impact, this study is motivated by basic questions about the interactions between periodic charge-densities with different periodicities. Second is a set of X-ray studies of mixtures of model lipid vesicles and pore-inducing TAT (trans-acting activator of transcription) proteins. This section will include studies of the particular role of the positively charged amino acids arginine vs lysine (which seems to go beyond the role of electrostatics to some other mechanism) and include exploratory studies on the ability of TAT to carry cargo across a membrane. The third major activity is a study of synthetic pore-forming antimicrobial compounds synthesized by a collaborator at the University of Massachusetts. X-ray scattering will be used to measure pore structure as a function of concentrations in model membranes and the results will be compared to bacterial response for different variants of the antimicrobial compound.BROADER IMPACTS: Most interactions of biological macromolecules involve forces of several types. The proposal attempts to understand the resultant effect of these hybrid forces in complex systems. The mode of action of membrane pore forming peptides, especially the antimicrobial peptides, is not yet understood. This project seeks fundamental understanding of how naturally occurring and synthetic antimicrobial peptides and other membrane pore formers work. The project provides for highly interdisciplinary training of students and postdoctorals who will gain experience not only in the basic physics and physical chemistry of biological systems but who will also become familiar with the resources of national and international light source facilities. The PI has an excellent record of involving undergraduates in his research program, many of whom are coauthors on publications. He plans to continue to host undergraduate researchers and to give these students the opportunity to experience a research environment that leads many to continue on a research pathway in graduate and professional school. The PI is anxious to expand his outreach activity to the K-12 educational sector beyond the typical "one-shot" university Open House programs and to develop a more enduring relationship with K-12 students and teachers. To this end he has established a partnership with a local middle school, and he will make repeated visits to the school with the goal of "making the strange familiar and the familiar strange" through a series of presentations and activities that give the students and teachers hands-on experience with the properties of interesting materials.

ID：MPS/DMR/BMAT（7623）0804363 PI：Wong，Gerard ORG：University of Illinois伊利诺伊大学在复杂的生物系统中控制静电相互作用智力优势：这项研究计划的目的是利用最近开发的知识静电在水介质中理解和控制复杂的生物系统所管辖的层次结构的相互作用，其中静电只是一部分。 其目的是超越学术，原型静电问题，并从事生物学中悬而未决的问题。在生物系统中，静电与其他相互作用共存，如疏水效应，氢键和几何/渗透效应。 该提案解决了三个未解决的问题，这种混合互动是必不可少的。首先是抗微生物蛋白复合物的形成（即，溶菌酶）与带相反电荷的酶（即，F-肌动蛋白）来理解并控制形成稳定复合物的趋势。除了其潜在的生物医学影响外，这项研究的动机是关于具有不同周期性的周期性电荷密度之间相互作用的基本问题。 第二个是一组X射线研究模型脂质囊泡和孔诱导达特（反式作用转录激活因子）蛋白的混合物。本节将包括带正电荷的氨基酸精氨酸与赖氨酸的特殊作用的研究（这似乎超出了静电作用的一些其他机制），并包括达特携带货物跨膜能力的探索性研究。第三项主要活动是研究由马萨诸塞州大学的合作者合成的合成成孔抗菌化合物。 X-射线散射将被用来测量作为模型膜中的浓度的函数的孔结构，并且将结果与针对抗微生物化合物的不同变体的细菌响应进行比较。 该提案试图了解这些混合力在复杂系统中的合成效果。 膜孔形成肽，特别是抗微生物肽的作用方式尚未了解。 该项目旨在从根本上了解天然存在的和合成的抗菌肽和其他膜成孔剂是如何工作的。 该项目为学生和博士后提供高度跨学科的培训，他们不仅将获得生物系统的基础物理和物理化学方面的经验，而且还将熟悉国家和国际光源设施的资源。 PI在让本科生参与其研究项目方面有着出色的记录，其中许多人是出版物的合著者。他计划继续接待本科研究人员，并让这些学生有机会体验一个研究环境，导致许多人继续在研究生和专业学校的研究途径。PI渴望将他的外展活动扩展到K-12教育部门，超越典型的“一次性”大学开放日计划，并与K-12学生和教师建立更持久的关系。 为此，他与当地一所中学建立了合作伙伴关系，并将多次访问学校，通过一系列的演讲和活动，让学生和教师亲身体验有趣材料的特性，以“使陌生的熟悉和熟悉的陌生”为目标。