Control of Electrostatic Interactions in Complex Biological Systems

ID：MPS/DMR/BMAT(7623)0804363 PI：Wong，Gerard ORG：伊利诺伊大学题目：复杂生物系统中静电相互作用的控制研究优点：这项研究计划旨在利用最近发展起来的水介质中的静电学知识来了解和控制由相互作用层次控制的复杂生物系统，静电学只是其中的一部分。其目的是超越学术的、典型的静电问题，并致力于生物学中尚未解决的突出问题。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。该提案解决了三个尚未解决的问题，对于这些问题，这种混合互动是必不可少的。首先是抗菌蛋白(即溶菌酶)与带相反电荷的聚电解质(即F-肌动蛋白)形成的复合体，以了解并控制形成稳定复合体的趋势。除了其潜在的生物医学影响，这项研究的动机是关于不同周期的周期性电荷密度之间的相互作用的基本问题。第二个是对模型脂泡和诱导孔洞的TAT(反式作用转录激活剂)蛋白混合物的X射线研究。这一部分将包括带正电的氨基酸精氨酸和赖氨酸的特殊作用的研究(这似乎超越了静电的作用和一些其他机制)，并包括关于TAT携带货物通过膜的能力的探索性研究。第三个主要活动是由马萨诸塞大学的合作者合成的合成成孔抗菌化合物的研究。X射线散射将用于测量孔结构作为模型膜中浓度的函数，并将结果与细菌对不同种类的抗菌化合物的反应进行比较。BROADER影响：大多数生物大分子的相互作用涉及几种类型的力。该提案试图理解这些混合力在复杂系统中的综合效应。膜成孔肽，尤其是抗菌肽的作用机制尚不清楚。这个项目试图从根本上理解天然的和人工合成的抗菌肽和其他膜造孔剂的工作原理。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本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在让本科生参与他的研究项目方面有很好的记录，其中许多人是出版物的合著者。他计划继续接待本科生研究人员，并让这些学生有机会体验一种研究环境，让许多人在研究生和专业学校继续走上研究之路。PI急于将他的外展活动扩展到K-12教育部门，超越典型的“一次性”大学开放参观计划，并与K-12学生和教师发展更持久的关系。为此，他与当地一所中学建立了合作伙伴关系，他将反复访问学校，目标是通过一系列的演讲和活动，让学生和老师亲身体验有趣的材料的属性，目的是让陌生的东西熟悉，熟悉的东西陌生。

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.