IDBR: Development of a Spectroscopic Instrument for the Study of Vibrational Relaxation and Local Motion in Biomolecular Systems

IDBR：开发用于研究生物分子系统中振动弛豫和局部运动的光谱仪器

• 批准号: 1062419
• 负责人: Gary Blanchard
• 金额: $ 27.51万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1062419&HistoricalAwards=false
• 关键词: IDBR; Development; Spectroscopic; Instrument; Study

AbstractThis proposal is for the construction of an instrument that will provide previously unobtainable information on the organization and dynamics of plasma membranes, biomimetic structures, and light harvesting proteins. The dissipation of energy within lipid bilayers and light harvesting proteins is not well understood but is thought to mediate the function of these two different classes of biomolecular systems. One of the broad biological issues this project addresses is the fundamental, molecular basis for the formation of lipid raft structures, and why such structures vary with the concentrations and identities of the bilayer constituents. Understanding the molecular structural basis for lipid raft organization requires that the viscoelastic properties and intermolecular interactions of the lipid bilayer constituents can be measured. The proposed instrumentation will allow for the measurement of molecular motion and thermal energy flow in biomolecular systems. This project entails designing, constructing, and characterizing an instrument that will apply stimulated-emission spectroscopy to the study of structure and dynamics of biological membranes and proteins. The instrument will reveal how the lipid and protein components of the mammalian cell membrane interact to yield functional assemblies that are responsible for energy transduction, transmembrane transport, and molecular recognition. The instrument will characterize the lipid-lipid and lipid-protein interactions that control the fluidity of the lipid bilayer assembly and the flow of thermal energy between components that serves as the driving force for chemical reactions and molecular motion.The instrument will employ tunable picosecond lasers in a two-color pump?probe detection scheme to examine vibrational energy-transfer and fast molecular-scale motions in bilayer membranes and light harvesting proteins. Such measurements have not been possible before. The detection system is phase-sensitive and shot-noise-limited to measure transmission changes of one part in 107. Because the reaction dynamics underlying the formation and decay of short-lived complexes in membranes are controlled by vibrationally activated barrier-crossing processes, the information obtained with the proposed instrument is crucial to reaching an understanding of the dynamics associated with spatially heterogeneous structures, including lipid rafts and proteins. The creation of broadly accessible instrumentation that advances the state of the art in the measurement of lipid bilayer properties and dynamics will have a major impact on the MSU and regional scientific communities as well as on the global scientific community. The PI and co-PIs collaborate with faculty in a host of other MSU departments (e.g. Biochemistry and Molecular Biology, Food Safety and Toxicology, Cell and Molecular Biology, Microbiology and Molecular Genetics), faculty from nearby institutions (e.g. Saginaw Valley State University, Western Michigan University) and from international institutions (e.g. University of Warsaw (Poland), University of Bath (UK), National University of Singapore, and Shaanxi Normal University (PRC)). They also collaborate with Federal research organizations such as the US Army Engineer Research and Development Center in Champaign, IL. Broadening inclusion of under-represented groups in science is critically important. Michigan State University has multiple programs in place to connect with under-represented groups at the high school (MSU High School Honors Science/Math/Engineering Program (HSHSP), ACS Project SEED), undergraduate (National Organization of Black Chemists and Chemical Engineers (NOBCChE), DREW/TAC Program), graduate (NOBCChE, MSU African-American, Latino(a)/Chicano(a), Asian/Pacific American, and Native American (ALANA) Program) and post-graduate levels (MSU sponsored minority post-doctoral fellowships). The PI and the co-PIs have collaborated with these programs on several levels and continue to strive to provide students from all groups with hands-on research opportunities and mentoring.

摘要该提案旨在建造一种仪器，该仪器将提供以前无法获得的有关质膜、仿生结构和光捕获蛋白质的组织和动力学的信息。 脂质双层和光捕获蛋白内的能量耗散尚不清楚，但被认为介导了这两类不同类别的生物分子系统的功能。 该项目解决的广泛生物学问题之一是脂筏结构形成的基本分子基础，以及为什么这种结构随着双层成分的浓度和特性而变化。 了解脂筏组织的分子结构基础需要测量脂双层成分的粘弹性特性和分子间相互作用。 所提出的仪器将允许测量生物分子系统中的分子运动和热能流。该项目需要设计、构建和表征一种仪器，该仪器将应用受激发射光谱学来研究生物膜和蛋白质的结构和动力学。 该仪器将揭示哺乳动物细胞膜的脂质和蛋白质成分如何相互作用，产生负责能量转导、跨膜运输和分子识别的功能组件。 该仪器将表征脂质-脂质和脂质-蛋白质相互作用，这些相互作用控制脂质双层组件的流动性以及作为化学反应和分子运动驱动力的组分之间的热能流动。该仪器将在双色泵浦探针检测方案中采用可调谐皮秒激光器来检查双层中的振动能量传递和快速分子尺度运动 膜和光捕获蛋白。 这样的测量以前是不可能的。 该检测系统具有相敏性和散粒噪声限制，可测量 107 中某一部分的传输变化。由于膜中短命复合物形成和衰变的反应动力学是由振动激活的跨越障碍过程控制的，因此使用所提出的仪器获得的信息对于了解与空间异质结构相关的动力学至关重要，包括脂筏和 蛋白质。创建可广泛使用的仪器，推进脂质双层特性和动力学测量的最先进技术，将对密歇根州立大学和地区科学界以及全球科学界产生重大影响。 PI 和 co-PI 与密歇根州立大学其他许多系（例如生物化学和分子生物学、食品安全和毒理学、细胞和分子生物学、微生物学和分子遗传学）的教职人员、附近机构（例如萨吉诺谷州立大学、西密歇根大学）和国际机构（例如华沙大学（波兰）、巴斯大学）的教职人员合作 （英国）、新加坡国立大学和陕西师范大学（中国））。 他们还与联邦研究组织合作，例如位于伊利诺伊州尚佩恩的美国陆军工程师研究与开发中心。扩大科学领域代表性不足群体的包容性至关重要。 密歇根州立大学设有多个项目来与高中的弱势群体建立联系（MSU 高中荣誉科学/数学/工程项目 (HSHSP)、ACS 项目 SEED）、本科生（全国黑人化学家和化学工程师组织 (NOBCChE)、DREW/TAC 项目）、研究生（NOBCChE、MSU 非裔美国人、拉丁裔 (a)/奇卡诺 (a)、亚裔/太平洋裔美国人、 和美洲原住民 (ALANA) 计划）和研究生水平（密歇根州立大学赞助的少数族裔博士后奖学金）。 PI 和 co-PI 与这些项目进行了多个层面的合作，并继续努力为所有群体的学生提供实践研究机会和指导。