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

AbstractThis建议是建设一个仪器，将提供以前无法获得的信息的组织和动态的质膜，仿生结构，和捕光蛋白。 脂质双层和捕光蛋白内的能量耗散还没有被很好地理解，但被认为介导了这两种不同类型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双层成分的浓度和身份而变化。 了解脂筏组织的分子结构基础，需要的粘弹性和分子间相互作用的脂质双层成分可以测量。 拟议的仪器将允许测量的分子运动和生物分子系统中的热能流。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组分如何相互作用，以产生负责能量转导、跨膜转运和分子识别的功能组件。 该仪器将表征脂质和脂质蛋白质的相互作用，控制脂质双层组件的流动性和组件之间的热能流动，作为化学反应和分子运动的驱动力。探针检测方案，以检查振动能量转移和快速分子尺度运动的双层膜和捕光蛋白质。 这样的测量以前是不可能的。 该检测系统是相敏和散粒噪声限制的，以测量107分之一的部分的透射变化。 由于膜中短寿命复合物的形成和衰减的反应动力学是由振动激活的障碍穿越过程控制的，因此用所提出的仪器获得的信息对于理解与空间异质结构（包括脂筏和蛋白质）相关的动力学是至关重要的。创建广泛使用的仪器，推进脂质双层性质和动态测量的最新技术水平，将对密歇根州立大学和区域科学界以及全球科学界产生重大影响。 PI和co-PI与其他MSU部门的教师合作（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），附近机构的教师（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（英国）、新加坡国立大学和陕西师范大学（中国））。 他们还与联邦研究机构合作，如位于伊利诺伊州尚潘的美国陆军工程师研究和发展中心。扩大科学界代表性不足群体的参与至关重要。 密歇根州立大学有多个项目，以连接在高中代表性不足的群体（MSU高中荣誉科学/数学/工程课程（HSHSP），ACS项目种子），本科（全国黑人化学家和化学工程师组织（NOBCChE），DREW/TAC方案），研究生（NOBCChE，MSU非洲裔美国人，拉丁美洲人（a）/奇卡诺人（a），亚洲/太平洋美国人和美洲原住民（ALANA）计划）和研究生水平（MSU赞助的少数民族博士后奖学金）。 PI和co-PI在几个层面上与这些项目合作，并继续努力为所有群体的学生提供实践研究机会和指导。

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.