CAREER: Experimental & Computational Studies of Ancient Sm-based RNA Assemblies

职业:实验

基本信息

  • 批准号:
    1350957
  • 负责人:
  • 金额:
    $ 73.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-02-01 至 2021-09-30
  • 项目状态:
    已结题

项目摘要

Intellectual Merit: The biological information that defines an organism is stored in its genetic material (DNA), which must be converted into myriad proteins to assemble a live, functioning cell. Many molecular steps are involved in going from DNA to protein, with the biomolecule RNA playing a central role. Indeed, RNA is now thought to be the ancestral molecule at the dawn of life, as it can both store information (like DNA) and act as chemical catalyst (like protein enzymes). A remarkable, evolutionarily conserved family of Sm proteins plays key roles in RNA processing, in organisms ranging from humans to ancient single-celled organisms from the Archaeal branch of life. Sm-mediated pathways vary in scope from mRNA splicing in eukaryotes to RNA-regulated inter-cellular communication networks in bacteria. In each of these pathways at least one key step is mediated by a molecular assembly built upon Sm proteins. Given the ubiquity of the Sm family in contemporary RNA biology, ancient Sm proteins may have played a role in the pivotal transition from an ancestral RNA World to the ribonucleoprotein (RNP) world of modern life. This NSF project focuses on Sm systems from deep-branching archaeal and bacterial species. Leveraging both experiment (biochemistry, proteomics, crystallography) and computation (bioinformatics, simulations), the project will explore what ancient Sm-based RNP complexes look like (structure), their assembly pathways and dynamical behavior (function), and the interrelationships amongst the many Sm systems and their RNA partners (evolution). The work will help discover how the Sm family evolved into a pervasive scaffold for the construction of RNA-based molecular machines. The project's long-term objective - to decipher the biochemical roles of Sm proteins in the early evolution of RNA-associated molecular machines - also will illuminate, in molecular detail, the potential roles of the ancient Sm family in facilitating the transition from a primordial RNA world to our modern RNP world.Broader Impacts: Beyond its scientific impact, this project will educate and train over a dozen under-graduate and graduate students in primary research. Because the project overlaps several disciplines, including biology (RNA, evolution), chemistry (crystallography, molecular simulations) and computer science (bioinformatics), students will learn the biological sciences in a truly integrated and interdisciplinary manner: The driving questions are biological, while the tools and approaches are physical/quantitative. This same multidisciplinary approach, uniting biology and computation, is the basis for the project's central educational plan, dubbed UVaCompBio. The basic model of the UVaCompBio project is that undergraduates from the biosciences and the quantitative sciences (physics, chemistry, CS, etc.) will be paired into teams that work together on active learning exercises and mini-projects over the course of an academic term, and in several areas of computational biology (physics- and informatics-based). This effort will (i) prepare students from the biosciences for quantitative biology, and (ii) give undergraduates from the quantitative sciences a working appreciation of the fascinating nature of complex biological systems. That two-fold goal will, in turn, achieve the ultimate goal of empowering students to be fearless learners who can work at the interfaces between seemingly unrelated scientific disciplines. Thus, over the course of the project period this educational initiative will train scores of undergraduate students and, with an emphasis on quantitative biology and a minority outreach component, will simultaneously and directly address these two major goals of modern science education.
智力价值:定义一个生物体的生物信息储存在它的遗传物质(DNA)中,DNA必须被转化成无数的蛋白质来组装一个活的、有功能的细胞。从DNA到蛋白质涉及许多分子步骤,生物分子RNA起着核心作用。事实上,RNA现在被认为是生命诞生之初的祖先分子,因为它既能存储信息(像DNA),又能作为化学催化剂(像蛋白质酶)。一个显著的,进化保守的Sm蛋白家族在RNA加工中起着关键作用,从人类到古生菌分支的古老单细胞生物。sm介导的途径范围多样,从真核生物的mRNA剪接到细菌中rna调节的细胞间通信网络。在这些途径中,至少有一个关键步骤是由建立在Sm蛋白上的分子组装介导的。鉴于Sm家族在当代RNA生物学中的普遍存在,古代Sm蛋白可能在从祖先RNA世界到现代生活的核糖核蛋白(RNP)世界的关键转变中发挥了作用。这个NSF项目的重点是来自深分支古细菌和细菌物种的Sm系统。利用实验(生物化学,蛋白质组学,晶体学)和计算(生物信息学,模拟),该项目将探索古代基于Sm的RNP复合物的外观(结构),它们的组装途径和动态行为(功能),以及许多Sm系统及其RNA伙伴之间的相互关系(进化)。这项工作将有助于发现Sm家族如何进化成一个无处不在的支架,用于构建基于rna的分子机器。该项目的长期目标——破译Sm蛋白在RNA相关分子机器早期进化中的生化作用——也将在分子细节上阐明古代Sm家族在促进从原始RNA世界向现代RNP世界过渡中的潜在作用。更广泛的影响:除了其科学影响外,该项目将教育和培训十几名本科生和研究生进行初级研究。由于该项目涉及多个学科,包括生物学(RNA,进化),化学(晶体学,分子模拟)和计算机科学(生物信息学),学生将以真正综合和跨学科的方式学习生物科学:驱动问题是生物学的,而工具和方法是物理/定量的。同样的多学科方法,结合生物学和计算,是该项目的中心教育计划的基础,被称为uvaccompbio。uvaccompbio项目的基本模式是,来自生物科学和定量科学(物理、化学、计算机科学等)的本科生将被配对成团队,在一个学期的课程中,在计算生物学的几个领域(基于物理和信息学)共同进行主动学习练习和小型项目。这一努力将(i)使生物科学专业的学生为定量生物学做好准备,(ii)使定量科学专业的本科生对复杂生物系统的迷人本质有一个有效的认识。这一双重目标将反过来实现最终目标,即使学生成为无畏的学习者,能够在看似无关的科学学科之间的界面上工作。因此,在整个项目期间,这一教育计划将培养大量的本科生,并将同时直接解决现代科学教育的这两个主要目标,其重点是定量生物学和少数民族外联部分。

项目成果

期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Toward a Designable Extracellular Matrix: Molecular Dynamics Simulations of an Engineered Laminin-Mimetic, Elastin-Like Fusion Protein
走向可设计的细胞外基质:工程层粘连蛋白模拟、弹性蛋白样融合蛋白的分子动力学模拟
  • DOI:
    10.1021/acs.biomac.6b00951
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    6.2
  • 作者:
    Tang, James D.;McAnany, Charles E.;Mura, Cameron;Lampe, Kyle J.
  • 通讯作者:
    Lampe, Kyle J.
Structural biology meets data science: does anything change?
  • DOI:
    10.1016/j.sbi.2018.09.003
  • 发表时间:
    2018-10-01
  • 期刊:
  • 影响因子:
    6.8
  • 作者:
    Mura, Cameron;Draizen, Eli J.;Bourne, Philip E.
  • 通讯作者:
    Bourne, Philip E.
Crystal structure and RNA-binding properties of an Hfq homolog from the deep-branching Aquificae: conservation of the lateral RNA-binding mode
深分支 Aquiificae 的 Hfq 同源物的晶体结构和 RNA 结合特性:横向 RNA 结合模式的保守
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Cameron Mura其他文献

Cameron Mura的其他文献

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