CAREER: Studying Weak Interactions in Biological Systems, Forming Strong Interactions Between Students

职业:研究生物系统中的弱相互作用,在学生之间形成强相互作用

基本信息

  • 批准号:
    0845676
  • 负责人:
  • 金额:
    $ 54.32万
  • 依托单位:
  • 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:
    2009-04-01 至 2014-03-31
  • 项目状态:
    已结题

项目摘要

For the delivery of signaling molecules in a cell to occur, the membranes of the vesicle in which signaling molecules are packaged must fuse with another membrane. As timing is vital in cellular processes, this delivery of signaling molecules must be poised to trigger only when the appropriate signal or combinations of cellular signals transpire. Although this is a critical cellular event, how this regulated delivery occurs is not well understood. Membranes are comprised of a great diversity of lipids whose individual lipid-lipid interactions are weak and interactions within the membrane dictated by the lipids' chemical structure and its local milieu. These factors govern the resultant lipid's activity (effective concentration) and hence, how the membrane is targeted for binding to or partitioning into by proteins. Within this model, it is hypothesized that intrinsically weak interactions between lipids are critical for the system to reversibly and rapidly organize the protein clusters that modulate signaling. This offers a more nuanced regulation of biological events beyond a system dominated by a few, very strong interactions. These small interaction energies offer flexibility in how combinations of lipids, in response to proteins binding, form signaling platforms. This concept is hypothesized to be the basis for how key proteins involved in regulated delivery target distinct membranes. The objective of this project is to test the hypothesis that these key proteins are modulated not by a few strong interactions but by a necessary ensemble of weak interactions at the membrane. Testing will involve quantitative analysis and rigorous use of binding theory and thermodynamic (linkage) relationships by undergraduates from diverse scientific disciplines. New techniques, both conceptual and experimental, will also result from this project that will be applicable to many questions of biological relevance. The classic use of linkage relationships is an example of problem-based learning where biological processes are simply represented mathematically and interpreted. Each experiment becomes a case study and the derivation of equations is no longer restricted to assigned homework or to be used after years of graduate training. The goal is to demonstrate that undergraduates and young graduate students can propose, use, explore, and test these concepts. Broader Impacts The Broader Impacts of this project include the development of methodologies that will enhance the persistence, retention, and future success of women in scientific careers. By improving the educational environment for women, the educational environment not only for underrepresented groups but for all students will be improved. The methodologies will have two components, Informal and Formal Education. The Informal structure for this change is a scientific council, named Interactions. This council will integrate all issues that are faced by future science, mathematics and engineering (SME) professionals. Potential topics will include: social dynamics (e.g. bias), the importance of building a community in addition to a resume (or CV), the need to apply for research scholarships, academic scholarships and awards, and how these experiences can shape your future. Interactions will provide in-house educational meetings and host motivating role models such as distinguished female scientists, alumni, and scientists from the region who have gone on to illustrious careers. Interactions will also foster peer group learning. The existence of peer group learning has been identified by SME students as having the most immediate and most effective contribution to increasing persistence of students within SME majors. The Formal component is a Physical Biochemistry capstone course with laboratory capturing the convergence of topics across the major and explicitly uniting concepts through application. The linkage of biochemistry with other disciplines will be through quantitative literacy where the grammar is Physical Chemistry. A course focused upon practical outcomes will emphasize female specific advantages in learning as it is argued that many other learning strategies are inherently favorable to male learning patterns. Gender differences in learning strategies will be equalized through multiple approaches to problem solving, and the commonalities between seemingly diverse topics will be emphasized.
为了在细胞中传递信号分子,包裹信号分子的囊泡的膜必须与另一膜融合。由于时间在细胞过程中至关重要,这种信号分子的传递必须准备好只有在适当的信号或细胞信号的组合发出时才会触发。虽然这是一个关键的细胞事件,但这种受调控的传递是如何发生的还不是很清楚。膜由多种不同的脂类组成,它们各自的脂类相互作用很弱,膜内的相互作用由脂类的化学结构和局部环境决定。这些因素决定了生成的脂类的活性(有效浓度),从而决定了膜如何被蛋白质结合或分配到膜上。在这个模型中,假设脂类之间内在的弱相互作用对于系统可逆地快速组织调节信号的蛋白质簇至关重要。这为生物事件提供了一种更微妙的监管,而不是由几个非常强的相互作用主导的系统。这些小的相互作用能为脂类组合如何响应蛋白质结合形成信号平台提供了灵活性。这一概念被认为是参与调控递送的关键蛋白如何针对不同的膜的基础。这个项目的目标是检验这样一个假设,即这些关键蛋白质不是受几个强相互作用调节,而是受细胞膜上必要的一系列弱相互作用调节。测试将涉及来自不同科学学科的本科生对束缚理论和热力学(联系)关系的定量分析和严格使用。这个项目还将产生新的技术,无论是概念上的还是实验上的,这将适用于许多与生物学相关的问题。链接关系的经典应用是基于问题的学习的一个例子,在这种学习中,生物过程简单地用数学表示和解释。每一个实验都成为一个案例研究,公式的推导不再局限于指定的家庭作业,也不再局限于经过多年的研究生培训后使用。其目的是展示本科生和年轻的研究生可以提出、使用、探索和测试这些概念。更广泛的影响这一项目的更广泛的影响包括制定方法,以加强妇女在科学事业中的持久力、保留力和未来的成功。通过改善妇女的教育环境,不仅将改善代表人数不足的群体的教育环境,而且将改善所有学生的教育环境。这些方法将包括两个部分,非正规教育和正规教育。这一变化的非正式结构是一个名为交互作用的科学理事会。该委员会将整合未来科学、数学和工程(SME)专业人员面临的所有问题。潜在的话题将包括:社会动态(例如偏见),除了简历(或简历)之外建立一个社区的重要性,申请研究奖学金、学术奖学金和奖项的必要性,以及这些经历如何塑造你的未来。互动将提供内部教育会议,并主持激励榜样,如杰出的女科学家、校友和来自该地区的科学家,她们已经取得了辉煌的职业生涯。互动还将促进同龄人小组学习。同行小组学习的存在被中小企业学生认定为对提高中小企业专业学生的坚持性具有最直接和最有效的贡献。正式的组成部分是一门物理生物化学的顶峰课程,有实验室捕捉到各专业主题的汇聚,并通过应用明确地将概念统一起来。生物化学与其他学科的联系将通过量化素养来实现,其中语法是物理化学。一门注重实践成果的课程将强调女性在学习中的独特优势,因为有人认为,许多其他学习策略天生就有利于男性的学习模式。学习策略上的性别差异将通过多种解决问题的方法来平衡,并将强调看似不同主题之间的共性。

项目成果

期刊论文数量(0)
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Anne Hinderliter其他文献

Exploring the Structural Properties of Synaptotagmin's Intrinsically Disordered Region
  • DOI:
    10.1016/j.bpj.2018.11.1113
  • 发表时间:
    2019-02-15
  • 期刊:
  • 影响因子:
  • 作者:
    Michael E. Fealey;Anne Hinderliter;David D. Thomas
  • 通讯作者:
    David D. Thomas
Diminished Cooperativity: Comparing Linker Lengths in Synaptotagmin I C2A Domain
  • DOI:
    10.1016/j.bpj.2009.12.1326
  • 发表时间:
    2010-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jesse R. Murphy;Kristofer J. Knutson;Jacob W. Gauer;R. Bryan Sutton;Anne Hinderliter
  • 通讯作者:
    Anne Hinderliter
Structure and Mutation Analysis of the C2A Domain of Human Dysferlin Provides a Thermodynamic Basis for Limb-Girdle Muscular Dystrophy
  • DOI:
    10.1016/j.bpj.2010.12.2432
  • 发表时间:
    2011-02-02
  • 期刊:
  • 影响因子:
  • 作者:
    Kerry L. Fuson;Nathan Quisenberry;Thomas Walz;Danijela Dukovski;Anne Hinderliter;R. Bryan Sutton
  • 通讯作者:
    R. Bryan Sutton
Maintenance Cognition Stimulus Therapy: A Survey Paper
维持认知刺激疗法:调查论文
Conformational Flexibility in Membrane Binding Proteins: Synaptotagmin I C2A
  • DOI:
    10.1016/j.bpj.2009.12.1479
  • 发表时间:
    2010-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Jacob W. Gauer;Jesse Murphy;Kristofer Knutson;R. Bryan Sutton;Greg Gillispie;Anne Hinderliter
  • 通讯作者:
    Anne Hinderliter

Anne Hinderliter的其他文献

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{{ truncateString('Anne Hinderliter', 18)}}的其他基金

Entropic Springs in Tandem Repeat Proteins
串联重复蛋白中的熵泉
  • 批准号:
    1616854
  • 财政年份:
    2016
  • 资助金额:
    $ 54.32万
  • 项目类别:
    Standard Grant

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