SGER:Developing New Methods Based on Folding and Unfolding Pathways

SGER:开发基于折叠和展开路径的新方法

基本信息

  • 批准号:
    0621216
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-10-01 至 2008-03-31
  • 项目状态:
    已结题

项目摘要

Abstract Proposal Title: SGER Developing New Methods Based on Folding and Unfolding Pathways. Proposal Number: CTS-0621216 Principal Investigator: Anubhav Tripathi, Institution: Brown University Intellectual Merit: High resolution separation methodologies aim to resolve complex mixtures of macromolecules into individual components for subsequent identification of macromolecular expression patterns and, on a broader scale, gain a fundamental understanding of biological system regulation. Common separation strategies are: (1) electrophoresis in which macromolecules are separated based on electrophoretic mobility and isoelectric point, and (2) chromatography in which the macromolecules are separated based on mobility, hydrophobicity and/or affinity. Since these strategies use either fully folded or fully denatured macromolecules, it is extremely difficult to resolve macromolecules with similar mobilities, isoelectric points and/or hydrophobicities. Proteins and RNAs are two examples of macromolecules which adopt different folded-unfolded structures based on the quality of aqueous environment which can disrupt the hydrophobic interactions or alter the net charge on the molecule causing electrostatic repulsion or disruption of some hydrogen bonds. A new research direction in separation and purification science, in which macromolecules such as proteins and RNAs can be targeted to adopt different folding-unfolding pathways under specific buffer conditions, is needed. Under these conditions, two molecules can be separated based on the "enhanced" difference in their mobility or adsorption/desorption characteristics. The investigator has recently demonstrated that two isoforms of lactoglobulin possess conformationally different structures under certain buffer conditions. In this SGER proposal, the PI has requested funding to perform preliminary experiments to demonstrate that under specific buffer conditions, due to differences in conformations, the two isoforms have different mobilities and different adsorption isotherms. Furthermore, differences in mobilities and adsorption behavior can be used to separate the two isoforms using (a) electrophoresis and (b) adsorption on a packed bed of spheres in microchip geometry. The results from this SGER will validate the claim that the changes in protein properties that accompany partial unfolding might be utilized for separation. If successful, the PI anticipates that this SGER proposal will lead to a more detailed CAREER proposal where the intimate details of protein folding and unfolding pathways will be modeled and characterized within a carefully crafted experimental and teaching plan. The broader impact of research is the quantification of macromolecules with similar mobilities that has become important in light of their central role in pathological states of mutations, improper expression or function (e.g. prion and various cancers). In the future, a research program in this area might offer a quality control process to test purity and stability of recombinant human proteins. The program also might offer a screening method for the pharmaceutical industry where binding ability of thousands of ligand molecules can be tested to inhibit the activity of a relevant target enzyme or protein. The fundamental experiments to be performed in this SGER will explore these issues and will provide several host new topics for interdisciplinary research. The educational program couples core skills of thermodynamics, kinetics and transport phenomenon to separation and purification science.
摘要提案标题:SGER开发基于折叠和展开路径的新方法。建议编号:CTS-0621216首席研究员:Anubhav Tripari,研究所:布朗大学学术价值:高分辨率分离方法的目标是将复杂的大分子混合物分解成单独的组分,以便随后识别大分子表达模式,并在更广泛的范围内获得对生物系统调节的基本理解。常见的分离策略有:(1)根据电泳率和等电点来分离大分子的电泳法,以及(2)根据迁移率、疏水性和亲和力来分离大分子的层析法。由于这些策略要么使用完全折叠的大分子,要么使用完全变性的大分子,因此拆分具有相似迁移率、等电点和/或疏水性的大分子是极其困难的。蛋白质和RNA是两种大分子,它们根据水环境的质量采用不同的折叠-展开结构,这些结构可以破坏分子上的疏水相互作用或改变分子上的净电荷,导致静电斥力或某些氢键的破坏。在分离纯化科学中需要一个新的研究方向,即在特定的缓冲条件下,可以针对蛋白质和RNA等大分子采取不同的折叠-去折叠途径。在这些条件下,两个分子可以根据它们的流动性或吸附/解吸特性的“增强”差异而被分离。研究人员最近证明,在某些缓冲条件下,乳球蛋白的两种异构体具有不同的构象结构。在这份SGER提案中,PI已申请资金进行初步实验,以证明在特定的缓冲条件下,由于构象的不同,两种异构体具有不同的迁移率和不同的吸附等温线。此外,迁移率和吸附行为的差异可用于通过(A)电泳和(B)在微芯片几何形状的球体填充床上吸附来分离这两种异构体。这一SGER的结果将证实这样的说法,即伴随着部分展开而来的蛋白质性质的变化可能被用于分离。如果成功,PI预计SGER的这项提案将导致一份更详细的职业提案,其中蛋白质折叠和展开途径的亲密细节将在精心设计的实验和教学计划中建模和表征。研究的更广泛影响是对具有相似迁移率的大分子进行量化,鉴于它们在突变、不适当表达或功能的病理状态中的核心作用(例如,Pron和各种癌症),这一点已经变得重要。未来,这一领域的研究计划可能会提供一种质量控制方法来测试重组人蛋白的纯度和稳定性。该计划还可能为制药行业提供一种筛选方法,可以测试数千个配体分子的结合能力,以抑制相关靶酶或蛋白质的活性。将在这个SGER中进行的基础实验将探索这些问题,并将为跨学科研究提供几个新的主题。该教育项目将热力学、动力学和传输现象的核心技能与分离和纯化科学结合起来。

项目成果

期刊论文数量(0)
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会议论文数量(0)
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Anubhav Tripathi其他文献

Innovative Method for Fully Automated, Enzyme-Free Tissue Dissociation and Preparation for Single-Cell Analysis
  • DOI:
    10.1007/s12195-025-00850-5
  • 发表时间:
    2025-07-03
  • 期刊:
  • 影响因子:
    5.000
  • 作者:
    Sarah Planchak;E. Celeste Welch;Benjamin Phelps;Joshua Phelps;Alejandra Hernandez Moyers;Kathryn Whitehead;John Murphy;Nikos Tapinos;Anubhav Tripathi
  • 通讯作者:
    Anubhav Tripathi
Correlative Analysis and Impact of Intelligent Virtual Assistants on Machine Learning
智能虚拟助理对机器学习的相关分析及影响
Opioid quantification via microsampling techniques to assess opioid use in human laboratory studies
  • DOI:
    10.1038/s41598-025-99130-5
  • 发表时间:
    2025-05-21
  • 期刊:
  • 影响因子:
    3.900
  • 作者:
    Ramisa Fariha;Emma Rothkopf;Carolina L. Haass-Koffler;Anubhav Tripathi
  • 通讯作者:
    Anubhav Tripathi
Bioimpedance Spectroscopy System for Glioblastoma Spheroid Growth and Dissociation Characterization
用于胶质母细胞瘤球体生长和解离表征的生物阻抗光谱系统
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Riley Renee Flores;E. Welch;Anubhav Tripathi
  • 通讯作者:
    Anubhav Tripathi
Diuretic bioactivity optimization of furosemide in rats
  • DOI:
    10.1016/j.ejpb.2011.04.014
  • 发表时间:
    2011-10-01
  • 期刊:
  • 影响因子:
  • 作者:
    Bryan Laulicht;Anubhav Tripathi;Edith Mathiowitz
  • 通讯作者:
    Edith Mathiowitz

Anubhav Tripathi的其他文献

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{{ truncateString('Anubhav Tripathi', 18)}}的其他基金

Collaborative Research: Direct Exploration of New Nanoscale Structures using a Microfluidic Chip Integrated with Cryo-TEM
合作研究:使用与 Cryo-TEM 集成的微流控芯片直接探索新的纳米级结构
  • 批准号:
    0854097
  • 财政年份:
    2009
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Collaborative Research: Understanding UV Protective Mechanisms Using Hybrid Nanoarchitectures
合作研究:利用混合纳米结构了解紫外线防护机制
  • 批准号:
    0756600
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Separation of Macromolecules Based on Conformation Pathways
基于构象途径的大分子分离
  • 批准号:
    0756588
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Collaborative Research: DNA Amplification in a novel integrated microchip platform with temporal thermal control
合作研究:具有时间热控制的新型集成微芯片平台中的 DNA 扩增
  • 批准号:
    0653835
  • 财政年份:
    2007
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
A CONTINUOUS FLOW MICROREACTOR FOR LINEAR RNA AMPLIFICATION
用于线性 RNA 扩增的连续流微反应器
  • 批准号:
    0555874
  • 财政年份:
    2006
  • 资助金额:
    --
  • 项目类别:
    Standard Grant

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