Administrative Supplements for Equipment Purchases for NIGMS-Funded Award: Quantifying Physiologic and Pathologic Viscoelastic Phases of Biomolecular Condensates by Correlative Force and Fluorescence

NIGMS 资助的设备采购行政补充:通过相关力和荧光量化生物分子凝聚体的生理和病理粘弹性相

基本信息

项目摘要

SUMMARY In recent years, it has become increasingly clear that the material properties of biomolecular condensates (BMCs), which are formed via liquid-liquid phase separation, play crucial roles in both cellular physiology and pathology. Nevertheless, mechanistic understandings of the molecular determinants and modulators of BMC viscoelastic phases remain incomplete due to the limitations of currently available techniques to probe their dynamics across single-molecule to mesoscale. The goal of this proposal is to address this critical gap by the development of a multi-parametric experimental toolbox that simultaneously reports on condensate structure and dynamics across different length scales, with high sensitivity. Our approach will feature correlative multicolor single-molecule fluorescence microscopy, single-molecule spectroscopy, dual-trap optical tweezers, and microfluidics. Utilizing our novel toolbox, we will decipher the mechanisms of liquid-to-liquid and liquid-to-solid phase transitions of intracellular BMCs, processes that critically contribute to the onset or development of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Commonly used fluorescence microscopy techniques, such as fluorescence recovery after photobleaching (FRAP), offer only probe-specific protein/RNA diffusivity within the RNP granules. In contrast, our proposed correlative force-fluorescence microscopy platform will provide a multiscale view of BMC structure and dynamics by taking advantage of optical tweezer-based rheological and fluid dynamics measurements in conjunction with quantification of protein/RNA dynamics using single-molecule fluorescence. Recent results from the project supported by the parent award clearly established that BMCs are network fluids where the network connectivity and dynamics govern their functional output. These results, in conjunction with our recent discovery that oncofusion transcription factors reprogram gene expression via ectopic phase separation in the nucleus, collectively led us to hypothesize that BMC network structure and dynamics from single-molecule-to-mesoscale precisely orchestrate gene regulation within the nuclear chromatin. Overall, our research program will address three Key Challenges (KCs): (a) we will develop a novel multi-parametric approach based on correlative single- molecule fluorescence microscopy, single-molecule spectroscopy, and dual-trap optical tweezer that simultaneously reports on molecular and mesoscale protein-RNA condensate structure and dynamics in vitro and in live cells (KC 1), (b) we will apply our toolbox to map the transition pathways of physiologic BMCs to pathologic states in c9orf72 repeat expansion disorder (KC 2), and (c) we will identify mechanisms of transcriptional condensate formation, regulation, and function at DNA enhancer sites (KC 3). Our studies will provide new insights into the determinants of functional BMC material states, dynamics, and composition, as well as identify novel pathways of their pathologic alterations.
总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Priya R. Banerjee其他文献

Temperature-controlled microrheology illuminates distinctive roles of chain length and sticker strength on material properties of biomolecular condensates
  • DOI:
    10.1016/j.bpj.2023.11.2182
  • 发表时间:
    2024-02-08
  • 期刊:
  • 影响因子:
  • 作者:
    Anurag Singh;Ibraheem Alshareedah;Sean Yang;Vysakh Ramachandran;Alexander Quinn;Davit A. Potoyan;Priya R. Banerjee
  • 通讯作者:
    Priya R. Banerjee
Role of Interaction Modularity in Governing Phase Behavior, Structure and Dynamics of Ternary Protein-RNA Condensates
  • DOI:
    10.1016/j.bpj.2019.11.2951
  • 发表时间:
    2020-02-07
  • 期刊:
  • 影响因子:
  • 作者:
    Taranpreet Kaur;Priya R. Banerjee
  • 通讯作者:
    Priya R. Banerjee
Sequence-Encoded Interactions Modulate Reentrant Liquid Condensation of Ribonucleoprotein-RNA Mixtures
  • DOI:
    10.1016/j.bpj.2019.11.2129
  • 发表时间:
    2020-02-07
  • 期刊:
  • 影响因子:
  • 作者:
    Ibraheem Alshareedah;Priya R. Banerjee
  • 通讯作者:
    Priya R. Banerjee
Divalent Cations Drive Tunable Phase Separation of Homopolymeric RNA Sequences
  • DOI:
    10.1016/j.bpj.2020.11.478
  • 发表时间:
    2021-02-12
  • 期刊:
  • 影响因子:
  • 作者:
    Paulo Onuchic;Anthony Milin;Ibraheem Alshareedah;Priya R. Banerjee;Ashok Deniz
  • 通讯作者:
    Ashok Deniz
Thermodynamic Studies on the Cataract-Associated Mutant, E107a, of Human Gamma-D Crystallin: Molecular Basis for Cataract Formation
  • DOI:
    10.1016/j.bpj.2009.12.254
  • 发表时间:
    2010-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Priya R. Banerjee;Ajay Pande;George Thurston;Jayanti Pande
  • 通讯作者:
    Jayanti Pande

Priya R. Banerjee的其他文献

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{{ truncateString('Priya R. Banerjee', 18)}}的其他基金

Developing a screening platform to identify inhibitors of pathological self-assembly of Tau
开发筛选平台来鉴定 Tau 病理性自组装抑制剂
  • 批准号:
    10323679
  • 财政年份:
    2021
  • 资助金额:
    $ 24.05万
  • 项目类别:
Deciphering the role of low complexity domains in dual specificity kinase function
解读低复杂性结构域在双特异性激酶功能中的作用
  • 批准号:
    10217666
  • 财政年份:
    2021
  • 资助金额:
    $ 24.05万
  • 项目类别:
Quantifying Physiologic and Pathologic Viscoelastic Phases of Biomolecular Condensates by Correlative Force and Fluorescence Microscopy
通过相关力和荧光显微镜量化生物分子凝聚物的生理和病理粘弹性相
  • 批准号:
    10231209
  • 财政年份:
    2020
  • 资助金额:
    $ 24.05万
  • 项目类别:
Quantifying Physiologic and Pathologic Viscoelastic Phases of Biomolecular Condensates by Correlative Force and Fluorescence Microscopy
通过相关力和荧光显微镜量化生物分子凝聚物的生理和病理粘弹性相
  • 批准号:
    10029306
  • 财政年份:
    2020
  • 资助金额:
    $ 24.05万
  • 项目类别:
Quantifying Physiologic and Pathologic Viscoelastic Phases of Biomolecular Condensates by Correlative Force and Fluorescence Microscopy
通过相关力和荧光显微镜量化生物分子凝聚物的生理和病理粘弹性相
  • 批准号:
    10437758
  • 财政年份:
    2020
  • 资助金额:
    $ 24.05万
  • 项目类别:
Quantifying Physiologic and Pathologic Viscoelastic Phases of Biomolecular Condensates by Correlative Force and Fluorescence Microscopy
通过相关力和荧光显微镜量化生物分子凝聚物的生理和病理粘弹性相
  • 批准号:
    10708765
  • 财政年份:
    2020
  • 资助金额:
    $ 24.05万
  • 项目类别:
Mechanism of liquid phase homeostasis of prion-like RNA binding proteins
朊病毒样RNA结合蛋白的液相稳态机制
  • 批准号:
    9809312
  • 财政年份:
    2019
  • 资助金额:
    $ 24.05万
  • 项目类别:

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