Collaborative Research: MODULUS:Decoding the Rules of Phase Separation in Bacterial Chromatin

合作研究:MODULUS:解码细菌染色质相分离规则

基本信息

  • 批准号:
    2031179
  • 负责人:
  • 金额:
    $ 55.97万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-01-01 至 2024-12-31
  • 项目状态:
    已结题

项目摘要

All life depends on compartmentalization, starting with organisms, to cells, down to organelles within cells. In this interdisciplinary collaboration, the PIs will elucidate the rules underlying cellular compartmentalization in bacteria. While compartmentalization within cells is often facilitated by membranes, bacteria do not typically contain membrane-enclosed organelles. Instead, bacteria must rely on alternate mechanisms such as phase separation for spatial and functional organization and regulation of biochemical activity. This mechanism allows for the formation of distinct phases or domains with different structures, functions, and material properties starting from a homogeneous mixture. Recently, soft-matter theories of phase separation of liquid mixtures have tremendously advanced understanding of the biological organization. However, the bacterial cytoplasm consists of mixtures of complex, structured fluids. Their phase separation and regulation by non-equilibrium processes such as enzymatic activity are not well understood. The PIs will use data-driven mathematical modeling and state-of-the-art experiments to obtain a quantitative understanding of the formation of phase-separated condensates and their impact on the organization of genetic material and protein diffusion in bacteria. The findings will provide insights into how intracellular phase separation drives and determines cellular properties and functions, and connects genotype to phenotype. The PIs will educate and train a new generation of scientists in mathematical modeling and biology, and promote diversity in the STEM workforce. They will co-organize Biophysics workshops to stimulate interactions among scientists and industrial labs and introduce trainees to the local academic and industrial research community.Cells use compartmentalization to create spatial organization, allowing them to carry out biochemical processes and control biomolecular structures within distinct microenvironments. This collaborative project will test the hypothesis that bacteria use intracellular phase separation to achieve compartmentalization, allowing for rapid exchange of molecules with the cytoplasm without the need for internal membranes. Upon stress, bacterial chromosomes are reorganized by the Dps protein into a tightly compacted condensate with liquid crystalline properties. To determine the biophysical mechanisms underlying Dps-DNA condensates, single-molecule fluorescence microscopy will map the phase diagram of the condensate system as a function of physiologically relevant environmental conditions. These experiments will complement active particle and continuum models that will predict the phase-separated morphologies and the degree of liquid crystallinity of the condensate. The viscoelastic and mechanical structure-function properties of the condensate will be measured via active microrheology; polarized light microscopy will identify any large ordered domains within the condensate. Mathematical approaches will determine the structural and orientational order, allowing for the construction of a microscopic model of the phase separation and phase ordering of the condensate. To evaluate the hypothesis that small molecules can diffuse rapidly within Dps:DNA condensates to promote enzymatic activities including transcription, the diffusion of molecules within condensed droplets will be directly measured by total internal reflection fluorescence microscopy. Mathematical examination of the particle trajectories will reveal the accessibility of different DNA regions and quantitatively characterize the motility of different types of biomolecules, advancing the understanding of how structure-function properties of biomolecular condensates regulate cellular activities.This award is being co-funded by the Division of Molecular and Cellular Biosciences (MCB) through the Systems and Synthetic Biology and the Genetic Mechanisms Programs, and the MPS Division of Mathematical Sciences (DMS) through the Mathematical Biology Program.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
所有的生命都依赖于划分,从有机体开始,到细胞,再到细胞内的细胞器。在这一跨学科合作中,PI将阐明细菌细胞区隔的基本规则。虽然细胞内的隔间作用通常是由膜促进的,但细菌通常不包含膜封闭的细胞器。相反,细菌必须依靠其他机制,如相分离来进行空间和功能组织以及生化活动的调节。这种机制允许从均匀的混合物开始形成具有不同结构、功能和材料性质的不同相或区域。最近,液体混合物相分离的软物质理论极大地提高了对生物组织的理解。然而,细菌细胞质是由复杂的、有结构的液体组成的混合物。它们的相分离和非平衡过程的调节,如酶活性,还没有被很好地理解。PI将使用数据驱动的数学建模和最先进的实验,以获得对相分离冷凝物的形成及其对遗传物质的组织和细菌中蛋白质扩散的影响的定量了解。这些发现将为深入了解细胞内相分离如何驱动和决定细胞的属性和功能,以及如何将基因型与表型联系起来提供见解。PIS将在数学建模和生物学方面教育和培训新一代科学家,并促进STEM劳动力的多样性。他们将共同组织生物物理研讨会,以促进科学家和工业实验室之间的互动,并将受训人员介绍给当地的学术和工业研究社区。细胞使用分区来创建空间组织,使它们能够在不同的微环境中进行生化过程和控制生物分子结构。这个合作项目将测试细菌使用细胞内相分离来实现分隔化的假设,允许分子与细胞质快速交换,而不需要内膜。在压力下,细菌的染色体被DPS蛋白重组成紧密致密的具有液晶特性的凝聚体。为了确定DPS-DNA冷凝物的生物物理机制,单分子荧光显微镜将绘制冷凝物体系的相图,作为生理相关环境条件的函数。这些实验将补充活性粒子和连续介质模型,这些模型将预测凝析油的相分离形态和液晶度。凝析油的粘弹性和机械结构-功能特性将通过主动微观流变学进行测量;偏振光显微镜将识别凝析油中的任何大的有序区域。数学方法将确定凝析油的结构和取向顺序,从而建立凝析油相分离和相有序的微观模型。为了评估小分子可以在DPS内快速扩散的假设:DNA缩合物可以促进包括转录在内的酶活性,将通过全内反射荧光显微镜直接测量凝聚液滴中分子的扩散。对粒子轨迹的数学研究将揭示不同DNA区域的可及性,并定量描述不同类型生物分子的运动性,促进对生物分子凝聚体结构-功能特性如何调节细胞活动的理解。该奖项由分子和细胞生物科学部(MCB)通过系统和合成生物学以及遗传机制计划和MPS数学科学部(DMS)通过数学生物学计划共同资助。该奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。

项目成果

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Moumita Das其他文献

A kernel-enriched order-dependent nonparametric spatio-temporal process
核丰富的阶依赖非参数时空过程
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    2.3
  • 作者:
    Moumita Das;S. Bhattacharya
  • 通讯作者:
    S. Bhattacharya
Compressive stress triggers fibroblasts spreading over cancer cells to generate carcinoma in situ organization
压缩应力触发成纤维细胞在癌细胞上扩散以产生原位癌组织
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    5.9
  • 作者:
    Fabien Bertillot;Laetitia Andrique;Carlos Ureña Martin;Olivier Zajac;L. de Plater;Michael M Norton;Aurélien Richard;K. Alessandri;Basile G. Gurchenkov;Florian Fage;A. Asnacios;Christophe Lamaze;Moumita Das;J. Maître;Pierre Nassoy;Danijela Matic Vignjevic
  • 通讯作者:
    Danijela Matic Vignjevic
Probing quantum correlations in non-degenerate hyper-Raman process
  • DOI:
    10.1140/epjp/s13360-025-06161-y
  • 发表时间:
    2025-03-18
  • 期刊:
  • 影响因子:
    2.900
  • 作者:
    Moumita Das;Biswajit Sen;Ankur Sensharma;Kishore Thapliyal;Anirban Pathak
  • 通讯作者:
    Anirban Pathak
Enhancing Speculative Execution With Selective Approximate Computing
通过选择性近似计算增强推测执行
Contextual Prediction Errors Reorganize Episodic Memories in Time
上下文预测错误及时重组情景记忆
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Fahd Yazin;Moumita Das;A. Banerjee;Dipanjan Roy
  • 通讯作者:
    Dipanjan Roy

Moumita Das的其他文献

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{{ truncateString('Moumita Das', 18)}}的其他基金

Collaborative Research: Biomechanical mechanisms conferring wound resilience in single-celled organisms
合作研究:赋予单细胞生物伤口复原力的生物力学机制
  • 批准号:
    2317443
  • 财政年份:
    2023
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF Workshop on Models for Uncovering Rules and Unexpected Phenomena in Biological Systems (MODULUS)
合作研究:NSF 揭示生物系统规则和意外现象模型研讨会 (MODULUS)
  • 批准号:
    2232740
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: DMREF: Living biotic-abiotic materials with temporally programmable actuation
合作研究:DMREF:具有临时可编程驱动的生物-非生物活性材料
  • 批准号:
    2118449
  • 财政年份:
    2021
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: Bottom-up Construction of a Synthetic Neuron and Programmable Neuronal Network
合作研究:合成神经元和可编程神经元网络的自下而上构建
  • 批准号:
    1935277
  • 财政年份:
    2019
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: Decoding and encoding mechanistic relations between structure and function in crack resistance of articular cartilage and cartilage inspired biomaterials.
合作研究:解码和编码关节软骨和软骨启发生物材料的抗裂结构和功能之间的机械关系。
  • 批准号:
    1808026
  • 财政年份:
    2018
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Continuing Grant
Biorheology of the vitreous gel
玻璃体凝胶的生物流变学
  • 批准号:
    1604712
  • 财政年份:
    2016
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant

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Research on Quantum Field Theory without a Lagrangian Description
  • 批准号:
    24ZR1403900
  • 批准年份:
    2024
  • 资助金额:
    0.0 万元
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Cell Research
  • 批准号:
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Cell Research
  • 批准号:
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  • 批准年份:
    2010
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Cell Research (细胞研究)
  • 批准号:
    30824808
  • 批准年份:
    2008
  • 资助金额:
    24.0 万元
  • 项目类别:
    专项基金项目
Research on the Rapid Growth Mechanism of KDP Crystal
  • 批准号:
    10774081
  • 批准年份:
    2007
  • 资助金额:
    45.0 万元
  • 项目类别:
    面上项目

相似海外基金

Collaborative Research: MODULUS: Protein droplets drive membrane bending and cytoskeletal organization
合作研究:MODULUS:蛋白质液滴驱动膜弯曲和细胞骨架组织
  • 批准号:
    2327243
  • 财政年份:
    2023
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Continuing Grant
Collaborative Research: MODULUS: Protein droplets drive membrane bending and cytoskeletal organization
合作研究:MODULUS:蛋白质液滴驱动膜弯曲和细胞骨架组织
  • 批准号:
    2327244
  • 财政年份:
    2023
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF Workshop on Models for Uncovering Rules and Unexpected Phenomena in Biological Systems (MODULUS)
合作研究:NSF 揭示生物系统规则和意外现象模型研讨会 (MODULUS)
  • 批准号:
    2232740
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF Workshop on Models for Uncovering Rules and Unexpected Phenomena in Biological Systems (MODULUS)
合作研究:NSF 揭示生物系统规则和意外现象模型研讨会 (MODULUS)
  • 批准号:
    2232741
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: MODULUS: Nuclear envelope shape change coordination with chromosome segregation in mitosis in fission yeast
合作研究:MODULUS:核膜形状变化与裂殖酵母有丝分裂中染色体分离的协调
  • 批准号:
    2133243
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: MODULUS: Copy Number Alterations and Xenobiotic adaptation
合作研究:MODULUS:拷贝数改变和异生素适应
  • 批准号:
    2141650
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF Workshop on Models for Uncovering Rules and Unexpected Phenomena in Biological Systems (MODULUS)
合作研究:NSF 揭示生物系统规则和意外现象模型研讨会 (MODULUS)
  • 批准号:
    2232739
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: NSF Workshop on Models for Uncovering Rules and Unexpected Phenomena in Biological Systems (MODULUS)
合作研究:NSF 揭示生物系统规则和意外现象模型研讨会 (MODULUS)
  • 批准号:
    2232742
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: MODULUS: Stochastic reaction-diffusion equations on metric graphs and spatially-resolved dynamics of virus infection spread
合作研究:MODULUS:度量图上的随机反应扩散方程和病毒感染传播的空间分辨动力学
  • 批准号:
    2151959
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
    Standard Grant
Collaborative Research: MODULUS: Nuclear envelope shape change coordination with chromosome segregation in mitosis in fission yeast
合作研究:MODULUS:核膜形状变化与裂殖酵母有丝分裂中染色体分离的协调
  • 批准号:
    2133276
  • 财政年份:
    2022
  • 资助金额:
    $ 55.97万
  • 项目类别:
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