Collaborative Research: Control of Information Processing and Learning in Neuronal Networks through Light-mediated Programming of Genomic Networks

合作研究:通过基因组网络的光介导编程控制神经网络的信息处理和学习

基本信息

  • 批准号:
    2039190
  • 负责人:
  • 金额:
    $ 36.63万
  • 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:
    2021-02-15 至 2025-01-31
  • 项目状态:
    未结题

项目摘要

Communication and networking play a key role in the development and functioning of living organisms. The physical DNA interactions within the genome, or network of genes, determine gene activities and thereby the development and function of cells, similarly as the software determines the operation of the hardware in a computer. Therefore, being able to program genomic interactions and thereby the development of communicating neuronal networks is at the basis of transformative applications. In this direction, optogenomics, or the control of the genome function through light, is proposed. Optogenomics offers an unprecedented means to control organ and specifically brain development and functions, or even new corrective treatments of cancer and other diseases. Such control will be enabled through development of novel directional light emitting nano-devices. The goal of this inter-disciplinary project is to study information processing and learning (and, thus, ultimately memory) in neuronal networks orchestrated by the light manipulation of the genome. For this, new photonic and electronic tools will be developed to program the genome in neurons and to study both the resulting changes in the structure and activity in networks of living neurons. This project will provide inter-disciplinary training opportunities for graduate and undergraduate students, who will become versed in both nanophotonics and nanoelectronics as well as neuronal cell studies.Beyond optogenetic platforms, which are aimed at the use of light to control cell-cell interactions, optogenomic systems allow the control of DNA interactions in the genome and, thus, the programming of the cell development and function. In this project, new optogenomic tools will be developed to control the development and information processing and learning in neuronal networks. In the proposed system, neural stem cells will be transfected with optimized optogenomic constructs that combine light-activated algae proteins and mammalian genome regulators. As the input to the system, the constructs will be activated globally across the cell culture through LED-based homogeneous illumination. The light-induced changes in the genome 3D structure and function will be analyzed using Chromatin Conformation Capture HiC/HiChIP, Atomic Force Microscopy, and RNAseq with the NextGene global genome sequencing. The output of the system will be the opto-electrophysiological analysis of signal processing in optogenomically constructed neuronal networks, with innovative transparent flexile beamforming nanophotonic devices combined with flexible high-density microelectrode arrays, using metrics like Spike-Timing-Dependent Plasticity, Hebbian learning and network science. An integrated Genome-Neuronal Function Model will be developed for the first time by correlating genomic topological networks to the functional gene networks and ultimately to the properties of the resultant neuronal network as they form in 3D model of the human brain – cerebral organoids.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.
交流和网络在生物体的发育和功能中起着关键作用。基因组或基因网络内的物理DNA相互作用决定了基因活动,从而决定了细胞的发育和功能,类似于计算机中软件决定硬件的操作。因此,能够编程基因组相互作用,从而发展通信神经网络是变革性应用的基础。在这个方向上,光基因组学,或通过光控制基因组功能,被提出。光基因组学提供了一种前所未有的手段来控制器官,特别是大脑的发育和功能,甚至是癌症和其他疾病的新矫正治疗。这种控制将通过新型定向发光纳米器件的发展而实现。这个跨学科项目的目标是研究信息处理和学习(以及最终的记忆)在由基因组的光操纵精心安排的神经网络中。为此,新的光子和电子工具将被开发出来,用于对神经元基因组进行编程,并研究活体神经元网络中结构和活动的变化。该项目将为研究生和本科生提供跨学科的培训机会,使他们精通纳米光子学和纳米电子学以及神经细胞研究。除了旨在利用光来控制细胞间相互作用的光遗传学平台之外,光基因组系统还允许控制基因组中的DNA相互作用,从而控制细胞发育和功能的编程。在这个项目中,将开发新的光基因组工具来控制神经元网络的发展和信息处理和学习。在拟议的系统中,神经干细胞将被优化的光基因组构建物转染,该构建物结合了光激活藻类蛋白和哺乳动物基因组调节因子。作为系统的输入,结构体将通过基于led的均匀照明在整个细胞培养中被全局激活。利用Chromatin构象捕获HiC/HiChIP、原子力显微镜和RNAseq与NextGene全球基因组测序技术分析基因组三维结构和功能的光诱导变化。该系统的输出将是光基因组构建的神经元网络信号处理的光电生理分析,采用创新的透明柔性波束形成纳米光子器件与柔性高密度微电极阵列相结合,使用峰值时间依赖可塑性,Hebbian学习和网络科学等指标。一个集成的基因组-神经元功能模型将首次通过将基因组拓扑网络与功能基因网络相关联,并最终与合成的神经元网络的特性相关联,因为它们形成了人类大脑-脑类器官的3D模型。该奖项反映了美国国家科学基金会的法定使命,并通过使用基金会的知识价值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

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Brain Organoids – expanding on understanding human brain development, schizophrenia and 'Phase Zero' therapies
脑类器官 — 加深对人类大脑发育、精神分裂症和“零阶段”疗法的理解
Joint Nanoscale Communication and Sensing Enabled by Plasmonic Nano-antennas
等离子纳米天线实现联合纳米级通信和传感
Beamforming optical antenna arrays for nano-bio sensing and actuation applications
  • DOI:
    10.1016/j.nancom.2021.100363
  • 发表时间:
    2021-09
  • 期刊:
  • 影响因子:
    0
  • 作者:
    A. Sangwan;J. Jornet
  • 通讯作者:
    A. Sangwan;J. Jornet
Systems genome, Gene Activity Networks, and Recurrent Activity Motifs in control of genome homeostasis; a role of nuclear FGFR1
控制基因组稳态的系统基因组、基因活动网络和循环活动基序;
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Michal Stachowiak其他文献

Michal Stachowiak的其他文献

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{{ truncateString('Michal Stachowiak', 18)}}的其他基金

Novel Nuclear Signaling Mechanisms in Control of FGF-2 Expression in Astrocytes
控制星形胶质细胞中 FGF-2 表达的新型核信号机制
  • 批准号:
    9896349
  • 财政年份:
    1998
  • 资助金额:
    $ 36.63万
  • 项目类别:
    Standard Grant
Novel Nuclear Signaling Mechanisms in Control of FGF-2 Expression in Astrocytes
控制星形胶质细胞中 FGF-2 表达的新型核信号机制
  • 批准号:
    9728923
  • 财政年份:
    1998
  • 资助金额:
    $ 36.63万
  • 项目类别:
    Standard Grant
Novel Nuclear Signaling Mechanisms in Control of FGF-2 Expression in Astrocytes
控制星形胶质细胞中 FGF-2 表达的新型核信号机制
  • 批准号:
    9896371
  • 财政年份:
    1998
  • 资助金额:
    $ 36.63万
  • 项目类别:
    Standard Grant
Regulation of Basic Fibroblast Growth Factor Gene Expressionin Reactive and Neoplastic Astrocytes
反应性星形胶质细胞和肿瘤性星形胶质细胞中碱性成纤维细胞生长因子基因表达的调节
  • 批准号:
    9411226
  • 财政年份:
    1994
  • 资助金额:
    $ 36.63万
  • 项目类别:
    Continuing Grant
Nuclear Mechanisms of the Regulation of Tyrosine HydroxylaseGene in Adrenal Medullary Cells
肾上腺髓质细胞酪氨酸羟化酶基因调控的核机制
  • 批准号:
    9110000
  • 财政年份:
    1991
  • 资助金额:
    $ 36.63万
  • 项目类别:
    Standard Grant

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