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

• 批准号: 2039189
• 负责人: Josep Jornet
• 金额: $ 23.32万
• 依托单位: Northeastern University
• 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
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2039189&HistoricalAwards=false
• 关键词: Collaborative; Research; Control; Information; Processing

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.

通信和网络在生物体的发育和功能中发挥着关键作用，基因组或基因网络内的物理 DNA 相互作用决定基因活动，从而决定细胞的发育和功能，就像软件决定细胞的运行一样。因此，能够对基因组相互作用进行编程，从而发展通信神经网络是光基因组学或通过光控制基因组功能的基础。一种前所未有的控制器官的手段，特别是大脑的发育和功能，甚至癌症和其他疾病的新的纠正治疗将通过开发新型定向发光纳米设备来实现。这个跨学科项目的目标是研究信息处理和学习。为此，将开发新的光子和电子工具来对神经元中的基因组进行编程，并研究生命网络中结构和活动的变化。该项目将提供跨学科的培训机会。面向研究生和本科生，他们将精通纳米光子学和纳米电子学以及神经元细胞研究。除了旨在利用光控制细胞间相互作用的光遗传学平台之外，光基因组系统还可以控制 DNA 相互作用在该项目中，将开发新的光基因组工具来控制神经网络的发育、信息处理和学习，在所提出的系统中，神经干细胞将被转染。优化的光基因组结构结合了光激活藻类蛋白和哺乳动物基因组调节剂，作为系统的输入，该结构将通过基于 LED 的均匀照明在整个细胞培养物中被全局激活，从而引起基因组 3D 结构的变化。系统的输出将是使用染色质构象捕获 HiC/HiChIP、原子力显微镜和 RNAseq 以及 NextGene 全球基因组测序来分析和功能。使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，使用尖峰时序依赖性可塑性、赫布学习和网络科学等指标，对光基因组构建的神经网络中的信号处理进行光电生理分析。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，并最终与所形成的神经网络的属性相关联来开发。人脑 3D 模型 - 脑类器官。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力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

Global Genome Conformational Programming during Neuronal Development Is Associated with CTCF and Nuclear FGFR1—The Genome Archipelago Model

神经元发育过程中的全球基因组构象编程与 CTCF 和核 FGFR1 相关——基因组群岛模型

• DOI: 10.3390/ijms22010347
• 发表时间: 2021-01
• 期刊: International Journal of Molecular Sciences
• 影响因子: 5.6
• 作者: Decker, Brandon;Liput, Michal;Abdellatif, Hussam;Yergeau, Donald;Bae, Yongho;Jornet, Josep M.;Stachowiak, Ewa K.;Stachowiak, Michal K.
• 通讯作者: Stachowiak, Michal K.

Plasmonic Nano-systems for Joint Communication and Bio-sensing in the Internet of Nano-Bio Things

用于纳米生物物联网联合通信和生物传感的等离子体纳米系统

• 发表时间: 2022-01
• 期刊: IEEE journal on selected areas in communications
• 影响因子: 16.4
• 作者: Sangwan, Amit;Jornet, Josep Miquel
• 通讯作者: Jornet, Josep Miquel

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

• DOI: 10.1145/3477206.3477447
• 发表时间: 2021-09
• 期刊: Proceedings of the Eight Annual ACM International Conference on Nanoscale Computing and Communication
• 作者: Sangwan, Amit;Jornet, Josep Miquel
• 通讯作者: Jornet, Josep Miquel

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

• 发表时间: 2021-01
• 期刊: 13th INAR conference and 7th International Conference
• 作者: Stachowiak; Michal K.
• 通讯作者: Michal K.

Multi-physics Analysis of Electromagnetic Wave Propagation and Photothermal Heating in Human Tissues at Terahertz and Optical Frequencies

太赫兹和光频率下人体组织中电磁波传播和光热加热的多物理场分析

• DOI: 10.1109/dcoss54816.2022.00064
• 发表时间: 2022-05
• 期刊: 2022 18th International Conference on Distributed Computing in Sensor Systems (DCOSS
• 作者: Reddy, Innem V.;Jornet, Josep M.
• 通讯作者: Jornet, Josep M.