New Methodologies for Connectomics

连接组学的新方法

基本信息

批准号：
10542794
负责人：
Xiaotang Lu
金额：
$ 13.32万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10542794
关键词：
Aging Animal Behavior Animals Axon BRAIN initiative Behavior Disorders Binding Biochemistry Brain Brain imaging Brain region Callithrix Career Choice Cells Cellular biology Characteristics Chemistry Chimeric Proteins Collaborations Color Core Facility Data Set Dendrites Development Dimensions Disease Educational workshop Effectiveness Electron Microscopy Electrons Ensure Environment Fluorescence Microscopy Foundations Funding Future Goals Grant Heavy Metals Human Image Immunization Immunohistochemistry Investigation Knowledge acquisition Label Lanthanoid Series Elements Learning Libraries Light Maps Membrane Mentors Mentorship Metals Methodology Methods Microscopic Microscopy Molecular Molecular Biology Molecular and Cellular Biology Monoclonal Antibodies Multimodal Imaging Mus Nervous System Neurobiology Neurons Neurosciences Osmium Permeability Phase Positioning Attribute Preparation Probability Process Property Proteins Protocols documentation Reagent Research Research Design Resolution Roentgen Rays Running Sampling Series Stains Structure Students Synapses Technology Time Tissue imaging Tissues Tracer Training Tupaiidae Viral Visualization Work Writing X ray microscopy X-Ray Medical Imaging brain research brain tissue brain volume career cell type comparative connectome connectome data graduate student imaging modality interest light microscopy light scattering machine learning algorithm materials science meetings member microCT microscopic imaging miniaturize multimodality multiplexed imaging nanobodies nanometer resolution neural neural circuit neural network recruit screening skills tool

项目摘要

PROJECT ABSTRACT The nervous systems of animals are comprised of neurons connected by a large number of synapses. The resulting neural networks underlie animal behavior and contribute to the storage of learned information in many species. In humans, the miswiring of neural networks likely results in disorders of behavior, learning, and thought. For all these reasons, understanding the development, organization, and disruptions in neural circuits is vital. The goal of connectomics is to produce and study the maps of neuronal connections within nervous systems. Connectomic research requires automated image acquisition of brain tissue images that cover large volumes at high magnification to resolve synapses and methods to generate wiring diagrams from these images. But the connectivity map itself is nevertheless not sufficient to explain the brain functions. Additional information, such as the molecular identity of neurons, needs to be extracted from the same nervous system. The primary goal of this proposal is to develop the heavy metal staining of whole mouse brains and other large brain samples for volumetric electron microscopic mapping of a full connectome (Aim1), generate a library of miniaturized protein binders for correlated light and electron microscopic imaging to bridge connectomics with neuronal cell type studies (Aim2), and expand the use of X-ray microscopy in multiplexed brain imaging (Aim3). These studies will lay the foundation for the development of connectomics and establish new paradigms for multimodal imaging. My career goal is to run an academic lab that develops essential methodologies for brain research. The proposed work that focuses on the most urgent needs of connectomics will become a mainstay for my independent research and allow me to integrate the newly acquired knowledge in neurobiology, biochemistry, and microscopy with my interdisciplinary training in chemistry and materials science. The unique environment at Lichtman lab will put me in a privileged position in order to pursue my career aspirations. I have developed a detailed training plan with my mentor, Prof. Jeff Lichtman, to help me transition to independence. I will meet regularly with him to discuss research progress, strategies for grant writing, student mentorship, and lab management. I will oversee the work of a graduate student to practice my mentorship skills. To broaden my scientific network and establish future collaborations, I will present my work in workshops, connectomics meetings, SfN and ACS annual meetings. As a member of the Harvard Department of Molecular and Cellular Biology, I will have access to leaders in neuroscience, molecular biology, cell biology, and biochemistry, as well as cutting-edge core facilities. The BRAIN Initiative Diversity K99/R00 will provide me the funding required to initiate an ambitious research plan to tackle the outstanding challenges surrounding brain studies.

项目摘要动物的神经系统由大量突触连接的神经元组成。由此产生的神经网络是动物行为的基础，并有助于学习许多物种的信息。在人类中，神经网络的错误可能导致行为，学习和思想。由于所有这些原因，了解发展，组织，神经回路的破坏至关重要。连接组学的目的是制作和研究地图神经系统内神经元连接的。连接组研究需要自动图像获得覆盖大量大量放大倍数以解决突触的大量大量的脑组织图像的获取以及从这些图像生成接线图的方法。但是连接图本身是然而，不足以解释大脑功能。其他信息，例如分子需要从同一神经系统中提取神经元的身份。这个主要目标建议是开发整个小鼠大脑和其他大脑样品的重金属染色对于完整连接组的体积电子显微镜映射（AIM1），生成了一个库微型蛋白质粘合剂，用于相关的光和电子显微镜成像到桥接与神经元细胞类型研究（AIM2）的连接组学，并扩大了X射线显微镜的使用多路复用大脑成像（AIM3）。这些研究将为发展奠定基础连接组并建立用于多模式成像的新范式。我的职业目标是运行一个学术实验室，该实验室为大脑研究开发基本方法。侧重于最紧急连接组学需求的拟议工作将成为中流台对于我的独立研究，使我能够整合新获得的神经生物学知识，我在化学和材料科学方面的跨学科培训进行了生物化学和显微镜。利希特曼实验室的独特环境将使我处于特权的位置，以追求我职业愿望。我已经与导师杰夫·利希曼（Jeff Lichtman）教授制定了详细的培训计划帮助我过渡到独立。我将定期与他见面，讨论研究进度，授予写作，学生指导和实验室管理的策略。我将监督一个研究生练习我的指导能力。扩大我的科学网络并建立未来的合作，我将在研讨会，连接组会议，SFN和ACS上介绍我的工作年度会议。作为哈佛分子和细胞生物学系的成员，我将可以进入神经科学，分子生物学，细胞生物学和生物化学的领导者以及尖端的核心设施。大脑倡议多样性K99/R00将为我提供所需的资金制定雄心勃勃的研究计划，以应对围绕大脑研究的杰出挑战。