Genetic Resource for Optical Signaling

光信号遗传资源

基本信息

批准号：
8898204
负责人：
Michael I. Kotlikoff
金额：
$ 64.34万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8898204
关键词：
1,2-diacylglycerol Adoption Affinity Alar Area Bacterial Artificial Chromosomes Biological Process Biology Biosensor Cardiopulmonary Cardiovascular Diseases Cardiovascular system Cells Communities Complex Coupled Coupling Cyclic AMP Diglycerides Disease Endothelial Cells Endothelium Engineering Event Funding Gene Transfer Techniques Generations Genetic Grant Heart Diseases Hematological Disease Image Investigation Knowledge Laboratories Light Lung diseases Mammals Mediating Methods Molecular Mouse Protein Mouse Strains Mus Muscle Tonus Mutant Strains Mice Myocardial Infarction Myocardium National Heart, Lung, and Blood Institute Optics Physiological Principal Investigator Production Proteins Pulmonary Heart Disease Pulsar Reagent Research Research Personnel Resources Science Scientist Second Messenger Systems Signal Transduction Smooth Muscle Smooth Muscle Myocytes Specific qualifier value Technology Time Tissues Transgenes Transgenic Mice Vascular Diseases Vasodilation Virus Diseases abstracting calcium indicator combinatorial cost effective design detector embryonic stem cell experience fluorescence imaging genetic resource in vivo induced pluripotent stem cell interest neural circuit optical sensor optogenetics promoter receptor research study second messenger sensor tool transgene expression

项目摘要

DESCRIPTION (provided by applicant): Advances in genetically encoded sensor and effector proteins have introduced unprecedented opportunities for the study of complex biological processes in vivo that provide an opportunity to rapidly advance knowledge critical to the understanding and treatment of cardiovascular and cardiopulmonary diseases. These optical tools have not been widely exploited due to the lack of available transgenic mouse lines expressing these reagents in relevant tissues. Such genetic reagents could be easily and efficiently deployed for the study of NHLBI relevant biology and disease, transforming the capacity of NHLBI scientists. We propose the creation of purpose -designed mouse lines that express Ca2+ sensors and Optogenetic cell activators in NHLBI relevant tissues. The Genetic Resource for Optical Signaling will consist of 50 mouse lines designed for combinatorial crosses enabling the co-expression of sensors and effectors, or red and green Ca2+ sensors in interacting lineages. This strategy will enable the combination of two synergistic technologies (Ca2+ sensors and optogenetic proteins) through simple, high-yield crosses that constrain expression of the transgene to cells of interest. As such, the resource will enable NHLBI researchers to conduct experiments not otherwise possible in a cost effective and highly efficient manner, accelerating the use of optical genetic tools and markedly accelerating scientific discovery. The Genetic Resource for Optical Signaling (GROS) will create and validate the lines, communicate their availability, and permanently bank them for distribution to the scientific community following the funding period. RELEVANCE: We will create a resource that advances cardiovascular and cardiopulmonary science consisting of lines of mice expressing 3rd generation optical sensors and cell activators in lineages of relevance to NHLBI science. These mice will be fully characterized and made available to the community, creating permanently available reagents that will markedly enhance the capabilities of hundreds of scientists. (End of Abstract)

描述（由申请人提供）：遗传编码的传感器和效应子蛋白的进展引入了前所未有的机会，用于研究体内复杂的生物学过程，提供了一个机会，可以快速促进知识，以了解对心血管和心脏肺部疾病的理解和治疗至关重要。由于缺乏可用的转基因小鼠系在相关组织中表达这些试剂，因此未广泛利用这些光学工具。这种遗传试剂可以轻松有效地部署，以研究NHLBI相关的生物学和疾病，从而改变NHLBI科学家的能力。我们提出了在NHLBI相关组织中表达CA2+传感器和光遗传细胞活化剂的目的设计的小鼠系的创建。光学信号传导的遗传资源将由50个小鼠线组成，专为组合杂交，使传感器和效应子的共表达，或相互作用的谱系中的红色和绿色Ca2+传感器。该策略将通过简单的高收益交叉限制了转基因表达对感兴趣的细胞的表达，从而使两种协同技术（Ca2+传感器和光遗传学蛋白）结合在一起。因此，该资源将使NHLBI研究人员能够以具有成本效益且高效的方式进行其他实验，从而加速使用光学遗传工具并显着加速科学发现。光信号传导（GRO）的遗传资源将创建和验证线路，传达其可用性，并在资助期间永久将其分配给科学界。相关性：我们将创建一种资源，以促进心血管和心肺科学的发展，该科学由与NHLBI科学相关的谱系中表达第三代光学传感器和细胞激活剂的小鼠线组成。这些小鼠将得到充分的特征并提供给社区，并创建永久可用的试剂，从而显着增强数百名科学家的能力。（抽象的结尾）