Genetic Resource for Optical Signaling

光信号遗传资源

基本信息

批准号：
9056610
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/9056610
关键词：
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）：基因编码传感器和效应蛋白的进步为体内复杂生物过程的研究带来了前所未有的机会，这提供了快速推进对心血管和心肺疾病的理解和治疗至关重要的知识的机会。由于缺乏在相关组织中表达这些试剂的转基因小鼠品系，这些光学工具尚未得到广泛利用。这种遗传试剂可以轻松有效地用于 NHLBI 相关生物学和疾病的研究，从而改变 NHLBI 科学家的能力。我们建议创建专门设计的小鼠品系，在 NHLBI 相关组织中表达 Ca2+ 传感器和光遗传学细胞激活剂。光信号遗传资源将由 50 个小鼠品系组成，这些小鼠品系专为组合杂交而设计，能够在相互作用的谱系中共同表达传感器和效应器，或红色和绿色 Ca2+ 传感器。该策略将通过简单、高产的杂交将两种协同技术（Ca2+传感器和光遗传学蛋白）结合起来，限制转基因在感兴趣的细胞中的表达。因此，该资源将使 NHLBI 研究人员能够以具有成本效益和高效的方式进行原本不可能进行的实验，从而加速光学遗传工具的使用并显着加速科学发现。光信号遗传资源（GROS）将创建并验证这些线路，传达它们的可用性，并将它们永久存储起来，以便在资助期结束后分发给科学界。相关性：我们将创建一个促进心血管和心肺科学发展的资源，该资源由表达与 NHLBI 科学相关谱系的第三代光学传感器和细胞激活剂的小鼠品系组成。这些小鼠将被完全表征并提供给社区，创造出永久可用的试剂，这将显着增强数百名科学家的能力。（摘要完）