Genetic Resource for Optical Signaling

描述（由申请人提供）：基因编码的传感器和效应蛋白的进展为研究体内复杂的生物过程带来了前所未有的机会，为快速推进对理解和治疗心血管和心肺疾病至关重要的知识提供了机会。由于缺乏在相关组织中表达这些试剂的可用转基因小鼠品系，这些光学工具尚未被广泛利用。这种基因试剂可以很容易和有效地用于NHLBI相关生物学和疾病的研究，改变NHLBI科学家的能力。我们建议建立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，这些小鼠品系被设计用于组合杂交，使得传感器和效应器或红色和绿色Ca2+传感器在相互作用的谱系中共表达。该策略将使两种协同技术（Ca2+传感器和光遗传学蛋白）能够通过简单、高产的杂交结合，所述杂交将转基因的表达限制在感兴趣的细胞中。因此，该资源将使NHLBI的研究人员能够以具有成本效益和高效的方式进行实验，加速光学遗传工具的使用，并显着加快科学发现。光信号遗传资源（GROS）将创建和验证这些线，传达它们的可用性，并永久保存它们，以便在资助期后分发给科学界。 相关性：我们将创建一个促进心血管和心肺科学的资源，包括表达与NHLBI科学相关的第三代光学传感器和细胞激活剂的小鼠品系。这些小鼠将被充分表征并提供给社区，创造永久可用的试剂，这将显着提高数百名科学家的能力。(End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)