Understanding and leveraging molecular diversity within the phytochrome superfamily

理解和利用光敏色素超家族中的分子多样性。 我们的建议集中在光敏色素超家族的光感受器。我们长期以来 感兴趣的是这些蛋白质和线性四吡咯（胆色素）发色团，他们用来检测 光该超家族的成员控制植物的生长和发育（种子萌发， 光形态建成、避荫和开花等过程）， 光敏色素是提高农业生产效率的重要研究对象， 面对不断增长的人口对粮食的需求。这个家庭的其他成员允许 细菌移动，形成生物膜，或调整它们的新陈代谢以响应光环境。 光敏色素和蓝细菌色素（CBCR），两个家庭的蛋白质在 光敏色素超家族，能够检测到近紫外线和 近红外，包括红色和远红色波长，最适合成像， 哺乳动物组织因此，基础研究，以了解光敏色素的多样性， 在植物，藻类和细菌中的功能，以及新成像工具的开发 符合NIGMS的使命。 Lagarias实验室的研究利用了这一领域出现的自然多样性， 进化过程中的超家族我们试图了解这些蛋白质 来感知不同颜色的光，要么表现出明亮的荧光， photostates，整合信号，如温度或pH与光，并报告这一点 信息到细胞。在这项研究的过程中，我们还开发了有用的试剂 包括荧光光敏色素、组成型活性植物光敏色素和光敏色素- 零植物在接下来的五年里，我们设想在理解检测方面取得进一步的进展 远红光和近红外光的信号。我们希望学习如何“重新调整”颜色- 一系列光敏色素和CBCR的传感机制，一个洞察力，适用于 现有的试剂和系统允许新的成像应用，合成生物学的多路复用 系统，以响应不同的颜色，或组织的具体应用，其中特定的目标是 光而不是基因启动子激活。这些目标与我们的总体目标非常吻合， 了解这个家族的光化学，生物物理和生物过程， 通过开发一种生物医学成像和合成生物学技术， 知识基础，用新试剂改进基本方法，并利用新的 技术.

Understanding and leveraging molecular diversity within the phytochrome superfamily. Our proposal focuses on the phytochrome superfamily of photoreceptors. We have a longstanding interest in these proteins and in the linear tetrapyrrole (bilin) chromophores they use to detect light. Members of this superfamily control growth and development of plants (seed germination, photomorphogenesis, shade avoidance, and flowering, among other processes), making phytochromes important research targets for enhancing agricultural efficiency to meet the demand for food in the face of increasing human population. Other members of this family allow bacteria to move, form biofilms, or adjust their metabolism in response to the light environment. Phytochromes and cyanobacteriochromes (CBCRs), the two families of proteins in the phytochrome superfamily, are able to detect every color of light between the near-ultraviolet and the near-infrared, including red and far-red wavelengths that are optimal for imaging in mammalian tissue. Thus, basic research to understand phytochrome diversity, the mechanisms underlying its function in plants, algae, and bacteria, and development of new imaging tools well fits the mission of NIGMS. Research in the Lagarias lab leverages the natural diversity that has arisen in this superfamily during evolution. We seek to understand the mechanisms that allow these proteins to sense different colors of light, to either exhibit bright fluorescence or switch between photostates, to integrate signals such as temperature or pH with light, and to report this information to the cell. In the course of this research, we have also developed useful reagents including fluorescent phytochromes, constitutively active plant phytochromes, and phytochrome- null plants. In the next five years, we envision making further progress in understanding detection of far-red and near-infrared light by these proteins. We expect to learn how to “re-tune” the color- sensing mechanisms of a range of phytochromes and CBCRs, an insight which be applied to existing reagents and systems to allow new imaging applications, multiplexing of synthetic biology systems to respond to different colors, or tissue-specific applications in which specific targets are activated with light rather than with gene promoters. These goals fit well with our overall goals of understanding of the photochemical, biophysical, and biological processes of this family and potentially yield advances in biomedical imaging and synthetic biology via development of a knowledge base, improving fundamental methods with new reagents, and leveraging new technologies.