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上。我们有悠久的历史 对这些蛋白质和它们用来检测的线性四吡咯(BLIN)发色团感兴趣 灯。这个超家族的成员控制着植物的生长和发育(种子萌发， 光形态建成、遮荫回避和开花等过程)，使 光敏色素是提高农业效益的重要研究对象 面对不断增加的人口对粮食的需求。这个家庭的其他成员允许 细菌移动、形成生物膜或调整其新陈代谢以响应光环境。 光敏色素和蓝藻色素(CBCRs)是生物体中的两个蛋白质家族。 光敏色素超家族，能够探测到近紫外光和 近红外，包括红光和远红光波长，最适合于在 哺乳动物组织。因此，基础研究要了解光敏色素的多样性、作用机理 深入研究其在植物、藻类和细菌中的功能，以及开发新的成像工具 符合NIGMS的使命。 拉加里亚斯实验室的研究利用了在这一领域出现的自然多样性 进化过程中的超级家族。我们试图了解使这些蛋白质 感知不同颜色的光，显示出明亮的荧光或在 光状态，将温度或pH等信号与光相结合，并报告这一点 信息发送到细胞。在这项研究过程中，我们还开发了有用的试剂 包括荧光光敏色素、结构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 这些蛋白质对远红光和近红外光的影响。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，可应用于 现有试剂和系统允许新的成像应用，合成生物学的多路传输 响应不同颜色的系统，或特定于特定目标的组织应用 用光而不是基因启动子激活的。这些目标与我们的总体目标非常吻合 了解这一家族的光化学、生物物理和生物学过程 通过开发一种可能在生物医学成像和合成生物学方面取得进展的技术 知识库，用新的试剂改进基本方法，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.