UNDERSTANDING AND LEVERAGING MOLECULAR DIVERSITY WITHIN THE PHYTOCHROME SUPERFAMILY

2021年4月1日 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探测光的线性四吡咯(BLIN)发色团感兴趣。 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 光敏色素是农业增效满足需求的重要研究对象 在面对不断增长的人口时，我们需要食物。这个家族的其他成员允许细菌 对光环境作出反应来移动、形成生物膜或调整其代谢。 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这个超级家族中出现的自然多样性。 在进化过程中。我们试图了解允许这些蛋白质感知的机制 不同颜色的光，以显示明亮的荧光或在光态之间切换，以 将温度或pH等信号与光相结合，并将这些信息报告给细胞。在……里面 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，构成活性的植物光敏色素和光敏色素缺失的植物。在下一个 五年后，我们设想在理解远红外和近红外探测方面取得进一步进展。 由这些蛋白质发出的红外线。我们希望学习如何“重新调整”颜色感知机制 一系列光敏色素和CBCR，这一见解适用于现有的试剂和 允许新的成像应用的系统，合成生物系统的多路传输响应 到不同的颜色，或特定于组织的应用，其中特定的目标被光激活 而不是用基因启动子。这些目标与我们了解的总体目标非常吻合 该家族的光化学、生物物理和生物过程，并有可能产生 通过知识库的开发，生物医学成像和合成生物学的进展， 用新试剂改进基本方法，利用新技术。

April 1, 2021 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.