CAREER: Investigating and Educating: Novel Mechanisms in Biology

蛋白质必须采用正确的折叠结构才能发挥全部功能。 对于一些蛋白质，翻译后修饰对蛋白质的结构和功能都有巨大的影响。 蛋白质功能的结构调节控制在生物学的许多方面已经得到了很好的建立，并且通常是生命所必需的信号转导事件中的关键控制步骤，例如对营养素和应激的响应，细胞周期进展和增殖。 然而，蛋白质结构的意外改变可能是有害的。 错误折叠的蛋白质通常与不可逆的功能丧失和疾病有关，而不是调节。 在这个项目中，一组蛋白质将被调查的能力，采取一种特定类型的“错误折叠”状态（朊病毒构象）作为一种手段的调节。 一组朊病毒蛋白质可能已经进化出产生构象重大变化的内在能力，作为调节生命所必需的中心过程：蛋白质合成的手段。 有趣的是，朊病毒蛋白质的复杂网络可以调节酵母中的蛋白质合成。 这项研究将集中在阐明这种类型的监管机制的基本原则。 这个CAREER项目的更广泛的影响将包括在朊病毒生物学的本科生的培训，以及在研究项目中的代表性不足的少数民族高中生的包容性。

Proteins must adopt the correct folded structure for full functionality. For some proteins, post-translational modifications have a tremendous impact on both the structure and the function of the protein. Structural regulatory control of protein function has been well established in many facets of biology and is often a key control step in signal transduction events that are essential for life, such as the response to nutrients and stresses, cell cycle progression, and proliferation. However, unexpected alterations in protein structure can be detrimental. Misfolded proteins are frequently associated with irreversible loss-of-function and disease instead of regulation. In this project, one group of proteins will be investigated for their ability to adopt a specific type of "misfolded" state (prion conformation) as a means of regulation. A group of prion proteins may have evolved with the intrinsic ability to produce major changes in conformation as a means of regulation of a central process essential for life: protein synthesis. Interestingly, a complex network of prion proteins may regulate protein synthesis in yeast. This research will focus on elucidating the underlying mechanistic principles of this type of regulation. The broader impact of this CAREER project will include training of undergraduate students in prion biology, as well as inclusion of under-represented minority high school students in the research project.