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。对于一些蛋白质来说，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控在生物学的许多方面都得到了很好的证实，并且往往是生命所必需的信号转导事件的关键控制步骤，如对营养和胁迫的反应、细胞周期进展和增殖。然而，蛋白质结构的意外变化可能是有害的。错误折叠的蛋白质经常与不可逆转的功能丧失和疾病有关，而不是与调节有关。在这个项目中，将研究一组蛋白质采用特定类型的“错误折叠”状态(Pron构象)作为调节手段的能力。一组普恩蛋白可能已经进化出了内在的能力，能够在构象上产生重大变化，作为调节生命必不可少的核心过程：蛋白质合成的一种手段。有趣的是，一个复杂的Pron蛋白网络可能会调节酵母中的蛋白质合成。这项研究将集中于阐明这种类型的监管的潜在机制原理。这一职业项目的更广泛影响将包括对本科生进行Pron生物学方面的培训，以及将未被充分代表的少数族裔高中生纳入研究项目。

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.