CAREER: Reactivity of Selenoproteins

解释酶——加速化学反应的蛋白质——控制化学反应的机制是当代生命科学中最令人兴奋的挑战之一。为了理解细胞的内部工作原理，理解酶是如何微调它们与特定反应伙伴结合的能力并只加速所需的反应是特别重要的。本研究的重点是利用稀有氨基酸硒代半胱氨酸的酶家族的独特化学。这些硒酶是高效率的，并表现出一种独特的能力，可以避免活性氧（即在能源生产过程中形成的有毒化学物质）的失活。该项目利用生物物理方法研究这些特性及其分子起源，重点关注硒酶之间的共性。因此，本研究的智力价值来自于理解硒酶的特殊化学作用，以及它如何补充和整合常用的基于硫的丰富的氨基酸半胱氨酸的化学作用。它将揭示控制硒酶功能的基本原理，更一般地说，酶的操作和调节。更广泛的影响这个项目的更广泛的影响来自于在课堂和实验室中创造一个研究和教育环境，强调培养学生的系统和逻辑推理能力。此外，它旨在培养学生运用这些工具独立寻找和评估信息的信心。理想是分享科学的乐趣和责任。这是通过扩展生物化学课程，将主动学习和以探究为基础的教学方法结合起来，以强调学习概念来实现的。我们的目标不仅是让来自不同学科的广大读者更好地为未来的职业生涯做好准备，而且还要提高他们对科学及其对当代生活的贡献的兴趣。为了多样化和扩大对科学的参与，一个独特的暑期项目将为有身体和学习障碍的大学生提供专业的职业建议、交流机会，以及面临类似逆境的科学家的职业道路的例子。目标是准备和鼓励这些大学生，他们通常离开科学，追求科学和工程的研究生学习。

Intellectual MeritElucidating the mechanisms by which enzymes - proteins that accelerate chemical reactions-- control chemical reactivity is among the most exciting challenges in contemporary life sciences. To comprehend cells' inner workings it is particularly important to understand how enzymes fine tune their ability to bind specifically their reaction partners and accelerate only the desired reaction. This research focuses on the unique chemistry of a family of enzymes that utilizes the rare amino acid selenocysteine. These selenoenzymes are highly efficient and exhibit a unique capacity to escape inactivation by reactive oxygen species, i.e. toxic chemicals that are formed during energy production. The project utilizes biophysical approaches to study these properties and their molecular origins in detail by focusing on commonalities among the selenoenzymes. Thus, the intellectual merit of this research arises from understanding the specialized chemistry performed by selenoenzymes and how it supplements and integrates with the commonly used sulfur-based chemistry of the abundant amino acid cysteine. It will reveal the fundamentals that govern selenoenzymes function and, more generally, enzyme operation and regulation.Broader ImpactThe broader impact of this project arises from the creation of a research and educational environment -both in the classroom and in the laboratory- that emphasizes the training of the students' systematic and logical reasoning skills. Furthermore, it seeks to nurture the students' confidence to apply these tools to independently seek and evaluate information. The ideal is to share the pleasures and responsibilities of science. This is achieved by expanding the biochemistry curriculum to incorporate active learning and inquiry-based teaching methods to emphasize learning concepts. The goal is not only to better prepare a wide audience from many disciplines for their prospective careers, but to also enhance their interest in science and its contribution to contemporary life. To diversify and expand participation in science, a unique summer program will provide college students with physical and learning disabilities with specialized career advice, networking opportunities, and examples of career paths of scientists who faced similar adversities. The goal is to prepare and to encourage these college students, who typically leave the sciences, to pursue graduate studies in science and engineering.