Elucidating 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 Impact The 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.
