Research Starter Grant: Integrated Protein Design for Non-natural Electron-Transfer Systems

Yale University, New Haven CT

Investigators

Abstract

Intellectual Merit Life is inextricably linked to a process called electron-transfer (ET). ET reactions are central to bioenergetic processes, such as hydrogen production, photosynthesis, and cellular respiration. ET in living organisms is analogous to an electrical current that powers a household appliance in that there must be a source of electrons (an outlet) and a pathway for the current to follow in order to supply energy to the electrical device so that it is able to function. The ability to understand and control biological machinery - i.e., the source and pathways - involved in the process of electron-transfer will allow the development of microscopic electronic devices that could be used to benefit society. Contrary to the general understanding of electron-transfer (ET) in naturally occurring phenomena, the express design of protein-based ET systems - i.e., elements that will facilitate the production of higher-order devices for biomedical and bio-industrial applications - presents a significant challenge. To resolve this deficiency, it is hypothesized that a central theoretical approach (classical ET theory) must be integrated with existing protein design procedures to create ET systems with tailored functions. The overarching goal of this research is to expand the understanding of general features of electron-transfer in biological systems as well as to generate the fundamental framework for the design of ET-functional biomolecules. To accomplish this, a combination of experimental and computational approaches, informed by theory, will be employed. This integrated multi-disciplinary framework will be used to produce singular synthetic material capable of interacting with naturally occurring functional elements and non-natural materials alike. This dynamic range of interactions will facilitate an array of novel and useful interfaces capable of meaningful communication and logical operations at the molecular level. Likewise, the ability to produce viable bioelectronics will advance the understanding of fundamental life processes and expand the use of designed biomolecules as the building blocks of higher-level functional devices (e.g., biomaterial-based electronic circuitry, biofuel cells that use natural substances in the body to generate energy to power implantable devices, and advanced prosthetics). Broader Impact This research project will facilitate the development of successful scientific peers by providing a helpful, encouraging, and productive research environment in which research methods and scientific output can be critically evaluated in a supportive and constructive manner. This project will also strongly encourage and support the participation of underrepresented graduate, undergraduate, and career high school students in research. Aspiring scientists that participate in this program will benefit from the very unique opportunity to receive equal training in experimental and computational approaches. Moreover, this research will enhance our current infrastructure for research and education through (i) extensive collaborations and (ii) integration of this research into the Yale undergraduate and graduate curricula via new interdisciplinary course modules.