Biological systems are extraordinarily complex yet organized on both the spatial and temporal levels, and if we are to study, perturb, engineer, or heal biological entities, we must be able to precisely and selectively manipulate key players in such systems. Thus, a central challenge in the basic and engineering sciences is the design of environmentally responsive agents that respond to our external cues on-demand, to allow us to control, interrogate, and manipulate biological systems. Among the potentially exploitable external stimuli, light is a particularly desirable actuator, as it enables high resolution in space and in time with minimal disturbance to biological systems.
Some of the key players in biological systems are called proteins. Proteins are produced from 20 natural elements called amino acids. These 20 building blocks have enabled much of the diversity and function of proteins and has allowed them to perform a multitude of biological roles. To manipulate such proteins and understand their function, we seek to expand biology beyond the standard set of 20 amino acids by encoding light-responsive synthetic amino acids. However, the addition of new chemical groups in proteins by incorporation of synthetic amino acids remains a laborious task that often fails due to inadequate engineering of the protein-making machinery. Thus, working within the confines of current technologies both hinders efficient incorporation of light-responsive synthetic amino acids, as well as the types of light-responsive groups that can be incorporated.
The overall objective of this study is to develop a technology for efficient incorporation of light-responsive synthetic amino acids and to apply this technology to engineer customized light-responsive formulations for applications in drug delivery, for cell and tissue engineering, and for analyzing and manipulating biological processes. To achieve this we are developing genome engineering tools to generate a platform for the selection of protein-making machinery that are capable of efficiently incorporating a variety of light-responsive chemical groups into proteins. These tools will allow us, and many other laboratories to design light-responsive proteins, and to elucidate their function and manipulate their activity in a various biological systems.
