With this award, the Chemistry of Life Processes Program supports the group of Dr. Raphael M. Franzini from the University of Utah in a collaboration with Dr. Randall Peterson from the University of Utah to develop new chemistries to study and manipulate biomolecules in cells. Countless biological components are precisely orchestrated during cellular processes. One such process is the interaction of proteins with each other during cell signaling events. Studying these processes and events with high precision often requires activation of specific biological components at specific times during a measurement. One way to achieve this goal is to use chemical reactions. However, in order to be practical under typical biological conditions, such a chemical reaction needs to be completed in a few minutes. To obtain such short reaction times, the size of molecules involved in the reaction should be as small as possible to minimize their interference with the large biomolecules in the system. This award funds the development of new chemistries that meet these requirements and provides formal research training opportunities for undergraduate and graduate students toward becoming leaders in chemistry and biology. An integral part of the research program is the establishment of the Summer Experience Advancing Research in Chemical Biology (SEARCH) program that provides research and mentoring opportunities to encourage high school students to enter a career in a science, technology, engineering, and mathematics (STEM) field.
The research project explores the bioorthogonal chemistry of isocyanides to enable the rapid uncaging of molecules of interest in cells. The isocyano group is unique because although consisting of only two atoms it readily undergoes bioorthogonal reactions. The project advances isocyano-based groups that can be removed by exposure to tetrazines, which are another type of bioorthogonal moiety. Particular goals are to make the release reaction faster, the masking groups smaller, and to reduce the tetrazine concentration needed for the reaction to occur. The chemistry is used to study the activity of proprotein convertases during the early embryogenesis of zebrafish with spatial and temporal resolution.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.