With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Y. George Zheng from University of Georgia to investigate novel functions of enzymes called KATs. Previously the actions of KATs were known to control genes in an on-off fashion. Recent discoveries revealed new biological roles for KATs nearly every place in the cell, beyond the effect on genes. Functions of KATs are far more complex than previously regarded with impacts on multifaceted biological processes, including promoting entirely new chemical reactions. In this project, the PI designed a series of biochemical and cellular experimental studies to discover and characterize new functions of the major KAT enzymes. A highly multidisciplinary approach is proposed to dissect novel KAT functions. This pursuit is directly related to the PI's efforts in the training of graduate and undergraduate students in chemical biology and biochemistry. By undertaking these projects, students will learn how to apply advanced technologies to resolve key biological research problems. This project also integrates outreach activities to introduce high school students to the science of enzyme biochemistry. These research-related educational efforts are important to prepare next-generation scientists in chemical and biological sciences.
The research project undertakes the development and application of new chemical biology tools to profile cellular substrates and new functions of the major KAT enzymes, with the goal of significantly advancing protein acylation research. The PI refines and applies a bioorthogonal labeling technology to investigate substrate profiles of the major KATs at the proteomic level. The PI and coworkers also investigate a novel lysine acylation mark in histones and non-histone proteins that they recently discovered. In these experiments, the team identifies enzymes that catalyze the addition and removal of the novel modification mark. The proposed research has great potential to generate new chemical tools for KAT activity investigation, offers a systematic view of KAT substrate distribution in the cell, provides a mechanistic understanding of KAT functions, and to a broader level, advances the knowledge of posttranslational modifications in chromatin remodeling, metabolic pathways, and signal transduction.
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.
