Grant: Operating Grant

Living organisms must be able to respond to changes in their environment. At the cellular level, part of the adaptation to environmental changes involves regulating various protein and enzyme levels. This regulation is accomplished by a set of enzymes that tag specific proteins with the small protein ubiquitin, in a process known as the protein ubiquitination cycle. Proteins that are regulated by this cycle are involved in life processes such as growth, division, immunity, and DNA repair. Thus, the ubiquitination cycle has been targeted for development of therapeutics for the treatment of cancer. The objectives of our research are to determine the chemical principles underlying the attachment of ubiquitin to other proteins by applying the tools of modern biochemistry and computational chemistry. In addition, we use magnetic resonance spectroscopy to determine how proteins specifically recognize the ubiquitin tag. The basic knowledge we gain through this research is a fundamental requirement not only for understanding the cellular function of the ubiquitination cycle, but to also help develop rational therapies, in the long term, for associated diseases such as cancer.