With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Mary Kay Pflum from Wayne State University to establish several novel assays to probe the activity and substrates of lipid and polynucleotide kinases. These studies are based on the Pflum lab's recent observation that protein kinases promiscuously accept delta-phosphate modified ATP analogs as cosubstrates, a property we term "cosubstrate promiscuity¨. To fully harness the power of cosubstrate promiscuity, this proposal will test the ATP promiscuity of kinases that modify lipid and nucleic acid substrates to reveal the prevalence among the full kinase family. In addition, several novel assays based on the cosubstrate promiscuity of lipid and polynucleotide kinases will be developed. These novel chemical tools will encourage a deeper study of lipids and nucleotides in biological systems, which will broadly enhance biochemistry and cell biology research.
Kinases catalyze the transfer of a phosphate group to substrates, which is a key chemical trigger in metabolism, cell signaling, communication, and adaptation. Moreover, the large kinase family phosphorylates a wide variety of substrates in vivo, including proteins, nucleic acids, lipids, and metabolites. Historically, studies involving kinases have played a prominent role in dissecting the biochemistry and cell biology of many life processes. This research project will significantly impact biochemistry and cell biology research by paving the way for creation of new chemical probes of lipid and nucleic acid biology. This program will also encourage a future generation of scientists by exposing students of all ages to research. Undergraduate and graduate students will perform all experiments in the project, which will expose them as members of the next generation of chemists to multidisciplinary science. At the middle and high school levels, Dr. Pflum will introduce students from the diverse Detroit metropolitan area, particularly women and minorities, to multidisciplinary science and scientific careers through outreach programs. By integrating research and educational activities, this application will broadly impact the community by fostering the next generation of scientists.
