With this award, the Chemistry of Life Processes program is funding Dr. Scott Eagon of California Polytechnic State University-San Luis Obispo to developing new chemical probes for kinase enzymes. Kinases are a class of proteins found throughout human cells and play a central role in regulating cell communication and growth. Kinases are so critical, in fact, that there are more than 500 different types found in the body. When kinases stop functioning properly, this leads to a variety of negative effects including inflammation, cardiovascular disease, and cancer. Despite their critical role in maintaining the health of cells, most kinases remain poorly understood. These chemical probes are tools that allow Dr. Eagon and his team of undergraduate researchers to better understand two key kinases named STK16 (serine/threonine kinase 16) and CK2 (casein kinase 2). These two kinases are thought to be involved in cellular pathway regulation and may be dysfunctional in some forms of cancer. These chemical probes allow for the systematic testing of STK16 and CK2 to better understand their roles in cellular signaling. Undergraduate researchers participating in this project acquire a broad range of knowledge and skills in cell biology, biochemistry, and organic chemistry. Moreover, this project has a two-fold outreach program aimed at both undergraduate courses and local K-12 students. This will provide undergraduates with a chance to learn computational docking and molecular visualization software, while also providing K-12 students the opportunity to think like scientists in an effort to stimulate their scientific curiosity. K-12 students are also exposed to a college experience, to encourage them to pursue future careers in science, technology, engineering, and mathematics (STEM) fields. The PI will engage a large and diverse group of undergraduate and K-12 students in chemical biology topics and, in this way, contribute to inspiring the next generation of research scientists.
The goal of this project is to identify potent and selective chemical probes targeting poorly understood kinases in order to interrogate the function of these critical cellular regulators. Specifically, probes targeting the ATP (adenosine triphosphate)-binding pocket of human kinases STK16 and CK2 are synthesized based on preliminary lead compound scaffolds that have already been identified. This project also provides opportunities for undergraduate students to gain research experience and has the potential to facilitate our understanding of understudied kinase pathways and how they influence cell growth and development. Another key aspect of this proposal is the adoption of an open-source policy by making all probes and cellular data publicly available and free to the community with no restrictions on use. Successfully developed probes will be incorporated into the Kinase Chemogenomic Set (KCGS) and are to be made available to the research community in order to maximize research impact.
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.
