This project will identify new principles by which communication between tissues affects the oxidation of proteins as a function of age in a model organism, a roundworm. The simultaneous oxidation of proteins is increasingly recognized as an important means of coordinating protein function both within and between cells. Specifically, the oxidation of cysteine residues (an amino acid within proteins) plays an important role in regulating proteins involved in fat metabolism, gene expression, and cell shape. However, little is known about how cysteine oxidation is coordinated between cells because it has been difficult to measure oxidation non-destructively in live organisms. Recent innovations in imaging of cysteine oxidation in living animals enable the researcher to fill this critical gap in knowledge, which currently limits understanding of how multicellular organisms coordinate diverse cellular processes. It is expected that the proposed research will have a wide-reaching impact on aging, metabolism, inflammation, and other fields where physiological processes are influenced by protein oxidation. The project integrates research and education by providing research and learning opportunities on the science of aging for students in grades 6-12, undergraduate and graduate students, and the public. These opportunities include laboratory research experiences and educational leadership development for undergraduates, research modules that engage hundreds of new undergraduates in cutting-edge research experiences, and an open classroom that will outreach to hundreds of senior citizens and establish inter-generational relationships between them and students.
Cysteine oxidation disrupts enzyme catalysis and is an important regulatory mechanism for hundreds of proteins that control a wide variety of cellular processes. Little is known about the intercellular signaling pathways that can affect the oxidation of these proteins in a concerted manner. The objective of this project is to determine how intercellular signaling pathways regulate cytosolic protein oxidation in specific target tissues and with aging, using the nematode Caenorhabditis elegans as a tractable model system. Protein oxidation will be measured with single-cell resolution in live animals, using a genetically-encoded, fluorescent sensor. The research questions addressed are: (1) How do sensory neurons regulate protein oxidation in distant target tissues? (2) How does local intercellular signaling regulate protein oxidation in specific target tissues? (3) How is the trajectory of protein oxidation with aging determined by intercellular signaling? This project will provide research opportunities in the science of aging for elementary to graduate level students, develop new courses and authentic research modules for undergraduate students, and improve public awareness and knowledge about aging science by offering courses designed to engage senior citizens.
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.
