PKA SPATIOTEMPORAL DYNAMICS DRIVE AUTOPHAGY AND MITOCHONDRIAL PHENOTYPES IN CELLULAR SENESCENCE - PROJECT SUMMARY THIS PROJECT WILL INVESTIGATE HOW COMPARTMENTALIZED PROTEIN KINASE A (PKA) SIGNALING DYNAMICS INFLUENCE THE INDUCTION AND HETEROGENEITY OF SENESCENT CELL FATES. USING LIVE-CELL BIOSENSORS, HIGH-THROUGHPUT TIME-LAPSE IMAGING, AND MACHINE LEARNING-BASED SINGLE-CELL ANALYSIS, THE PROPOSED RESEARCH WILL CHARACTERIZE SUBCELLULAR PKA ACTIVITY TRAJECTORIES IN RESPONSE TO SENESCENCE-INDUCING STIMULI AND IDENTIFY PREDICTIVE FEATURES OF CELLULAR AGING. INSIGHTS GAINED WILL PROVIDE A MECHANISTIC FRAMEWORK FOR UNDERSTANDING HOW DYNAMIC SIGNALING INPUTS SHAPE SENESCENT PHENOTYPES AND MAY UNCOVER TARGETS FOR SELECTIVE SENESCENCE MODULATION. THE FELLOWSHIP TRAINING PLAN EMPHASIZES DEVELOPMENT OF COMPUTATIONAL MODELING, MACHINE LEARNING, AND SINGLE- CELL BIOINFORMATICS SKILLS, ALONGSIDE CONTINUED GROWTH IN EXPERIMENTAL CELL BIOLOGY AND QUANTITATIVE IMAGING. TRAINING ACTIVITIES WILL INCLUDE COURSEWORK, MENTORED RESEARCH, STRUCTURED CAREER DEVELOPMENT, AND PARTICIPATION IN INTERDISCIPLINARY SEMINARS AND JOURNAL CLUBS. RESEARCH AND TRAINING WILL BE CONDUCTED IN THE LABORATORY OF DR. NAN HAO AT UC SAN DIEGO, A LEADING CENTER FOR SYSTEMS BIOLOGY AND AGING RESEARCH. THE TRAINING ENVIRONMENT INCLUDES ACCESS TO STATE-OF-THE-ART IMAGING AND COMPUTATIONAL RESOURCES, CO-MENTORSHIP BY EXPERTS IN AGING AND TRANSCRIPTOMICS, AND PARTICIPATION IN COLLABORATIVE NETWORKS THROUGH THE SAN DIEGO NATHAN SHOCK CENTER AND REGIONAL RESEARCH INSTITUTES.