PROJECT ABSTRACT Research over the past two decades has led to the discovery of mutations that cause rare autoinflammatory diseases and advanced our understanding of common autoimmune diseases. Further, the understanding of the complex mechanisms underlying autoinflammatory and autoimmune diseases has also expanded at a rapid pace. We now have a better understanding of the interplay between key components of innate and adaptive immune systems and the pathways involved. These advances were driven by improvements in sequencing technologies, single-cell genomic approaches, spatial transcriptomics, proteomics, metabolomics, and high- resolution imaging. Additionally, improved animal models of human disease, innovative stem cell and organoid systems, and a new appreciation for the microbiome's influence on immune reactivity have fueled progress. These discoveries provide a framework for identifying new targets to treat a wide range of autoimmune and inflammatory diseases. Despite these advances, immune-mediated diseases are reaching epidemic proportions. To address this emerging health crisis, we must train the next generation of scientists to capitalize on these insights and develop novel therapeutic strategies for autoinflammatory and autoimmune diseases. The Training in the Molecular Basis of Autoimmunity and Autoinflammation (AATG) T32 prepares predoctoral students to become future scientific leaders by providing a strong foundation in the basic principles of innate and adaptive immunity. The AATG program brings together 34 investigators from ten departments, representing a broad spectrum of research backgrounds and expertise, ranging from basic research to drug discovery, who are engaged in basic and translational, disease-oriented research focusing on autoimmune/autoinflammatory conditions. challenging Our faculty are either current or up-and-coming leaders in their fields, which will foster intellectually discourse, a firm understanding and working knowledge of the principles and applications of cutting- edge research technologies, and exciting thesis research. The goal is to provide our trainees with the skill set to succeed as independent and creative investigators in the constantly evolving world of biomedical research. The AATG provides predoctoral students with critical career skills to effectively communicate their discoveries, and students will be strongly encouraged to participate in regional, national and international meetings. The training curriculum will also emphasize scientific rigor, methods for appropriate data management/analysis/ validation, biosafety, conflict resolution, and ethical conduct. The AATG physician-scientists will enable our trainees to engage with leaders in adjacent clinical sites to better understand the diseases we hope to cure. The AATG faculty further serve as role models and provide attractive opportunities for women, economically disadvantaged and underrepresented minorities to encourage the pursuit of careers in basic scientific research. These goals will help meet future challenges and societal needs in biomedical research.

PROJECT NARRATIVE In the past two decades, we have seen a paradigm shift in our understanding of the mechanisms underlying autoimmune and autoinflammatory diseases. To continue generating key insights and developing novel therapeutic strategies will require the next generation of scientists to have broad, multidisciplinary understanding and training in the latest advanced technologies. The Training in the Molecular Basis of Autoimmunity and Autoinflammation develops predoctoral investigators in these crucial areas by bringing together highly skilled and collaborative training faculty from multiple disciplines, with the ultimate goal of developing effective treatments, and eventually cures, for these debilitating diseases.