Innate Immunity Across the Molecular, Cellular, Tissue and Therapeutic - ABSTRACT Support is requested for a Keystone Symposia conference entitled Innate Immunity Across the Molecular, Cellular, Tissue and Therapeutic, organized by Drs. Kate Jeffrey, Ramnik Xavier and Xu Zhou. The conference will be held in Alberta, Canada from April 9–12, 2024. Over three decades ago, Charles Janeway predicted that pathogen sensing was mediated by germline-encoded pattern recognition receptors that detect conserved pathogen-associated molecular patterns (PAMPs). Since then, a multitude of endosomal and cytoplasmic sensors, their ligands and downstream signal transduction pathways that initiate innate immunity have been defined. Emerging techniques such as cellular and spatial transcriptomics are informing us where in the human body, and in what diverse disease contexts, these pattern recognition receptors (PRRs) and associated gene circuits are implicated. Furthermore, metabolic and chromatin analyses are now illuminating acute and chronic adaptation of innate immune cell transcriptional programs. The next frontier in innate immunity will be understanding how innate sensor-ligand interactions, and the individual cellular programs that ensue, work in complex systems of tissue and microorganismal microenvironments. Of particular importance will be grasping innate immunity resolution during homeostasis and how it can be leveraged, or avoided, for the treatment of infectious, autoimmune, neurodegenerative, cardiovascular and oncological diseases. This conference will provide multidisciplinary perspectives on new horizons and unexpected advances in innate immunity. The program will highlight innovative techniques and novel read outs of innate immunity at the molecular, cellular and tissue level and examine the connections of innate immunity with human health. The program will also take a deep dive into clinical aspects of disease and contemporary drug discovery approaches to harness or regulate innate immune using pharmacologic approaches. This conference is designed to be a unique forum for researchers from diverse and traditionally non-overlapping fields (immunology, metabolism, artificial intelligence, drug discovery, structural biology), to build fresh ideas and collaborations for the next chapter of innate immune discovery and translation. Finally, this conference is being held concurrently with a Keystone Symposia meeting on Systems and Engineering Immunology, which will allow attendees to interact with colleagues in a related area of immunology.