Cold Spring Harbor Conference on Systems Immunology Cold Spring Harbor, NY April 18 – 22, 2023 ABSTRACT Immune responses are orchestrated by diverse cells and molecules operating over space and time and across different scales, for example, extremely complex repertoires of lymphocyte receptors can discriminate between self and non-self antigens and subsequently trigger dynamic cell-cell interactions culminating in the production of effector functions including antibodies and killing of virus infected cells. Critical discoveries have been made by experimental immunologists studying individual molecules, cells, and their interactions. Due to the complexity of the interactions among these diverse immune components, many fundamental issues associated with immune regulation and response orchestration remain unresolved. Further progress requires an integration of high-dimensional multi-omic approaches, and computational and quantitative modeling to analyze cellular behaviors at various scales of the system. These properties cannot be analyzed or intuited by conventional experiments. It is clear that effective collaborations between experimental immunologists and computational and systems biologists are required to advance our systems-level understanding of immune responses. This meeting is the third in a biennial series that catalyzing a cross-disciplinary exchange of new ideas and technologies in the rapidly evolving and expanding field of systems immunology. Building on the successes of the first two meetings held at CSHL in 2019 and 2021, have established this recurring meeting as the leading forum that can sustain a highly interactive community of Systems Immunologists. The proposed meeting will focus on recent advances at the interface of immunology and systems and computational biology, including rational design and applications of engineered immune particles and cells. Sessions will highlight multi-dimensional experimental platforms and computational approaches that are being used to analyze signaling and genomic states of individual immune cells that control discrete effector responses in a spatiotemporal manner. Integration of immunogenic, tolerogenic or pathophysiologic responses at different levels of scale – cellular, tissues and organs in mice and humans will be explored. Shared and unique design principles that underlie the development, functioning and evolution of the immune system will be discussed from an analytic standpoint. The session on Human Systems Immunology will include high-dimensional analyses of immune responses to SARS-CoV-2 infection as well as to COVID-19 vaccines. The meeting will nurture and foster a community of systems immunologists that are coupling high-dimensional profiling and imaging with computational and quantitative analyses to deepen the understanding of immune system states and responses. Oral presentations will be given by a group of distinguished invited speakers as well as speakers selected from submitted abstracts. Selected speakers will include primarily graduate students, postdoctoral fellows and junior faculty aiming for maximal inclusion of young investigators. Of special importance are the two poster sessions, where many participants can present their work in an atmosphere conducive to informal discussion. The meeting will be of moderate size and we expect about 250-300 people to participate in person, the majority of whom will be presenting a poster or talk, with an additional virtual audience of 150-200 layered over to provide broadened access to those who would otherwise be unable to participate. Presenters will be expected to attend in-person with exemptions granted on a case-by-case basis. The hybrid format will allow broadened access to scientists who would otherwise be unable to attend because of travel/visa restrictions, family obligations or financial burden. The participation of young investigators, minority, and women scientists will be strongly encouraged. This proposal includes requested funding to support the participation of early career Investigators.

Cold Spring Harbor Conference on Systems Immunology Cold Spring Harbor, NY April 18 – 22, 2023 PROJECT NARRATIVE The immune system comprises of diverse types of cells that manifest complex dynamical interactions while sensing and responding to pathogenic infections as well as tissue stress and injury. Decades of experimental research have produced a robust understanding of its basic structure and function. However, how different pieces of the system work together to generate coherent yet distinctive immune responses are not well understood. To address this challenge, an interdisciplinary community of experimental immunologists and computational and systems biologists have nucleated the emerging field of systems immunology. Rapidly evolving high- throughput experimental approaches coupled with computational and mathematical modeling are enabling the analysis of immune cell behaviors and their coordinated responses at unprecedented scales and resolution. These technological and computational advances have the potential to deepen our understanding of immune responses and eventually lead to new therapeutic strategies aimed at harnessing or modulating patients' own immune systems to treat diseases. Systems immunologists recognize that achieving this potential will require methods and conceptual advances from other scientific disciplines, including computer science, systems and synthetic biology. This biennial international conference brings together leading experts in immunology and systems biology and provides a forum for these scientists to share their latest discoveries. The application specifically seeks support for the active participation of early career investigators and trainees at this conference.