Cold Spring Harbor Conference on Systems Immunology Cold Spring Harbor, NY March 13 – 16, 2019 ABSTRACT Immune responses are orchestrated by diverse cells and molecules operating over space and time and across different scales, for example, complex repertoires of lymphocyte receptors can discriminate between self and non-self molecular determinants and subsequently trigger dynamic cell-cell interactions culminating in the production of effector functions including antibody production and killer T cell proliferation. 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 a systems-level integration of high-dimensional and quantitative approaches, and computational modeling efforts to dissect systems level behavior that is challenging to intuit. It is clear that effective collaborations between experimental immunologists and computational and systems biologists will be required to advance our systems-level understanding of immune responses. Thus, we propose to host a meeting to enable a free cross-disciplinary exchange of existing ideas and expertise in the emerging field of systems immunology. It is hoped that this meeting will provide a mechanism to establish new collaborations, and a forum for discussing new experimental and computational approaches. The proposed meeting will focus on recent advances at the interface of immunology and systems 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 meeting will nucleate 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 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 people to attend, the vast majority of whom will be presenting a poster or talk. The participation of young investigators, minority, and women scientists is strongly encouraged. This proposal includes requested funding to support the participation of early career investigators in this important meeting.

Cold Spring Harbor Conference on Systems Immunology Cold Spring Harbor, NY March 13 – 16, 2019 PROJECT NARRATIVE The immune system is a complex network of interactions among cells that sense and respond to pathogenic infections and other assaults, and decades of research have produced a robust understanding of its basic structure and function. However, how different pieces of the system work together to generate immune response behavior is not well understood. Now new quantitative, high-throughput experimental approaches are enabling the interrogation of immune cells and other components on a global scale. These technological advances have the potential to deepen our understanding of immune responses and eventually lead to new therapeutic strategies aimed at harnessing patients' own immune systems to treat diseases. Achieving this potential will require methods and conceptual advances from other scientific disciplines, including computer science and systems biology. This international conference will bring together the leading experts in immunology and systems biology and provide 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.