SUMMARY: SPARED CENTER The Silvio O. Conte Center for Stress Peptide Advanced Research, Education, & Dissemination (SPARED) at McLean Hospital will combine world-renowned preclinical and clinical researchers in the field of stress biology to comprehensively examine, compare, and contrast the neurobiological effects of CRF (Corticotropin-Releasing Factor) and PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide), two peptides with well-validated roles in the biology of stress-related conditions. Genetic alterations in these systems render people more vulnerable to stress, administration of either peptide mimics key stress effects, and both systems are altered by stress. Their high degree of conservation across species suggests that each regulates equally important—yet subtly different—aspects of stress responsiveness. Indeed, a major difference revealed by animal models is that the stressful effects of PACAP system activation tend to be more persistent than those of CRF system activation. The scientific elements include complementary molecular, cellular, circuit, physiologic, and behavioral measures in mice and humans, as well as detailed hypothesis testing in postmortem brain samples obtained from individuals with Post-Traumatic Stress Disorder (PTSD) and healthy controls. To complement the science, the Center will also support a broad range of training and educational activities, including expansion of outreach programs as well as social media approaches to engage scientists and lay-persons. Our overall Aims provide the basis for synergy that will transform this work from a collection of individual projects into a cohesive Center where each element enriches, and is enriched by, the activities of the others, serving as a resource that benefits the scientific community and beyond. Aim 1 (Collaboration) is to bring together leading researchers who are committed to understanding stress and reducing its health burdens by combining new insights on biology with cutting-edge technologies, and establish a framework that enables sustained collaboration in the service of advancing discovery and innovation. Aim 2 (Investigation) is to use a multidisciplinary, RDoC-compatible approach to conduct high-impact research that transforms our mechanistic understanding of CRF and PACAP systems to facilitate the development of improved diagnostics and therapeutics for a range of DSM-defined disorders that are caused or exacerbated by stress. Aim 3 (Outreach) is to implement unique and impactful approaches that enhance education, training, and career development for future generations of translationally- oriented stress researchers. Aim 4 (Innovation) is to use information and internet technologies to transform collaboration, investigation, and outreach to achieve broad communication of Center-related activities, including sharing of educational materials and strategies, nimbly disseminating news, and making available data sets. Pursuit of these goals will establ...