April 14, 2023
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Eye Institute (NEI)
National Institute on Aging (NIA)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Environmental Health Sciences (NIEHS)
National Center for Complementary and Integrative Health (NCCIH) as per NOT-AT-24-007
All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers. The following NIH Offices may co-fund applications assigned to those Institutes/Centers.
Office of Research on Women's Health (ORWH)
This Notice of Special Interest (NOSI) invites applications for exploratory, early, and conceptual stage research projects aimed at the design, development, and implementation of a future national, interdisciplinary, collaborative, team science research network that will advance the study of the exposome in autoimmune diseases (Exposome in Autoimmune Diseases Collaborating Teams, EXACT). The future EXACT Network will conduct research to discover the environmental exposures that influence disease susceptibility, onset, and outcomes and will develop a systems- level approach to understanding the mechanisms underlying how exposures perturb cellular, organ, and tissue function across autoimmune diseases (AID). The exploratory, developmental grants requested under this NOSI are intended to enable institutions to plan research strategies and develop partnerships, infrastructure, and capabilities needed to address the major goals of a future collaborative EXACT network and to develop a research framework and strategies to support coordination among studies, collaborative research projects, and sites.
This Notice is a collaborative effort between ORWH, NIAMS, NIEHS and NIH Institutes, Centers, and Offices engaged in AID research. The research focus addresses one of the key gap areas identified by the National Academies of Science, Engineering and Medicine Report: Enhancing NIH Research on Autoimmune Disease (2022) (NASEM Report) (Enhancing NIH Research on Autoimmune Disease |The National Academies Press). The objectives reflect the NASEM Report's emphasis on planning, collaboration, and innovation and address the Consolidated Appropriations Act, 2023, ( Public Law 117-328 ) directives to the NIH Office of the Director, Office of Research in Women’s Health, to enhance coordination and collaboration regarding autoimmune disease research activities across Institutes and Centers.
The exploratory and developmental grant will not be a prerequisite for submission of any future application.
Recent advances in environmental health research highlight the potential role of the exposome, defined as the measure of all the exposures of an individual lifetime and how those exposures relate to an individual’s health, on disease susceptibility onset and severity. Human diseases often result from complex interactions between patients’ genetic susceptibilities and environmental exposures (exposome). Women and in particular women of understudied, underrepresented, and underreported populations are disproportionately affected by autoimmune disease, suggesting increased exposure to environmental factors as one of the mechanisms for the increasing prevalence of AID. Exposures can be internal or external, ranging from diet, microbiome, alcohol, addictive drugs, medications, and exogenous hormones to air pollutants, cigarette smoke, chemicals and heavy metals, UV radiation, and other factors related to geographic location and changing climatic conditions. Exogenous (e.g., pollutants) and endogenous (e.g., inflammation) exposures might be influential during early life while the immune system is still developing. As psychosocial stressors often co-occur with other environmental factors, these factors may disproportionately impact groups such as children, pregnant persons, and lower socioeconomic status groups who are also disproportionally affected by AID.
Few environmental exposures and gene interactions have been systematically examined in AID, and the role of the exposures and the biological responses that they generate in disease initiation and progression remain largely unknown. Significant research gaps include elucidation of how the exposome affects the heterogenous molecular and cellular pathways leading to autoimmunity and novel approaches to avoid or neutralize interactions that might contribute to AID. Recent technological advances to measure individual exposure and the ability to integrate high-dimensional analytics such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and adductomics, with the help of artificial intelligence and machine learning, can be utilized now to examine how specific exposures govern biological responses in patients with AID. In addition, sensing wearables linked to reliable monitoring and mobile devices using wireless technology are available to measure exposures such as air pollutants and chemicals. Approaches to collect exposure data from patients as they move about their daily lives with such wearable devices and monitor diet and their microbiomes are already validated.
The future EXACT initiative is envisioned as a multisite, collaborative network that will adopt a team science approach to produce a systems level understanding of the role of the exposome in AID. The research framework of the future EXACT Network is anticipated to be broad and interdisciplinary and may include 1) collaborative projects addressing how specific exposures impact AID etiology and progression and 2) pilot studies to validate additional exposure sensing and monitoring devices for complex exposures such as exercise and sleep. Collaborative projects will be carried out by disease teams and technology and analytic cores working under an administrative core. Disease teams will collect clinical, phenotypic, and exposure data (cross-sectional and longitudinal cohorts), whereas technology and analytic cores will conduct high dimensional analysis of tested patients. Pilot studies will develop and validate sensing and monitoring devices for complex exposures for AID patients. The entire network will be supported by a robust data science core that will integrate and conduct system-level data analysis.
Collaborations with successful programs such as the All of Us, Accelerated Medicine Partnership® Autoimmune and Immune Mediated Diseases, and Environmental Influences in Child Health Outcomes (ECHO) programs will be encouraged. Existing NIEHS facilities and resources to measure exposures could be leveraged to improve efficiencies and standardization.
The goal of this NOSI is to support research and activities that will 1) conceptualize and begin testing, novel, cutting-edge technologies combined with data science to the study of exposome in AID; 2) explore strategies to address the multidomain, multilevel approach needed to comprehensively measure the exposome and assess constructs to evaluate their effect on disease pathways; and 3) develop collaborations and partnerships to leverage existing cohorts and other resources needed to map the role of the exposome across AID and the lifespan.It is expected that any awards funded through this program will interact with, contribute to, and leverage the products of any programs established as part of the NIH efforts to establish an Exposome Coordinating Center and Community of Practice as outlined in the recently approved NIEHS Concept (https://www.niehs.nih.gov/about/boards/naehsc/agenda/feb2023/global_exposome_research_coordination_to_accelerate_precision_environmental_health_concept_508.pdf).
Areas of interest include but are not limited to:
Given the complexity of mapping the associations of the exposome with multiple autoimmune disorders, research teams will not only need to identify important research priorities but also require complementary skills, expertise, and resources to effectively address the challenge. The exploratory, developmental grants provided through this NOSI can be used to support team formation activities that create opportunities for the development of partnerships between researchers, institutions, community groups, and patients and transdisciplinary research strategies that represent diverse perspectives and scientific capacity. Applicants are encouraged to include two or more AID.
The activities may include (not all inclusive):
Application and Submission Information
This notice applies to the due date of June 16, 2023.
Submit applications for this initiative using one of the following notice of funding opportunity (NOFO) or any reissues of this announcement through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.
Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:
Investigators are strongly encouraged to contact the Scientific/Research Contact before preparing an application. All questions related to this NOSI can be addressed to NIAMS_EXACTPLAN@nih.gov.