Notice of Special Interest (NOSI): EXposome in Autoimmune Disease Collaborating Teams PLANning Awards (EXACT-PLAN) (Clinical Trials Not Allowed)
Notice Number:

Key Dates

Release Date:

April 14, 2023

First Available Due Date:
June 16, 2023
Expiration Date:
June 17, 2023

Related Announcements

  • May 7, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195.
  • May 1, 2023 - Notice of NCCIH Participation in “Notice of Special Interest (NOSI): EXposome in Autoimmune Disease Collaborating Teams PLANning Awards (EXACT-PLAN) (Clinical Trials Not Allowed)”. See Notice NOT-AT-24-007.

Issued by

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.

Background and Goals

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.

Research Objectives

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 ( 

 Areas of interest include but are not limited to:

  • What characteristics (type, duration, geographical/socioeconomic differences) of environmental exposures potentially associated with development and progression of AID need to be examined?
  • What are the current technologies, methods, and services available and required to achieve the comprehensive identification and characterization of major contributors to the exposome?
  • What are the emerging technologies to analyze how the exposome may affect biologic functions of genetic variants associated with autoimmunity?
  • What are the best approaches to identify the biological pathways through which exposures contribute to autoimmune disease susceptibility, onset, response to treatment, progression, or flare?
  • What are the best and emerging strategies for the systemic characterizations of the diet and other environmental exposures interacting with the microbiome and for establishing relationships between the environment, the microbiome and autoimmune disease?
  • What emerging technologies can analyze how the exposome may affect biologic functions of genetic variants associated with autoimmunity?
  • What tools are needed to examine the shared and unique molecular pathways resulting from gene–environment interactions within and across AID?
  • How can artificial intelligence, machine learning and other computational approaches, and other technological approaches be tailored to support the study of the exposome in autoimmunity?
  • How can existing resources such as the Human Health Exposure Analysis Resource (, it’s associated data center ( and the ontology they have established (, the Comparative Toxicogenomics Database ( or the EPA CompTox Dashboard (, as well as others be leveraged to support data analysis and integration for the exposome in AID? What are the resources including cohorts, biospecimens, data, and devices needed or available to study the impact of the exposome on:
    • autoimmune disease in early life?
    • distinct and interacting biological and biopsychosocial factors contributing to observed and/or differences in AID, including the effect of puberty, menopause, and pregnancy?
    • pregnancy and postpartum outcomes in patients with AID?
  • How do non-chemical stressors such as psychosocial factors and social determinants of health, including gender, interact with the exposome to influence disease prevalence and severity among different populations?
  • How do key exposures across different domains (i.e., biological, behavioral, physical/built, sociocultural, healthcare system) and levels (i.e., individual, family, community, society) that comprise the environmental exposome singly or cumulatively impact AID across the lifetime?


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):

  • Establish a new collaboration.
  • Conduct small workshops to develop or expand existing research collaborations.
  • Establish an interdisciplinary research team, including identification and support of collaborators.
  • Plan activities for a new project involving a team of researchers and more than one autoimmune disease.
  • Conduct a landscape analysis of relevant existing resources, databases, registries, repositories, programs, and consortia.
  • Conduct secondary data analysis to support the hypothesis and research strategy of the future EXACT Network or its components.
  • The development and validation of new approaches, or adaptation and expansion of existing capabilities to measuring the exposome specifically in the context of AID:
    • Refine measures, assays, and outcomes to assess the exposure/biology and AID interface. Establish feasibility of a new approach/technology for data collection in exposome/AID research including the integration of environmental exposure with multi-omic biological responses.
    • Assess efforts to assure standardization of procedures across sites and among staff including the appropriateness of round-robin challenges and proficiency testing programs.
    • Establish quality assurance and quality control procedures (QA/QC) for data collection. Refine measures, assays, and outcomes to assess the exposure/biology and AID interface. Develop the research plan for the future EXACT Network or its components.
  • The exploration, development, and expansion of data science tools and methods, including analytical and data management efforts for integrating complex data within or across studies in support of the EXACT effort.
  • Develop tools needed for data sharing, harmonization and management and establish best practices.
  • Develop novel analytical techniques; sample size estimates with statistical justification; administrative procedures, including regulatory approvals if necessary; collaborative arrangements; duties and responsibilities of the study chairperson, sites, and other central resources; monitoring plans to assure patient protection and data integrity; and plans for addressing Federal gender/minority inclusion and human subjects protection requirements. 
  • Identify patient population cohorts; inclusion and exclusion criteria; adequate plans for recruitment and retention of participants; experimental design and protocols.
  • Implement resources to assure standardization of procedures across sites and among staff.
  • Develop tools needed for data collection and data management.
  • Develop plans for any training that is required to carry out the proposed study. This may include, for example, training of data collectors and individuals who will carry out the clinical assessments.
  • Engage stakeholders such as scientific or professional associations and patients and patient-advocates for better translation to inform the research agenda.
  • Develop a team science collaboration plan
  • Demonstration of clinical research readiness through study document preparation as applicable; IRB (and IACUC) approvals as applicable.
  • Finalization of memoranda of understanding (MOUs) or other agreements with partners for access to data; or to leverage and collaborate with existing networks and consortia.
  • Refinement and finalization of design, processes, organization, and coordination. 
  • Development of the statistical analysis plan and the data sharing and management plan, including plans for data harmonization within the future EXACT Network as well as coordination and data interoperability with other sites, consortia, or resources.

 Applications Not Responsive to this NOSI include

  • Projects without a primary focus on the exposome and AID
  • Projects that are not compliant with the NIH sex as a biological variable policy
  • Projects that do not include patient engagement or patient engagement plans
  • Projects that include a clinical trial

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.

  • PA-20-195 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

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:

  • For funding consideration, applicants must include “NOT-OD-23-112” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

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