Mucosal Immunology Studies Team (MIST) (U01 Clinical Trial Not Allowed)

Mucosal Immunology Studies Team (MIST) (U01 Clinical Trial Not Allowed) is sponsored by National Institutes of Health. Solicits applications for a cooperative research group focusing on immune mechanisms and regulation at mucosal surfaces of the respiratory, gastrointestinal, and urogenital tracts.

Expired RFA-AI-25-018: Mucosal Immunology Studies Team (MIST) (U01 Clinical Trial Not Allowed) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Allergy and Infectious Diseases ( NIAID ) Funding Opportunity Title Mucosal Immunology Studies Team (MIST) (U01 Clinical Trial Not Allowed) U01 Research Project – Cooperative Agreements April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 .

August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Part 2, Section III.

3. Additional Information on Eligibility. Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to solicit applications from eligible organizations to participate in a cooperative research group, the Mucosal Immunology Studies Team (MIST), focusing on immune mechanisms and immune regulation at mucosal surfaces of the respiratory, gastrointestinal, and urogenital tracts.

The main objective of this program is to break new ground in the understanding of basic mucosal immune mechanisms by introducing new ideas, approaches, and technologies that address difficult questions in mucosal immunology.

Funding Opportunity Goal(s) To assist public and private nonprofit institutions and individuals to establish, expand and improve biomedical research and research training in infectious diseases and related areas; to conduct developmental research, to produce and test research materials.

To assist public, private and commercial institutions to conduct developmental research, to produce and test research materials, to provide research services as required by the agency for programs in infectious diseases, and controlling disease caused by infectious or parasitic agents, allergic and immunologic diseases and related areas.

Projects range from studies of microbial physiology and antigenic structure to collaborative trials of experimental drugs and vaccines, mechanisms of resistance to antibiotics as well as research dealing with epidemiological observations in hospitalized patients or community populations and progress in allergic and immunologic diseases. Because of this dual focus, the program encompasses both basic research and clinical research.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV.

Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII.

Agency Contacts Section VIII. Other Information Part 2. Full Text of Announcement Section I.

Notice of Funding Opportunity Description The purpose of this notice of funding opportunity (NOFO) is to solicit applications from eligible organizations to participate in a cooperative research group, the Mucosal Immunology Studies Team (MIST).

The objectives of MIST are to discover and define novel basic immune mechanisms, cells, mediators, and pathways that provide a more complete understanding of mucosal immune mechanisms; to explore innovative hypotheses; and to address difficult unsolved questions in mucosal immunity.

The eventual goal is to gain insight into how the mucosal immune system responds to microbial factors at barrier surfaces, maintains homeostasis, and communicates systemically in health and disease. Studies may use relevant animal models or human tissues to achieve this goal. This program is not intended to support development and/or evaluation of mucosal vaccines or therapies, or research primarily focused on pathogens.

The mucosal immune system satisfies a range of diverse requirements from maintaining a limited microbial burden in the lungs and upper reproductive tract to coexisting with many trillions of microbes in the large intestine. An imbalanced mucosal immune response to food, allergens, microbial flora, or pathogens can lead to tissue damage or chronic inflammation. Therefore, responses at the mucosa require tight regulatory control.

Recent discoveries have established that the mucosal immune system connects to other body systems in addition to the systemic immune system. In particular, cross-talk between gut microbiota and the mucosal immune system has been shown to influence multiple aspects of human health and disease that, in addition to immune-mediated diseases, includes obesity, nervous system/mental health disorders, and hepatic and cardiovascular diseases.

Still, much remains unknown in these areas. With the goal of promoting a collaborative program to encourage basic and translational research focused on immunity at mucosal surfaces, the Mucosal Immunology Studies Team (MIST) was initiated in 2011 ( RFA-AI-10-008) , renewed in 2016 (RFA-AI-15-023 ) and again in 2021 ( RFA-AI-20-027 ).

The program has supported 28 U01 awards, two cores (imaging, animal models), and 56 pilot projects including early career awards, innovative collaborations, and translational projects. Research Objectives and Scope This NOFO will support research to define fundamental aspects of immunity at mucosal surfaces.

This NOFO intends to stimulate new basic and applied research that will contribute toward understanding broadly applicable mechanisms of mucosal immunology. Areas of interest and research studies responsive to this NOFO include, but are not limited to, those listed below.

Many of the following areas of investigation are not new, but advances in recent years suggest that these areas have matured to a level where directed research efforts can have an impact. These and other research areas may be addressed in this NOFO in the context of defining new mechanisms relevant to immune responses at the mucosa.

If infectious organisms, vaccines, adjuvants and/or mucosal diseases are used for the proposed studies, they must be employed as model agents and/or diseases to probe host mucosal immune responses to discover new information about mechanisms of immunity. Studies may use relevant animal models or human tissues to achieve this goal. Mucosal Epithelium: Barrier, Defense, Antigen Sampling, Immune Response Orchestration.

Mucosal surfaces are lined by tightly joined epithelial cells, which form a physical barrier between the body and the microbial flora, thereby serving as a first line of immune defense against microbial invasion. Mucosal epithelial cells secrete a wide array of substances such as mucins, anti-microbial peptides, surfactant proteins, lipids, lysozyme, and nitric oxide, which non-specifically shield the mucosa from microbial damage.

Mucosal epithelial cells are capable of innate recognition of microbial motifs via cell surface or cytosolic molecules, such as toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) molecules, and retinoic acid-inducible gene (RIG-I) like molecules, which trigger the production of cytokines and chemokines that activate and mobilize immune cells.

Specialized epithelium and epithelial cells (e.g., M cells, Paneth cells, goblet cells, tuft cells, follicle-associated epithelium) further contribute to immune responses by antigen/chemical recognition, transport of antigens across the mucosa, and presentation of antigens to dendritic cells (DC) or other immune cells within the mucosa.

These mucosal epithelial cell types and their mediators serve to provide protection from pathogens, shape the microbiota, and influence host immune responses. How epithelial cells interact with and respond to luminal molecules and microbes is critical to orchestrating the balance of effector and regulatory responses needed to respond appropriately to pathogens.

In addition, epithelial cells must maintain tolerance to innocuous antigens in air, food, and the microbial flora. The mechanisms, cells, and pathways governing epithelial barrier integrity, antigen recognition and acquisition, and presentation to DCs and immune cells to induce protection, ignorance or tolerance are important areas for further study.

Examples of potential research studies in this area include, but are not limited to: Signals that drive antigen-sampling epithelial cells at respiratory and other mucosal sites to become M cells Molecular pathways involved in apical-to-basolateral translocation of luminal antigens Regulation of goblet cell sentinel and antigen capture functions at diverse mucosal sites Mechanism of sensing pathogens or allergens by chemosensory tuft cells in the airway Relative contribution of specialized mucosal epithelial cells to mucosal surveillance, immunity, and tolerance Epithelial factors influencing dendritic cell or T cell recruitment and differentiation Functional consequences of MHC Class II expression on epithelial cells of the lung and intestine Tissue-specific sites of presentation of antigens taken up in the lung, intestine, or urogenital tract; and influence of local conditions on resultant responses Role of mucus in attenuating microbial virulence and in shaping immune responses Mucosal Immunoglobulin and Mucosal B Cell Responses.

IgA isotype antibodies predominate at the mucosal surface and are considered a first line of defense against microbial invasion through the mucosa. Particularly important functions of these antibodies are protection against infections and establishment of a healthy microbiota.

Despite discoveries that have provided a framework for understanding induction of IgA-producing B cells and transport of IgA, much remains unknown, for example, where and how B cells meet antigen, what factors influence the site of IgA production in the gut, where long-term memory is established, and how responses to infection and commensal microbes differ at various mucosal sites.

To facilitate mucosal vaccine development, more information is needed to 1) understand where and how local IgA is produced and 2) identify the precise role of IgA and other mucosal immunoglobulins in protecting against infectious pathogens and maintaining a balance with commensal microbes.

Examples of research studies in this area include, but are not limited to: Strategies to induce IgA at stratified epithelial mucosa, such as the lower female reproductive tract Contribution of Peyer’s Patch CD4 T cell subsets to IgA B cell differentiation Origin of T follicular helper T cells (Tfh) at mucosal locations Role of FoxP3+ regulatory T cells (Tregs) and follicular regulator cells (Tfr) in production of affinity-matured gut IgA antibodies Epithelial, stromal, and dendritic cell mechanisms involved in development of IgA-producing B cells Mucosal Immunity and Inflammation.

The mucosal immune system is challenged to respond to harmful organisms while regulating the resultant influx of immune cells to prevent tissue injury due to inflammation. In the gut, several lines of evidence support the idea that the commensal flora exert an anti-inflammatory influence on the mucosa.

Alterations in microbial flora may lead to inappropriate responses in which commensal microbes serve as surrogate pathogens and thus stimulate a chronic inflammatory response. In the relatively less colonized surfaces of the respiratory tract, failure to tightly control immune responses to pathogens or commensal microbiota can also lead to chronic inflammation and tissue destruction.

To limit inflammatory responses, the airways, gut, and other mucosal surfaces employ a range of complex physical, innate, and adaptive immune defenses. Alterations of any of these defenses could promote an uncontrolled inflammatory response that may lead to tissue injury, and also may promote pathology at distant non-mucosal sites, such as the central nervous system or the cardiovascular system.

Complex mucosal systems to prevent responses to harmless antigens and limit inflammatory responses to pathogens are not well understood and represent an important area for further study.

Examples of research studies in this area include, but are not limited to: Mucosal immune mechanisms in pathogen and disease tolerance that limit tissue destruction or inflammation Influence of circadian rhythms on immune cell/pathway functions in homeostasis, protective immunity, and inflammation Mechanism and effects of immune scarring at the mucosa that lead to lasting mucosal changes evident long after or in the absence of pathogen infections (e.g., urothelial cell changes influencing recurrent bladder infection, recurrent enteric infections leading to an inflammatory bowel disease (IBD)-like syndrome, airway remodeling in airway disease) Mechanisms of lung-gut cross-talk that affect mucosal immunity and mucosal inflammation Role of trained innate immunity in mucosal infection and chronic inflammation Identification and mechanisms of action of dietary factors, microbes, and microbial metabolites that influence mucosal immunity and inflammation Role of innate lymphoid cells, Mucosal-associated invariant T (MAIT) cells, gamma delta T cells, resident T memory cells, and regulatory T cells in mucosal protection, inflammation, and tolerance Defining correlates of mucosal protection or tolerance and predictors of inflammatory outcome in humans Mechanisms by which mucosal responses differ between microbial infection of the upper vs. lower airways Mucosal Immune System Cross-Talk with the Nervous System.

Numerous connections among the microbiota, mucosal immune system, and nervous system have been identified, suggesting an interplay among the nervous and mucosal immune systems in detection and response to microbes and other molecules at mucosal surfaces. Tissues that are directly exposed to the external microbial flora such as mucosal surfaces of the digestive, lung, and urogenital tracts play a central role in immune surveillance.

These sites are densely innervated by nervous system sensory cells, which recent pioneering studies have found to be important in regulating 1) mucosal immune cells, 2) their responses, and 3) barrier integrity.

Effective communication between the mucosal immune and nervous systems shapes homeostasis of the GI and respiratory systems, can allow for more integrated detection and response to environmental insults and infectious agents, and may fine-tune responses to pathogens and tissue damage.

Understanding how neuro-immune interactions shape responses to microbes, allergens, and other environmental stimuli is critical for identification of novel targets for development of future therapeutics for mucosal infections and inflammation, as well as disorders that may be initiated at mucosal surface, but manifest at non-mucosal sites such as the nervous system or cardiovascular system.

Examples of research studies in this area include, but are not limited to: Mechanisms by which the enteric and/or respiratory nervous systems and central nervous system integrate with microbe-induced mucosal immune responses Role of the nervous system in immune system development at mucosal sites Mechanisms of cross-talk between mucosal neurons and glial cells and mucosal immune cells, e.g., mast cells, macrophages, innate lymphoid cells (ILCs), lymphocytes, and mucosal epithelial cells Effects of the microbiota on the peripheral enteric nervous system and how this influences development of the mucosal immune system Immune consequences of ILC interactions with neurons at mucosal sites Nervous system involvement in restraining versus promoting immune responses Mucosal Immunity in Systemic Health and Disease.

Emerging paradigms suggest that mucosal immunity has wide-ranging impacts in human health and disease. As such, maintaining homeostasis at mucosal barrier surfaces is central to overall organismal health. These processes involve interactions between immune cells and diverse cell types and organ systems that are not traditionally associated with mucosal immunity.

In addition, immune responses that are primed and conditioned at mucosal barrier sites have inter-organ effects, subsequently impacting disease pathophysiology at tissue sites distal to the mucosa. Focus on these new emerging areas of mucosal immunology may push this field forward in the development of next generation mucosal immune-focused vaccines and immunotherapies.

Examples for research studies in the area include, but are not limited to: Interactions between the mucosal immune system and less studied cell types at mucosal barriers associated with the nervous system, stroma, endothelium, and endocrine system Interrogation of immune responses initiated and conditioned at mucosal barriers, including the intestine or airway, the inter-organ system consequences, and impact on pathophysiology of distal immune-mediated diseases such as psoriasis, arthritis, multiple sclerosis, neurodegeneration, and hepatitis Cross-disciplinary interactions between the mucosal immune system and organ systems including the gut, lung, liver, central nervous system, joints, skin, and kidneys Mucosal immunity shaping of the efficacy or adverse outcomes of specific therapies Modeling mucosal immune interactions with diverse cell types or inter-organ systems in human samples or in vitro systems The MIST program is intended to support studies that break new ground in the understanding of mucosal defense and mucosal immunoregulation.

Proposed studies may include a range of mucosal probes to gain new insights into mucosal immune defense mechanisms, such as microbes, pathogens, vaccines, adjuvants, infections, and mucosal inflammation.

Applications that propose to conduct research in the following areas will be considered non-responsive and will not be reviewed: Clinical trials ; however, the use of samples obtained from human subjects in clinical trials funded through other mechanisms is allowed. Studies involving HIV, AIDS, SIV. Studies focused solely on skin or epidermis without a connection to mucosal immune function.

Studies focused primarily on specific microbes, infections, vaccines, or adjuvants that do not use these agents as probes to gain new insights about mucosal immune mechanisms. Studies focused on non-immune mechanisms of pathogenesis, such as non-immune factors involved in impaired tight junction integrity and increased intestinal permeability; genetics linked to non-immune related epithelial barrier dysfunction.

Projects focused on autoimmune or inflammatory diseases (e.g., inflammatory bowel disease, celiac disease, cystic fibrosis, etc.), lung or intestinal transplantation, or asthma/allergy that do not use these diseases as probes to gain new insights about mucosal immune mechanisms. Investigations that do not focus on the study of mucosal immune or immunoregulatory mechanisms, mucosal cells, mucosal molecules or mucosal pathways.

Steering Committee. A Steering Committee will be established to direct the overall efforts of the MIST program. The Steering Committee will be composed at a minimum of the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) of each of the awards and an NIH Project Scientist.

The Steering Committee will develop a "MIST Plan" that will articulate the goals of the MIST Program and will be used as a reference for making recommendations regarding use of the Infrastructure and Opportunities Fund (IOF). The Steering Committee will be responsible for organizing an annual competition for high priority research projects aligned with the MIST research goals that could be funded through the IOF.

The oversight of these activities will facilitate and enhance cooperative and collaborative efforts, among both MIST members and the research community at large, that are best suited to achieve the goals of the program and to advance understanding of immune mechanisms at the mucosa. Infrastructure and Opportunities Fund (IOF).

To capitalize on emerging opportunities and sharing of resources and expertise consistent with the goals of MIST, an IOF will be made available.

Examples of activities supported by the current IOF include development and management of a website for MIST activities; collaborative and pilot and/or feasibility projects among MIST members; translational projects; early-stage investigator projects; and imaging and animal model development cores. IOF projects must be within the scope of this NOFO and may be submitted by all MIST members. IOF Management.

One institution will be chosen by NIH after award from the successful applicants to manage the IOF for the entire MIST. This institution must agree to take responsibility for managing the IOF, including establishing an administrative structure for disbursement and tracking funds, and under the advice of the Steering Committee, establishing procedures for reporting status of IOF projects to NIH and the Steering Committee.

See Section VIII. Other Information for award authorities and regulations. Section II.

Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.

2 for additional information about the substantial involvement for this NOFO. Application Types Allowed Renewal - Renewal to RFA-AI-20-027 The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Not Allowed: Only accepting applications that do not propose clinical trials. Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards NIAID intends to commit $3,000,000 in FY 2026 to fund 4-5 awards, which includes $750,000 total costs for an Infrastructure and Opportunities Fund (IOF).

Application budgets are not expected to exceed $350,000 direct costs per year, excluding the IOF budget. The proposed budget must reflect the actual needs of the proposed project. The scope of the proposed project should determine the project period.

The maximum project period is five years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions - Includes all types Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) Foreign Organizations/ International Collaborations NIH will no longer issue awards (new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts.

All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025. Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding.

This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components , funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors. Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Other Attachments: The following attachment is required for this NOFO and must be included as a separate pdf attachment. If absent, the application will be considered incomplete and will not be reviewed. Infrastructure and Opportunities Fund (IOF) Management Plan: The filename “IOF.

pdf” should be used and will be reflected in the final image bookmarking for easy access for reviewers. Applicants must include a plan (maximum of 3 pages) for administering the IOF to include coordination, communication, and management of the proposed IOF; proposed measures and procedures for disbursement, reporting and monitoring of expenditures; and plans for soliciting, evaluating, and selecting projects.

Applicants should NOT include or propose specific projects to be funded from the IOF; these decisions will be made in conjunction with the Steering Committee after award. SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: In the budget section, applicants should include funds for travel to the Rockville, Maryland area for two Steering Committee meetings within the first 12 months, and usually once annually thereafter, for the PD(s)/PI(s).

For multi-PD/PI applications, the budget should include travel funds sufficient for all PD(s)/PI(s) to attend the Steering Committee meetings. All applicants must propose an IOF Budget. One (1) IOF budget of up to $750,000 total costs will be awarded to one recipient organization, which will be selected by NIAID post-award to manage the fund.

Each applicant should propose Direct Costs as a single line item in the Other Direct Costs Category of the Budget. Direct Costs proposed for the overall administration and oversight of the IOF may be requested and must comply with NIH Grants Policy. Direct Costs for the research projects using IOF funds should be estimated at 4-8 pilot projects per year.

F&A costs will be applied in accordance with NIH Grants Policy. All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Specific Aims: List the broad, long-range objectives and goals of the proposed project and describe the work to be completed.

Research Strategy: Within the research strategy, applicants must include the following: A clear and detailed description of how the proposed studies contribute knowledge critical to achieving the goal of advancing understanding of mucosal immune mechanisms or addressing difficult unsolved questions in mucosal immunity.

A clear and detailed description of how the proposed studies explore hypotheses related to immunity at mucosal surfaces and/or identify or define basic mucosal immune mechanisms, cells, mediators, and pathways. If approaches including infectious organisms, vaccines, adjuvants and/or mucosal diseases are proposed, describe how these model agents and/or