September 2018 DAIT Council-Approved Concepts

Concepts represent early planning stages for program announcements, requests for applications, or solicitations for Council's input. If NIAID publishes an initiative from one of these concepts, we link to it below. To find initiatives, go to Opportunities & Announcements.

NB: Council approval does not guarantee that a concept will become an initiative.

Table of Contents

Fc-Dependent Mechanisms of Antibody-Mediated Killing

For the published program announcement, see the October 5, 2018 Guide announcement, Fc-Dependent Mechanisms of Antibody-Mediated Killing (R21 Clinical Trial Not Allowed). For the published request for applications, see the October 5, 2018 Guide announcement, Fc-Dependent Mechanisms of Antibody-Mediated Killing (U01 Clinical Trial Not Allowed).

Processing and Presentation of Non-Conventional MHC Ligands

Program Announcement (R01)—proposed FY 2020 initiative

Contact: Timothy Gondré-Lewis

Objective: The objective of this program announcement is to understand the antigen processing and presentation mechanisms used in generating novel peptide products and the contribution of these unique antigenic products to protective immune responses against infectious pathogens, in response to vaccines, or in the induction or progression of immune-mediated diseases.

Description: This initiative will support exploratory/developmental studies that define novel antigen processing and presentation mechanisms used to generate “non-classical and unconventional” T cell epitopes involved in protective immunity against infections or triggered by vaccines, or that contribute to the development and progression of immune-mediated diseases. Proposed studies may include but are not limited to: studies of peptide ligands derived from translation initiated at codons other than the traditional methionine codons and peptide ligands derived from non-contiguous sequences; hybrid peptides, neoantigen ligands derived from post-translational modifications, and ligands presented by non-classical major histocompatibility complex (MHC) molecules (HLA-E, F, and G) and non-conventional molecules (e.g., CD1 family, MR1, TL); and novel technologies to identify non-classical, non-conventional antigen presenting molecules and corresponding T cell receptor (TCR) usage.

Applicants with preliminary data, established models, and/or planning longer-term studies may wish to apply using the R01 mechanism.

Program Announcement (R21)—proposed FY 2020 initiative

Contact: Timothy Gondré-Lewis

Objective: The objective of this program announcement is to understand the antigen processing and presentation mechanisms used in the generation of novel peptide products and the contribution of these unique antigenic products to protective immune responses against infectious pathogens, in response to vaccines, or in the induction or progression of immune-mediated diseases.

Description: This initiative will support exploratory/developmental studies that define novel antigen processing and presentation mechanisms used to generate “non-classical and unconventional” T cell epitopes involved in protective immunity against infections or triggered by vaccines, or that contribute to the development and progression of immune-mediated diseases. Proposed studies may include but are not limited to: studies of peptide ligands derived from translation initiated at codons other than the traditional methionine codons and peptide ligands derived from non-contiguous sequences; hybrid peptides, neoantigen ligands derived from post-translational modifications, and ligands presented by non-classical MHC molecules (HLA-E, F, and G) and non-conventional molecules (e.g., CD1 family, MR1, TL); and novel technologies to identify non-classical, non-conventional antigen presenting molecules and corresponding TCR usage.

Exploratory and novel studies for which preliminary data is limited but that break new ground or extend previous discoveries toward new directions or applications will be encouraged. Projects that are high-risk with potentially high-reward that may lead to novel discovery techniques or methods will also be encouraged.

Computational Models in Immunity

Request for Applications—proposed FY 2020 initiative

Contact: Joseph Breen

Objective: This program will support developing, refining, and validating computational models of the immune system through iterative immunological experimentation and computational modeling. It will also support pilot projects, summer schools, and symposia to make computational modeling more accessible to the broader research community.

Description: This renewal will build on progress gained through previous solicitations, as well as through independent progress made by the broader research community in the areas of computational and systems immunology. The FY 2020 initiative will include the following components:

Individual projects focused on developing or further refining computational models of immunity to infection or vaccination. Investigators will be encouraged to use existing datasets in ImmPort or other public databases for model refinement and validation, and they will be required to include novel immunologic experimentation to generate data for model validation and refinement.

Community outreach: Each awardee will be required to develop/execute activities that encourage the use of computational modeling by the immunology community. Such activities may include workshops, scientific symposia, mini-courses, or visiting scientist training opportunities focused on computational modeling of immunity.

FY 2020 Changes (compared to the FY 2015 program):

There is no requirement to use an NIAID Category A-C pathogen or emerging/re-emerging infectious disease as was required in the FY 2015 program. Any model pathogen may be used if it is part of NIAID’s mission. The program’s new name reflects this change. Each project is now planned as a single project U01 with integrated activities instead of the previous U19 format where the immunology and computation were in separate projects.

Molecular and Genetic Characterization of Inborn Errors of Immunity

Program Announcement With Special Receipt, Referral, and or Review Considerations—proposed FY 2020 initiative

Contact: Frosso Voulgaropoulou

Objective: The purpose of this initiative is to advance the experimental validation and functional characterization of genetic variants in candidate genes that result in primary immunodeficiency diseases, now referred to as inborn errors of immunity, and to elucidate the molecular, cellular, and immunological mechanisms of these disorders. Understanding the genetic basis of primary immunodeficiencies is essential for their diagnosis, prognosis, and developing precision therapeutics.

Description: This initiative will solicit R01 applications to support the biochemical, immunological, and functional characterization of genetic variants in candidate genes that cause inborn errors of immunity, identified through next generation sequencing (NGS). Computational analysis of genomic data is expected to be finalized by the time applications are submitted and compelling preliminary evidence should suggest causality between genetic variant(s) and disease phenotype.

Characterizing single nucleotide variants, de novo mutations, insertions or deletions (indels), or copy number variants in candidate genes are appropriate. Applications that aim to characterize digenic mutations or structural variations (large insertions or deletions, translocations, inversions, and copy-number variations) as causes of inborn errors of immunity are also welcome. Studies that propose using targeted gene sequencing panels, which analyze specific mutations known to cause primary immunodeficiency diseases, are not appropriate for this initiative since they will not aid in identifying novel disease-causing mutations. In addition, studies that aim to characterize somatic mutations are not appropriate.

Relevant cell types isolated from patients with primary immunodeficiencies and appropriate controls (e.g., affected or unaffected family members) are strongly encouraged for the delineation of the functional consequences of the mutations under investigation. If animal models are proposed, a clear correlation between human and animal disease phenotypes should be established. In all cases, preliminary data should demonstrate that the genotype/phenotype correlation recapitulates the patient’s clinical disease.

Development of Radiation/Nuclear Medical Countermeasures (MCMs)

Broad Agency Announcement—proposed FY 2020 initiative

Contact: Anuj Patel

Objective: This initiative will address gaps and accelerate the research and development of MCMs against acute and delayed radiation syndromes.

Description: This initiative will support the research and development of MCMs against acute and delayed radiation syndromes.

Informatics Methodology and Secondary Analyses To Explore Shared Immunology Study Data in ImmPort

Program Announcement With Special Receipt, Referral, and or Review Considerations—proposed FY 2020 initiative

Contact: Quan Chen

Objective: The objective of this initiative is to support the generation of innovative informatics tools and methodologies to validate research findings or generate new hypotheses that augment the usefulness and impact of ImmPort data.

Description: This initiative will solicit applications for innovative informatics tool and methods development to maximize the value of ImmPort data by funding continued effort in the following areas:

1. Developing bioinformatics tools or methods that use data in ImmPort for secondary analyses to generate hypotheses

2. Developing bioinformatics tools or methods that use data in ImmPort to validate research outcomes

3. Developing bioinformatics tools or methods that facilitate new ways to access or reuse data in ImmPort (e.g., reference datasets, cross-study analyses, standardization or integration)

Content last reviewed on October 5, 2018