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Reagents for Immunologic Analysis of Non-mammalian and Underrepresented Mammalian Models


Fast-Track proposals will be accepted. Direct-to-phase II proposals will be accepted. Number of anticipated awards: 3-5 Budget (total costs): Phase I: $300,000/year for up to 2 years; Phase II: $1,500,000 with appropriate justification by the applicant for up to 3 years. Background This Funding Opportunity Announcement (FOA) addresses the limited availability of reagents (e.g., antibodies, proteins, ligands) for the identification and discrimination of immune cells and the characterization of immune responses in specific non-mammalian models (arthropods, amphibians, fish (e.g., jawless, sharks, zebrafish), nematodes, marine echinoids) or in specific underrepresented mammalian models (guinea pig, ferret, cotton rat, pig (including minipigs), rabbit and marmoset). Non-mammalian models are easily tractable model systems to study basic, conserved immune defense pathways and mechanisms. For example, characterization of the Drosophila Toll signaling pathway facilitated the discovery of mammalian Toll-Like Receptors (TLR), which significantly accelerated progress made in the field of innate immunity. Non-mammalian models can be much more easily adapted to high-throughput screening formats than mammalian organisms. Caenorhabditis elegans has been used for whole organism high-throughput screening assays to identify developmental and immune response genes, as well as for drug screening. Many non-mammalian species are natural hosts for human pathogens and share many conserved innate immune pathways with humans, such as the Nf-κB pathway in mosquitoes, the intermediate hosts for Plasmodia parasites. However, studies to better understand immune regulation within non-mammalian models have been constrained by the limited availability of antibodies and other immune-based reagents for use in scientific studies. Certain mammalian models display many features of human immunity but are similarly underutilized due to the limitations noted above. For example, the progression of disease that follows infection of guinea pigs with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), displays many features of human TB. While this model has been used for more than 100 years as a research tool to understand and describe disease mechanisms, immunologic analyses are constrained by the limited availability of immunological reagents specific for the guinea pig. Another example is the ferret model, one of the best animal models of human influenza infection, where immunologic studies also have been limited by the lack of immunological reagents. Project Goal Development and validation of reliable antibodies and reagents for the identification and tracking of primary immune cells or the analysis of immune function/responses (e.g., cytokines, chemokines, intracellular signaling) in specific non-mammalian models or underrepresented mammalian models. Justification should be provided for the selection of proposed targets which may include immune cell markers, receptors with immune function and or other molecules important for immune function. Non-mammalian models are limited to arthropods, amphibians, fish (e.g., jawless, sharks, zebrafish), nematodes, and marine echinoids. Underrepresented mammalian models are limited to guinea pig, ferret, cotton rat, pig (including minipigs), rabbit and marmoset. Phase I Activities MUST include the following activities: • Development of antibodies or other reagents against these targets o If polycloncal antibodies are being developed, the plan also must include the development of monoclonal antibodies • Characterization of antibodies or reagents developed (e.g. confirmation of binding to intended antigen/immunogen) Phase II Activities MAY include, but are not limited to: • Comprehensive evaluation of specificity and functional utility of the reagent(s), such as evaluation of non-specific binding to cells or unrelated molecules and utility of antibodies/reagents for specific indications (e.g., Western blotting, immunoprecipitation, immunohistochemistry, flow cytometry) • Screening for cross-reactivity with related molecules on other non-mammalian species or mammalian immune cells • Optimization (e.g., secondary modifications/conjugations) of the antibodies/reagents for use in different assays and platforms • Scale-up production of the reagents This SBIR will not support: • Identification of immune target molecules and development of antibodies/reagents against immune markers or molecules for animal models not listed in the solicitation • Development of antibodies/reagents for molecules or mechanisms not involved in immune responses • Development of novel or refined animal models
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