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: 3-6 Budget (total costs): Phase I: $300,000 per year for up to 2 years Phase II: $500,000 per year for up to 3 years Background This program addresses the need of reagents (e.g., antibodies, tetramers, immune receptor ligands) for the identification and discrimination of immune cells and the characterization of immune responses in non-mammalian models and/or in specific underrepresented mammalian models. Non-mammalian models of interest are amphibians, arthropods, fish (e.g., jawless fish, sharks, zebrafish), marine echinoids, and nematodes; and under-represented mammalian models of interest are bat, hamster, ferret, guinea pig, white-footed mouse, chicken, bird, cat, cotton rat, dog, marmoset, mink, pig (including minipigs), rabbit and sheep. Non-mammalian models are easily tractable model systems to study basic and conserved immune defense pathways and mechanisms. For example, the characterization of the Drosophila Toll signaling pathway facilitated the discovery of mammalian Toll-Like Receptors (TLR), which significantly sped up progress in innate immunity. Likewise, the zebrafish have been deployed to examine hematopoiesis, immune cell development and migration. 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 some conserved innate immune pathways with humans, such as the NF-kB pathway in mosquitoes, the intermediate hosts for Plasmodia parasites. Nevertheless, the limited availability of antibodies and other immune-based reagents has constrained studies to better understand immune regulation within non-mammalian models. Certain mammalian species display specific features of human immunity that make them highly valuable models but are similarly underutilized due to the limitations noted above. For example, although sheep are useful for understanding the role of the immune system in pregnancy and in xenotransplantation studies, the lack of high-quality reagents for sheep immune markers continues to impede the advances in these areas. Some mammalian species are natural reservoirs for many human pathogens and could be great models for studying immunity to these pathogens. Minks are highly susceptible to SARS-CoV-2 infection, with the potential for zoonotic pathogen transmission, but almost no reagents are available for immunological studies in this species. Similarly, even if bats and white-footed mice are the natural reservoirs for several major zoonotic diseases that cause severe human diseases, the scarcity of reagents has hindered studies of how the adaptive or innate immune responses of bats or white-footed mice control these pathogens without any manifestations of disease. Advances have been made recently in developing reagents for a number of these under-represented mammalian and nonmammalian models, and immune reagents may already be commercially available. Therefore, offerors are urged to focus on potential targets that no antibodies are available, or commercially available reagents do not perform well in specific assays, such as produce weak signals, or have undesirable off-target effects. Proposals that focus on targets that have suboptimal existing reagents must include the corresponding commercially available reagent(s) as a comparator.