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 Mission: IID or BioD or both: both COR: Joy Liu 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 program addresses the limited availability of reagents (e.g., antibodies, 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 include amphibians, arthropods, fish (e.g., jawless fish, sharks, zebrafish), marine echinoids, and nematodes; and under-represented mammalian models of interest include bats, cats, cotton rats, dogs, ferrets, guinea pigs, hamsters, marmosets, minks, pigs (including minipigs), rabbits, and sheep. Many non-mammalian models are easily tractable model systems to study basic, 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 accelerated progress in the field of innate immunity. Nonmammalian 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 Page 112 pathogens and share many conserved innate immune pathways with humans, such as the NF-kB pathway in mosquitoes, the intermediate hosts for Plasmodia parasites. However, studies to better understand immune regulation within nonmammalian models have been constrained by the limited availability of antibodies and other immune-based reagents. 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, sheep are useful for understanding the role of the immune system in pregnancy and in xenotransplantation studies. However, the lack of high-quality immunologic reagents for sheep immune markers continues to slow advances in these areas. Minks are highly susceptible to SARS-CoV-2 infection with the potential for zoonotic pathogen transmission. However, there are almost no reagents available for immunological studies in this species. Similarly, bats are the natural reservoir and vectors for several major zoonotic diseases that cause severe human diseases, but the lack of reagents has impeded studies of how bats' adaptive or innate immune responses control these pathogens without the manifestation of disease. Advances have been made recently in the development of reagents for a number of these under-represented mammalian and non-mammalian models, and relevant immune reagents may already be commercially available. Therefore, offerors are urged to focus on potential targets for which no antibodies are available, or for which commercially available reagents do not perform well in specific assays, produce inadequately strong signals, or have undesirable off-target effects. Proposals that focus on targets for which sub-optimal reagents already exist must include the corresponding commercially available reagent(s) as a comparator