Description:
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
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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
