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

Description:

 

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

Fast-Track proposals will be accepted Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $300,000/year for up to 2 years; Phase II: up to $1,000,000/year with appropriate justification by the applicant for up to 3 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED

Background:

This goal of this program is to address 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 non-mammalian models (e.g., arthropods, amphibians, fish, nematodes, marine echinoids) and mammalian models for which immunologic reagents are limited (e.g. guinea pig, ferret, cotton rat).

Non-mammalian models are easily tractable model systems to study basic, conserved immune defense pathways and mechanisms. For example, characterization of the Drosophilia Toll signaling pathway facilitated the discovery of mammalian Toll-Like Receptors (TLR), which helped to launch 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-B 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.

There are certain mammalian models that 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 and/or the analysis of immune function/responses (e.g. cytokines, chemokines, intracellular signaling) in non-mammalian models and underrepresented mammalian models.

Phase I Activities must include at least the following 2 activities:

Identification of immune cell markers, receptors with immune function, and other molecules important for immune function; and

•Development of antibodies and/or other reagents against these targets.

Phase II Activities include, but are not limited to:

Validation of antibodies/reagents.

•Screening for cross-reactivity with related molecules on other non-mammalian species and/or mammalian immune cells.

•Scale-up production.

This SBIR Topic will not support:

Identification of immune target molecules and development of antibodies/reagents against immune markers or molecules specifically for mice, rats, dogs, non-human primates or humans.

•Development of antibodies/reagents not involved in immune responses.

•Development of novel or refined animal models

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