Through Notice of Special Interest (NOSI): Using the Collaborative Cross (CC) Mouse Model for Immunoregulatory and Infectious Disease Research, NIAID invites applicants to propose research that develops and validates use of Collaborative Cross (CC) mouse models to reproduce the impact of host genetic variations on human immune system responses and screens and evaluates mouse lines for use in specific studies and disease models within NIAID’s mission areas.
Although the use of mice as model organisms for immunology research has led to significant advances in understanding the mechanisms of human immune activation and regulation, most mice lines lack the genetic diversity needed to replicate more complex and diverse genetic responses found in humans.
CC mouse lines can overcome limitations as model organisms for immunology research by modeling the diversity of human genetics. The CC is a collection of recombinant-inbred (RI) mouse lines derived from initially randomized crosses of eight genetically diverse variations present in the genomes of laboratory mice.
Research Objectives
The purpose of this NOSI is to validate the utility of CC mouse lines to 1) reproduce human immune responses more faithfully and advance the understanding of host genetics involved in immune regulation/function and 2) select and evaluate CC and CC-recombinant inbred intercrosses (CC-RIX) mouse lines suitable for specific studies and disease models within research areas of interest to NIAID.
NIAID’s research areas of interest include the following:
- Studies of immune system development, regulation, and function during homeostasis or in response to or for protection from pathogenic infections; vaccines; environmental, food, or drug allergens; autoantigens; or allo- or xeno-antigens.
- Studies of changes in immune regulatory and functional mechanisms across the lifespan.
- Development and characterization of new models for autoimmune diseases and asthma and allergic diseases that better predict the human clinical experience.
- Identification of genetic determinants underlying autoimmune diseases, primary immunodeficiency diseases, routes of allergic sensitization, differences in sensitivity to allergens, and response to allergen-specific immunotherapy.
- Genetic evaluation of major histocompatibility complex region diversity of CC and CC-RIX mouse lines and its influence on transplant outcomes; characterization of biomarkers that predict allo- or xeno-graft rejection or promote transplant tolerance without compromising protective immunity.
- Studies of infectious disease pathogenesis with the goal of identifying:
- Novel targets or antigens for vaccine development and therapeutics development.
- Novel animal models for infectious disease research.
- Infectious disease-related biomarkers for predicting susceptibility to infection or infectious diseases and response to therapeutics or vaccinations, diagnosis of individuals infected with pathogens or exposed to toxins, and assessment of disease progression in acute and chronic infectious diseases.
Overall, we highly encourage validation of the genetic factors identified in CC lines with human samples or human studies for all proposed studies.
Nonresponsive Areas of Research Interest
Note that we consider the following research areas to be nonresponsive to this NOSI:
- Studies of immune mechanisms related to cancer development and treatment or HIV infection and treatment.
- Studies of hematopoietic stem cell or bone marrow transplantation, including graft-versus-host disease, unless performed in the context of organ or pancreatic islet allo- or xeno-plantation, vascularized composite allo-transplantation, or studies of hematopoietic stem cell transplantation for autoimmune diseases.
- Studies utilizing mouse strains other than the CC and CC-RIX mouse resources.
- Studies only using in vitro systems with cells from CC or CC-RIX mice.
- Clinical trials.
Application and Submission Information
This notice applies to due dates on or after October 5, 2024, and subsequent receipt dates through July 16, 2027. Apply to this initiative using one of the following notices of funding opportunity (NOFOs) or any reissues of these announcements through the expiration date of this notice.
- NIH Research Project Grant (Parent R01, Clinical Trial Not Allowed)
- NIH Exploratory/Developmental Research Project Grant (Parent R21, Clinical Trial Not Allowed)
You must follow all instructions in the SF 424 (R&R) Application Guide and the NOFO through which you applied. Be sure to include “NOT-AI-24-054” in the Agency Routing Identifier field box (box 4B) of the SF 424 R&R Form.
Contact Information
Send inquiries to NIAID’s scientific/research contacts, Dr. Qian “Joy” Liu at liujoy@niaid.nih.gov or 301-761-6621 and Dr. Kaitlyn Morabito at dambachkm@mail.nih.gov or 301-761-6972.