ORIP
Concept Clearance: New
Development of Resources and Technologies for Enhancing Rigor,Reproducibility, and Translatability of Animal Models in Biomedical
Research
Objective: To support research and resource-related research projects aimed atdeveloping broadly applicable technologies, tools, and resources for validating animalmodels and enhancing rigor, reproducibility, and translatability of animal researchFunds Available and Anticipated Number of Awards: Contingent upon NIH
appropriations and the submission of meritorious applications
Award Project Period: 2 to 5 years
Council Action: Vote for approval of the concept for “Development of Resources andTechnologies for Enhancing Rigor, Reproducibility, and Translatability of Animal Models
in Biomedical Research”

Background• Animal models play essential roles in the discovery of basic
biological mechanisms, understanding of the etiology of humandiseases, and development of treatments• Covid-19 vaccines and therapeutics• Diabetes drugs• Significant issues in preclinical research using animal models• High irreproducibility of preclinical studies• High attrition rates of drug development

Background
ORIP Strategic Plan 2021-2025• Facilitate the development and ensure the availability of thehighest quality and most useful animal models and relatedresources for the advancement of research on human disease• Improve and disseminate the best models for humanconditions and diseases that are of interest to multiple NIH
Institutes and Centers• Advance the application of new technologies to support
research resources and improve the generation, care,preservation, and distribution of animal models

https://orip.nih.gov/sites/defaul
t/files/ORIP_Strategic_Plan_20
21-2025_508.pdf

Background
Validation of Animal Models and Tools for Biomedical Research Workshop• Organized by ORIP in collaboration with NHLBI, NIA, NIDDK,NIGMS, and NINDS as 10 virtual sessions in 2020 and 2021.
• Attendees included researchers in and outside of the UnitedStates as well as NIH program officials (200 to 500/session)• Discussed the status and needs regarding the validation andrigor/reproducibility of animal models in biomedical research• Topics included:• Validation of animal models (invertebrates to nonhuman primates)• Tools and resources needed for improving animal research• Strategies for predicting therapeutic outcomes• Integration of data for improving animal researchhttps://orip.nih.gov/about-orip/workshop-reports

Recommendations from the Workshop• Improving genetic technologies for mutating and tagging genes, developing
humanized animal models and nanoantibodies, detecting interacting proteins in cells• Systematically phenotyping animal models at multiple levels (e.g., single-celltranscriptomics, proteomics, tissue, organ, cell morphology, metabolomics, behaviors)• Screening technologies (i.e., high-throughput genetic and chemical screens)• Artificial intelligence strategies that allow integrative mining of data in various
databases (e.g., model organism databases, phenotype databases)• Standardization and reporting of genetic background of strains, housing condition,and environmental conditions (i.e., to promote reproducibility)• Sophisticated imaging facilities• Enhancing stock centers
https://orip.nih.gov/sites/default/files/Validation_Session_X_Mee
ting_Report_Final_508.pdf

Purpose of the New Initiative• Support research and resource-related research projects aimed at developing
broadly applicable technologies, tools, and resources for validating animal models
and enhancing rigor, reproducibility, and translatability of animal research• To align with ORIP’s NIH-wide mission, proposed projects must:• Have broad application to multiple NIH Institutes and Centers• Explore multiple body systems or evaluate diseases that impact multiple body systems• To align with ORIP’s Strategic Plan, proposed projects must:• Develop resources and technologies that have significant impact across a broad range of
research areas using animal models• Demonstrate how proposed resources and technologies impact rigor and reproducibility ofanimal studies• In alignment with its mission, ORIP will seek input from NIH Institutes and Centersin addressing identified resource gaps and needs, including:• Animal model validation technology, resource, and tool development• Artificial intelligence strategies• Deep integration

Examples of Suitable Projects• Resources or technologies to facilitate phenotyping at multiple scales (single-cell, tissue,organ, whole organism)• Technologies, including artificial intelligence tools, for integrating multi-omics,
biochemical, physiological, morphological, and behavioral data
• Strategies that allow user-friendly informatic searches and integrative mining of data forcomparative human-animal biology• High-throughput imaging technologies for integrative analysis of cells and cellularnetworks across animal species• Resources that facilitate collaborations between basic science and clinical researchers
in the use of multiple animal models for studying human diseases (vertical integration)

Examples of Grant Mechanisms
Grant mechanisms to support this initiative could be, but are not limited to:• R21 for 2-year exploratory/developmental research projects• R01 for 5-year research projects• R24 for 4-year resource-related research projects• U24 for 4-year resource-related research projects under cooperative agreements• Small business grant mechanisms

Concept ClearanceVote for approval of the concept for“Development of Resources and Technologies
for Enhancing Rigor, Reproducibility, andTranslatability of Animal Models in BiomedicalResearch”