Pilot Centers for Precision Disease Modeling (U54)(Clinical Trials Not Allowed)
NIH - National Institutes of Health (PAR-20-085)
- Proposal: 03/24/2020
- Amount: $1.25m per year
- Duration: 5 years
This funding opportunity announcement (FOA) encourages Cooperative Agreement (U54) applications from institutions/organizations for Pilot Centers for Precision Disease Modeling which will establish pipelines for preclinical scientific discovery, disease modeling and development of clinical interventions based on innovative animal models. These pipelines eventually will be integrated into diagnostics, care and therapeutic treatment of human patients. The goal of the program is to support collaborative research projects that link current personalized medicine efforts in humans with advances in animal genomics and technologies for genetic manipulation to enhance the predictive value of preclinical studies. Optimization of this collaborative effort may be accomplished by linking existing programs within a single institution and/or by reaching across multiple institutions. This program will support a limited number of Centers that will function as focal points to define, test, and use the principles, knowledge, and expertise needed to address the unique requirements of individual patients or groups of patients. The Centers will start working on several demonstration projects and then will focus on high-throughput projects, which will be nominated by the research community on local, regional and national bases and selected by each Center’s Steering Committee. It is expected that a specific Center will maintain multifaceted research activities to build and study model systems that can be adjusted as required to accommodate a broad spectrum of diseases. Applications to develop animal models that relate strictly to a specific disease or category of research will not be considered for funding. For example, applications from investigators interested in models or model systems with a primary focus on heart disease, neurological disorders or cancer would not be considered acceptable. Furthermore, ORIP only supports studies that are related to the interests of multiple NIH Institutes and Centers. Applications proposing studies that are related predominantly to the interest of one NIH Institute or Center (IC) and only peripherally to the interests of other ICs will be withdrawn.. Resources created by the Centers and related services will be provided to the biomedical community. Each Center should have a set of required components, including a Preclinical/Co-Clinical Section, which will be responsible for the collection of patient-specific information and will facilitate reciprocal interactions with clinical studies, conducted elsewhere. This approach recognizes a number of critical needs: an effective collaboration between clinical and research studies; a centralized service to process medical, genetic and other omics information; improved phenotype-disease ontologies; comparative medicine research; creation of genetically/somatically modified animal models in the most appropriate species; and the ability to test the predictive validity of newly created disease models in preclinical applications.
The objectives of the Pilot Centers for the Disease Modeling program include, but are not limited to:
- Improving methods to rapidly model disease-specific genomic alterations, including robust phenotyping to assess if specific genetic changes recapitulate a human phenotype.
- Creating new and improved disease taxonomy and phenotype ontologies to better assist translation of specific patient information to the most appropriate animal model systems and disease categories. Developing an efficient validation process for incorporating animal model data into a knowledge network related to a specific disease and a new taxonomy.
- Accelerating testing of new targeted therapies using animal models.
- Stratifying potential patient responses on the basis of genetic/omics criteria.
- Developing combinatorial treatments.
- Repurposing drugs and optimizing treatments for rare orphan diseases.
- Discovering and developing predictive, reliable biomarkers across species, including humans.
- Developing a co-clinical program that will standardize protocols for animals and humans, which should closely match each other in terms of both data acquisition and data analysis, and be efficiently communicated among basic, clinical and pharmaceutical researchers.
- Developing systematic approaches to functional genomic validation of potential causes of disease and markers of therapy response/sensitivity, which along with the use of the model organisms can include cell-based models. Providing a foundation for the development of drugs and therapeutics tailored to specific genetic profiles.
- Projects that go beyond testing of a limited number of genomic variants, but rather evaluate large-scale genomic data using a variety of high-throughput technologies are highly encouraged.
Centers, being NIH-funded centralized resources, should provide development plans for wide access and use by the research and medical communities in diverse fields of diagnostics, new therapeutics and effective preventive medicine strategies. This includes a mechanism for outreach and awareness to the broader research community, and deposition of data and models in a publicly accessible repository system. Leveraging available institutional support and other resources and identifying a clear path to sustainability of the successful implementation project are strongly encouraged.
Oleg Mirochnitchenko, Ph.D.
Office of Research Infrastructure Programs (ORIP)