The National Institutes of Health (NIH), through several participating organizations including the National Center for Advancing Translational Sciences (NCATS) and institutes such as the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH), is soliciting applications for research on understudied proteins associated with rare diseases. This funding opportunity, named "Pilot Projects Investigating Understudied Proteins Associated with Rare Diseases" (R03 Clinical Trial Not Allowed), invites applications for projects focused on generating preliminary data and research tools for exploring understudied proteins linked to rare diseases. The eligible proteins, which are part of druggable families associated with rare diseases, aim to enhance fundamental research and expand knowledge within rare disease contexts, addressing gaps in the translational research pipeline.

This opportunity supports small, well-defined research projects that could include pilot or feasibility studies, assay development, and the creation of biochemical or biological tools, among other project types. Projects must focus on one or more of the eligible proteins identified in the announcement and must aim to uncover the biological functions of these proteins within the specific framework of rare disease, with the intent to catalyze further studies and future grant applications. The program does not allow clinical trials and targets basic research rather than drug development or clinical applications. Eligible research activities include in vitro protein characterization, animal model studies, development of tools like antibodies or labeled proteins, and validation of protein-disease associations.

Funding for each project is limited to $100,000 in direct costs, with a maximum project duration of one year. The NIH anticipates multiple awards contingent on the availability of funds and the number of meritorious applications received. Applicants from various backgrounds, including early-career researchers and individuals from underrepresented groups, are encouraged to apply. Eligible applicants include higher education institutions, nonprofits, government entities, small businesses, and various regional organizations. Foreign organizations, however, are not eligible to apply.

The application process requires compliance with NIH’s application guidelines, including the use of updated FORMS-I, which will be available before the first application deadline. Key application submission dates for 2025 include February 16, June 16, and October 16, with letters of intent due 30 days prior to these deadlines. Following each submission, scientific merit reviews and advisory council reviews are scheduled, with anticipated project start dates approximately nine to eleven months after submission.

Applications will be evaluated based on three core criteria: the importance of the research, rigor and feasibility of the approach, and the expertise and resources of the applicant team. Projects should demonstrate a strong rationale for studying the understudied protein in a rare disease context, including how the proposed work will overcome key barriers in understanding the protein’s physiological role or potential as a therapeutic target. While preliminary data are not required, applicants must justify their approach using existing literature or related evidence.

This funding opportunity is designed to drive the initial stages of research into rare disease-associated proteins, helping to build the foundational knowledge and resources needed for future translational research efforts. Interested applicants should ensure compliance with NIH policies and complete all necessary registrations, such as SAM, eRA Commons, and Grants.gov, well ahead of the application deadlines. For additional assistance, NIH contacts for scientific, peer review, and financial inquiries are provided within the announcement.