Engineering Next-Generation Human Nervous System Microphysiological Systems (R01 Clinical Trials Not Allowed)

The National Institutes of Health (NIH), with the participation of five institutes (NIA, NEI, NIAAA, NIDCD, and NIMH), has announced funding opportunities for research through the "Engineering Next-Generation Human Nervous System Microphysiological Systems" (MPS) program, under the R01 Research Project Grant. This initiative focuses on the development of advanced human cell-based MPS and related assays that replicate nervous system architectures and physiology for investigating nervous system development, function, and aging. This opportunity, which does not allow clinical trials, invites applications aiming to advance MPS technology to a new level of fidelity, going beyond current models to address neurological and age-related diseases and other disorders. The purpose of this program is to stimulate research that bridges technology development and basic biology. The MPS models should incorporate complex structural and functional characteristics of the nervous system, including brain and sensory organ systems, and are expected to be applicable to understanding cellular and circuit-level maturation, connectivity, and aging. Key areas include creating multi-lineage structures that represent nervous system function under both normal and disease states, particularly those affected by complex conditions. Researchers working at the feasibility stage with high-risk or conceptual projects may consider applying under the associated R21 opportunity, specifically designated for early-stage exploration. This funding opportunity seeks a wide range of innovative approaches to developing sophisticated models, such as integrating novel substrates, bioreactors, and 3D printing methods; supporting diverse nervous system cell types; and establishing complex connections that mirror human brain architecture. It encourages high-impact designs that enable reproducible measurements of human-relevant neural activity over time and involve MPS technology that substantially exceeds current levels of tissue organization and cellular integration. Models should also aim to reproduce physiological support systems, such as cerebrospinal fluid flow or the blood-brain barrier, as part of the model’s development. Each participating NIH institute has specific interests. NIMH seeks projects that represent cognitive, social, and affective brain functions, aiming to understand mental health conditions. NEI is interested in MPS models related to the visual system and assessing MPS improvements over existing animal models. NIAAA focuses on using MPS to examine alcohol’s impact on neural circuits, including during development and aging. NIDCD is interested in MPS innovations to study communication disorders and sensory functions. NIA prioritizes MPS systems that replicate aging brain functions and diseases such as Alzheimer’s. All projects are encouraged to include advanced validation processes, data-sharing plans, and collaborative strategies with expert partners. Eligible applicants include higher education institutions, nonprofits, for-profits, and various governmental organizations, including state, local, and tribal governments. Foreign organizations and components of U.S. organizations are also eligible. Applicants must complete registrations through SAM, eRA Commons, and Grants.gov. Applications should follow NIH’s rigorous data management and sharing plans, and NIH strongly encourages the dissemination of resources and data generated. Proposals should detail the current technological benchmarks and describe how the new MPS models will surpass these. Review criteria will focus on the significance, innovation, and rigor of the scientific approach, with consideration of applicant expertise and institutional support. Key dates include submission deadlines beginning February 5, 2025, with subsequent rounds in June and October 2025. The award budget is unrestricted but must align with project needs, and the maximum project period is five years. Interested applicants should consult NIH guidelines, including relevant notices, to ensure compliance with all requirements. NIH will conduct a peer review, assessing scientific merit based on innovation, feasibility, and potential impact on advancing nervous system research.