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This Notice of Funding Opportunity (NOFO) invites grant applications from institutions/organizations that propose to build a Medical Rehabilitation Research Center. The centers will have a specific rehabilitation research theme and be comprised of a research project supported by 3 cores. The 3 cores will have functions within the center as well as functions nationwide. Together, the cores will support: administrative functions (including an optional pilot program), resource sharing, and community engagement and outreach. The Medical Rehabilitation Research Centers will contribute tomedical rehabilitation research infrastructure by developing and disseminating techniques, data, theories, research programs, and expertise with the goal of enhancing the capability of medical rehabilitation investigators to understand mechanisms of functional recovery, develop therapeutic strategies, identify clinical care gaps, and improve the lives of people with disabilities. Applications must include a plan for inclusion of People with Lived Experience (as a required other attachment) that is relevant to the research theme of the center and increases the potential impact of the center.

The objective of this Notice of Funding Opportunity (NOFO) is to invite new and renewal applications for the Rare Diseases Clinical Research Consortia (RDCRC) that comprise the Rare Diseases Clinical Research Network (RDCRN). The RDCRCs are intended to advance and improve diagnosis, management, and treatment of numerous, diverse rare diseases through highly collaborative, multi-site, patient-centric, translational and clinical research. Special emphasis will be placed on the early and timely identification of individuals with rare diseases and clinical trial readiness.

The purpose of this Alzheimers Disease-Related Dementia (ADRD) initiative is to promote the development and distribution of innovative technologies, methods, protocols, and biomedical materials that enhance combined human neuropathology and neuroimaging research with data aimed at understanding the underlying pathophysiology of in vivo imaging results typically associated with vascular contributions to cognitive impairment and dementia (VCID) in TBI-related dementia and other ADRD diagnoses. Resources developed under this FOA must follow open data sharing practices and are intended to expand the broader research communitys capacity to perform research aimed at neuropathologically-informed understanding of the vascular pathophysiology of clinically-relevant, in vivo neuroimaging findings.

This notice of opportunity announcement (NOFO) is issued by the National Institute of Neurological Disorders and Stroke to enable submission of program project grant applications that propose to conduct innovative, interactive research to answer significant scientific questions that are important for the mission of NINDS, via a synergistic collaboration between outstanding scientists who might not otherwise collaborate. The program project grant is designed to support research in which the funding of several interdependent highly meritorious projects as a group offers significant scientific advantages over support of these same projects as individual research grants.

"Fluctuating cognition can occur in many types of dementia and is a core clinical feature of Dementia with Lewy Bodies. Cognitive fluctuations can last from seconds to days, are unpredictable (e.g., do not just occur in the evenings, as with sun-downing), and are associated with poor daily functioning for the patient. A number of small studies have suggested that cognitive fluctuations in subjects with dementia may be related to epileptiform discharges and impaired oscillatory activity on EEG, but it is not clear that these are the only factors involved in patient populations that often experience dysautonomia, orthostasis, and sleep disturbances. The etiology of cognitive fluctuations may be multi-factorial and may vary in different dementia populations. Understanding the physiology related to cognitive fluctuations is a critical next step to the development of treatment approaches and improving quality of life for these patients. This initiate would encourage research that will better characterize the physiology responsible for cognitive fluctuations in ADRD populations. Given their variable appearance and time course, it is anticipated that wearable digital devices will be important for capturing fluctuations in a timely fashion, and applicants should consider incorporating those device(s) capable of acquiring the relevant data to support the hypothesized mechanism(s). Applicants may focus on assessing multiple mechanisms in a specific ADRD population, or may chose to compare mechanisms across multiple types of ADRDs. "

This Notice of Funding Opportunity (NOFO) invites applications for a U54 Specialized Center (henceforth: Consortium) to provide resources, expertise, and coordination to advance innovative, high-quality research on palliative care for those with serious illness across the lifespan. This research infrastructure will encompass Alzheimers disease and Alzheimers disease-related dementias (AD/ADRD), cancer, and other serious illnesses and populations relevant to the partnering Institutes, Centers, and Offices (ICOs). NIH currently funds many palliative care research projects across the ICOs, and there is a need for a structure to leverage synergies, coordinate efforts, develop the scientific workforce, and address remaining gaps in the field. The goals of this initiative include generating new scientific knowledge, in part through supporting pilot and exploratory studies; fostering development of early- and mid-career palliative care investigators; serving as a national platform to provide research resources and facilitate high-quality palliative care research; engaging healthcare systems and community-based organizations as research partners and settings for palliative care research; and disseminating research findings, best practices, data, and other impactful resources to the palliative care research and clinical communities. An important focus of the Consortiums work will be on facilitating research to understand and address disparities in access, quality, and use of palliative care services for health disparities populations or in underserved areas.

This BRAIN Initiative Notice of Funding Opportunity (NOFO) is to scale up efforts for viral, non-viral, transgenic, and gene regulatory element screening technologies and create reagent resources to access brain cell types. This NOFO is part of the BRAIN Initiative Armamentarium for Brain Cell Access transformative project. Reagent development efforts will apply gene transfer, gene regulation, genome engineering, activity sensor/effector, and atlasing technologies for use in both genetically tractable and less tractable systems, including primates and human tissue, which are relevant for future translational efforts. Reagent validation studies will provide feedback to improve scaled resources, informed by deeper understanding of neural gene transfer and regulation mechanisms. Precise targeting could ultimately aid in human disorders, for example, by providing access for gene editors to specific cell types to repair mutations.

This NOFO would support development and validation of novel clinically- and/or pathophysiologically-relevant human cellular models of ADRD. The cellular model systems would be expected to capture the multi-faceted pathologies and multiple cell types observed in ADRDs. Validation includes internal, face, construct, and predictive (to the extent possible) validation. These models can be developed/validated with the goal of supporting therapy development or better understanding of human disease mechanisms and mechanisms that uncover predisposition to developing neurodegenerative dementias. Human cellular models need to be novel, complex, and address a gap in the currently available models. Multidisciplinary teams will be highly encouraged. Leveraging the use of and depositing new cells into existing NIH cell repository resources will also be encouraged.

This NOFO would support investigations with a minimum of two relevant co-pathologies (e.g., tau, alpha-synuclein, TDP-43, TMEM106B, vascular), with optional risk factors and co-morbidities, to identify cellular and molecular mechanisms of how/why multi-proteinopathy interactions drive worsening neurodegenerative processes and phenotypic outcomes. Studies should examine co-pathology cellular and molecular interactions across brain regions and time in proximate cell population, across various intracellular dynamics and localization, and upstream and downstream from aggregated protein states to determine what events lead to worse phenotypic outcomes.

This FOA would support establishing deeper mechanistic insight and causal relationships between TDP-43 pathology and phenotypic outcomes, as well as mechanistic interactions between TDP-43 and other co-pathologies, such TMEM106B. Additionally, it would include comparisons (including mechanistic, molecular, structural, cellular, genetic, -omic, anatomical, neuropathological, etc.) between TDP-43 proteinopathies, including LATE, with or without AD-NC, and FTD and/or ALS.