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"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. "

NIAID announces the availability of funds for administrative supplement awards to promote the development of pediatric chemical research models and medical countermeasures (MCM) discovery under the Chemical Countermeasures Research Program (CCRP). There is currently an unmet need in understanding the natural history, pathophysiology, and treatment of critical illness in infants, children, adolescents, and young adults after exposure to highly toxic DHS-designated Chemicals of Concern (CoCs). The administrative supplement funds are intended to support pilot preclinical projects by CCRP-supported researchers that focus on 1) Basic research to elucidate mechanistic differences in susceptibility to CoCs between pediatric and adult populations and/or 2) Applied research towards the discovery and early development of pediatric-safe MCMs.

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.

The NIH Research Education Program (R25) supports research education activities in the mission areas of the NIH. The over-arching goal of this National Insitute of Neurological Disorders and Stroke R25 program is to support educational activities that complement and/or enhance the training of a workforce to meet the nations biomedical, behavioral and clinical research needs.To accomplish the stated over-arching goal, this FOA will support creative educational activities with a primary focus on research experiences, designed to foster the development of physicians as research scientists in areas relevant to the NINDS mission. The research experiences will prepare clinicians to successfully compete for individual NIH mentored career development awards, or where appropriate, independent research awards. This FOA will also support educational activities such that participants of the R25 are expected to attend and participate in an annual workshop specific to this FOA to present their work, discuss progress and plans towards transitioning to the next career stage and to network with other researchers and leaders in their fields. Such success will facilitate their transition from resident/fellow to physician-scientist, and will thus foster retention of a cadre of physician-scientists who will conduct research into the mechanisms of, etiology, and treatment of neurological diseases.

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.

The Transformative Research to Address Health Disparities and Advance Health Equity initiative is soliciting applications to support unusually innovative intervention research addressing social determinants of health (SDOH) which, if successful, would have a major impact on preventing, reducing, or eliminating health disparities and advancing health equity. Projects should clearly demonstrate, based on the strength of the logic, a compelling potential to produce a major impact on advancing NIHs commitment to addressing SDOH to accelerate progress in improving health for all. Preliminary data are not required for this initiative.

The NIH Office of Science Policy (OSP) within the Office of the Director (OD) announces the availability of administrative supplements to support 1) research on bioethical issues to develop or support the development of an evidence base that may inform future policy directions, and/or 2) certain efforts to develop or augment bioethics research capacity. Applicants may propose to supplement parent awards focused on bioethics or to add a component related to bioethics in a biomedical and/or health-related behavioral research study. The bioethics question, issue, or topic must be clearly articulated. Note that applications must be within the general scope of the parent award.