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The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application. The development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest or approaches that are expected to target specific cell types and/or circuits in the nervous system with greater precision and sensitivity than currently established methods are encouraged. Tools that can be used in a number of species/model organisms rather than those restricted to a single species are highly desired. Applications that provide approaches that break through existing technical barriers to substantially improve current capabilities are highly encouraged.

The purpose of this Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to encourage applications that will develop and validate novel tools to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. The new tools and technologies should inform and/or exploit cell-type and/or circuit-level specificity. Plans for validating the utility of the tool/technology will be an essential feature of a successful application. The development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest or approaches that are expected to target specific cell types and/or circuits in the nervous system with greater precision and sensitivity than currently established methods are encouraged. Tools that can be used in a number of species/model organisms rather than those restricted to a single species are highly desired. Applications that provide approaches that break through existing technical barriers to substantially improve current capabilities are highly encouraged.   

CZI seeks applications aimed toward identifying unifying principles that underlie tissue homeostasis and inflammation at the single cell level. Our goal is to stimulate collaborations across disciplines that will help define a new field. Successful applications will bring together researchers in different experimental, computational, or medical domains. They will address local cell properties and interactions in inflamed tissues and compare them to the properties and interactions of similar cells in healthy tissues. They will increase our understanding of the cell types that mediate inflammation, and their interactions in space and time. The two-year pilot grant period is intended to develop proof-of-concept for the experimental team and the approach, setting up future programs for detailed mechanistic investigations. 

This Funding Opportunity Announcement (FOA) intends to support pilot studies aimed to establish molecular, anatomical, and functional cell and circuit census data from selected brain regions of young and old C57BL/6J mice. This will complement and build on current BRAIN Initiative efforts while informing a design for a comprehensive characterization of cells and circuits in the brain across the lifespan, including the generation of a comprehensive 3D brain cell reference atlas of the aging mouse brain.

The goal of this FOA is to define and characterize neural cell populations, neural circuits, and brain networks and regions that are vulnerable to brain aging and Alzheimer's disease (AD). Understanding mechanisms underlying selective vulnerability from cells to networks in AD is critical to fully define the disease process and to develop effective therapies. 

The goal of this FOA is to define and characterize neural cell populations, neural circuits, and brain networks and regions that are vulnerable to brain aging and Alzheimers disease (AD). Understanding mechanisms underlying selective vulnerability from cells to networks in AD is critical to fully define the disease process and to develop effective therapies.

The Ellison Medical Foundation Senior Scholar program is designed to support established investigators working at institutions in the U.S. to conduct research in the basic biological and basic biomedical sciences relevant to understanding lifespan development processes and age-related diseases and disabilities. The award is intended to provide significant support to allow the development of new, creative research programs by investigators who may not currently be conducting aging research or who wish to develop new research programs in aging. The Foundation particularly seeks to stimulate new research that has rigorous scientific foundations but is currently inadequately funded, either because of its perceived novelty, high risk, or because it is from an area where other "traditional" research interests absorb most funding. Areas of interest include, but are not limited to Structural biology Molecular genetics Studies with model systems ranging from lower eukaryotes to humans Inquiries testing the relevance of simpler models to human aging Genetic epidemiology of aging; candidate longevity genes Aging in the immune system Host defense molecules in aging systems Mechanisms of free radical induced cell aging Mechanisms of aging in various differentiated cell populations Gene/environment and gene/gene interactions Integrative physiology New approaches to age-modulated disease mechanisms

Recent reports highlight the enormous spatial and temporal diversity of glia, even within the same glial cell type. This within-glial-cell-type heterogeneity evolves during aging, suggesting that subtypes of glia with distinct physiological roles could emerge to influence brain aging processes. The goal of this Funding Opportunity Announcement is to support research addressing critical knowledge gaps in our understanding of how these glial subpopulations could contribute to vulnerability and resilience to brain aging.

The participating NIH Institutes and Centers invite applications to address both the origins and the effects of low level chronic inflammation in the onset and progression of age-related diseases and conditions. Chronic inflammation, as defined by elevated levels of both local and systemic cytokines and other pro-inflammatory factors, is a hallmark of aging in virtually all higher animals including humans and is recognized as a major risk factor for developing age-associated diseases. The spectra of phenotypes capable of generating low-level chronic inflammation and their defining mediators are not clear. Further, a clear understanding of how chronic inflammation compromises the integrity of cells or tissues leading to disease progression is lacking. The role of dietary supplements and/or nutritional status in chronic inflammation in age-related disease is also poorly studied. Thus, there is a critical need to establish the knowledge base that will allow a better understanding of the complex interplay between inflammation and age-related diseases. Applications submitted to this FOA should aim to clarify the molecular and cellular basis for the increase in circulating inflammatory factors with aging, and/or shed light on the cause-effect relationship between inflammation and disease, using pre-clinical (animal or cellular based) models.

This funding opportunity invites applications that integrate the use of computational approaches to identify individual drugs currently used for other conditions with potential to be efficacious in AD or AD-related dementias (as single drugs or as drug combinations) with proof-of-concept efficacy studies in cell-based models, animal models and/or humans. 

This FOA invites exploratory comparative biology research projects assessing how different animal species respond to challenges and damage to cellular physiology pathways that might influence the onset of Alzheimer's and other neurodegenerative diseases as well as resilience to them, such as adaptation to stress, macromolecular damage, proteostasis and stem cell function and regeneration.    

The "Mechanisms of cellular death in NeuroDegeneration" (MCDN) funding program's overall goal is to discover and understand the mechanisms and pathophysiological processes by which brain cell loss is mediated in disease and thereby seek insights and potential targets for therapeutic interventions that would sustain healthy brain function.

The purpose of this FOA is to invite: 1) descriptive studies to identify putative juvenile protective factors, 2) experimental studies to test hypotheses about their effects on aging and 3) translational studies to characterize potential beneficial and adverse effects of maintaining or modulating the level of juvenile protective factors in adult life. Juvenile protective factors (JPFs), intrinsic to an immature organism, help to maintain or enhance certain physiological functions across all or some stages of postnatal development (i.e., segment of the life span between birth and sexual maturity), but diminish or disappear as the organism transitions from one maturational stage to the next. The loss or diminution of JPFs after a given stage of postnatal development or at time of sexual maturity may contribute to the onset of deleterious aging changes (e.g., compromised stem cell function and reparative capacity) across adulthood. This FOA is uniquely focused on animal and clinical studies which involve comparisons between juvenile versus adult states or between stages of postnatal development to identify putative JPFs and their effects on aging. 

This FOA invites applications that will systematically and comprehensively characterize alpha-synuclein and amyloid-beta subspecies present in human Lewy Body Dementia (LBD) post-mortem brain tissue, identify toxic subspecies and potential mechanisms of toxicity, and characterize any interactions between the proteins that may contribute to increased toxicity and/or explain selective vulnerabilities of cells/circuits. Applications are required to include at least 3 hypothesis-driven projects that address these goals, an administrative core, and other cores as appropriate. Applicants will be expected to focus on the use of human tissues. All applications will be expected to include plans for developing a publicly-available library of fully characterized alpha-synuclein and amyloid-beta subspecies found in LBD.

The purpose of the FOA is to support the large scale molecular platform analysis of brain tissue, human biofluid or human induced pluripotent stem cell resources for the identification of targets and pathways associated with Alzheimer's Disease Related Dementias (ADRDs) pathophysiology.

Since 1998, ADDF has provided more than $29 million in funding for early stage clinical drug trials for Alzheimer's disease and related dementias. To help propel novel drugs into the clinic, ADDF also has provided over $6.5 million in support of final preclinical studies required by regulatory agencies for the initiation of clinical research studies. The goal of the foundation's PACT program is to increase the number of innovative treatments tested in humans for Alzheimer's disease and related dementias. To that end, the program will fund clinical trials through Phase 2a of novel drug candidates, including small molecules and biologics (antibodies, oligonucleotides, peptides, gene therapies, cell therapies); proof-of-concept biomarker-based trials in patients for repurposed/repositioned drugs; and regulatory studies for investigational new drug (IND)/clinical trial application preclinical packages that are required before testing novel drugs in human subjects. Proposed molecular targets will be evaluated based on the strength of available evidence linking the target to the disease and demonstrating that modulating its biological activity will improve symptoms or modify disease progression. Current target areas of interest include but are not limited to neuroprotection, inflammation, vascular function, mitochondria and metabolic function, proteostasis, ApoE, epigenetics, and synaptic activity and neurotransmitters.

The purpose of the FOA is to support the structural characterization of protein species associated with Alzheimer's Disease Related Dementias (ADRDs) through the utilization of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) of proteins expressed in human tissue and cell sources. Studies in response to this RFA should also include the development of research tools and resources to further characterize/validate the protein species.

The purpose of the FOA is to support the structural characterization of protein species associated with Alzheimer's Disease Related Dementias (ADRDs) through the utilization of cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) of proteins expressed in human tissue and cell sources. Studies in response to this RFA should also include the development of research tools and resources to further characterize/validate the protein species. This FOA is in response to the Alzheimer's Disease Related Dementias (ADRD) challenges outlined in the 2016 update to the National Plan to Address Alzheimer's Disease.

The focus of this Funding Opportunity Announcement (FOA) is on in vivo human studies, and in vitro studies on human cells or tissues, aimed at potential identification of therapeutic targets or and/or testing of interventions for healthy aging. Potential therapeutic targets include FOXO3 itself and upstream and downstream regulators in pathways mediated by FOXO3. The range of research areas of interest in this FOA includes studies that: 1) examine in vivo phenotypic effects of human FOXO3 variants, and/or 2) elucidate effects of these variants on cellular functions and the pathways that mediate them, and/or 3) identify and evaluate candidate therapeutic targets (e.g., target validation studies, testing of candidate compounds) for potential interventions based on FOXO3 functional pathways. Projects involving whole genome sequencing of new or existing cohorts are outside the scope of this FOA. However, targeted resequencing on a limited sample set in an existing cohort could be supported by this FOA.

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) InitiativeSM is aimed at revolutionizing our understanding of the human brain. By accelerating the development and application of innovative technologies, researchers will be able to produce a new dynamic picture of the brain that, for the first time, will show how individual cells and complex neural circuits interact in both time and space. It is expected that the application of these new tools and technologies will ultimately lead to new ways to treat, cure, and even prevent brain disorders.

Age is the number one risk factor for diagnosis of many age-related lung diseases, including COPD and pulmonary fibrosis. Despite this, little is known regarding the interactions that likely occur between the molecular and cellular mechanisms of disease and the changes in molecules and cells that can be attributed to normal aging. In fact, very little is known about the normal aging process in the lung at the cellular and molecular level. In 2015, the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Aging (NIA) co-sponsored a workshop that identified a major knowledge gap in the understanding of normal lung aging in humans, as well as the need to develop a map of molecular changes that occur during normal aging in the lung that can serve as a reference for studies of age-related lung diseases.