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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 Funding Opportunity Announcement (FOA) is dedicated to the discovery of therapeutic Biotechnology Products and Biologics (e.g., peptides, proteins, oligonucleotides, gene therapies, and cell therapies) for disorders that fall under the NINDS mission. It supports the optimization of therapeutic lead(s) showing convincing proof-of-concept. At the end of the funding period, projects that successfully advance through support from this program will have identified a optimized candidate, which has sufficient bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and/or target engagement, and other favorable properties that are consistent with the desired clinical application, and will be ready for entry into the CREATE Bio Development track for further development to enable filing for an Investigational New Drug (IND).

The purpose of this funding opportunity announcement (FOA) is to encourage research grant applications that propose to develop or substantially modify existing cutting-edge tools that will advance prenatal and/or pediatric hydrocephalus research. The primary objective of this FOA is to remove barriers to hydrocephalus research that are due to scarcity of tools to investigate both the disease mechanisms and alternative therapies (non-shunt) in a rigorous manner. Applications should aim to transform the field of prenatal and/or pediatric hydrocephalus research by generating tools including animal and cell models, novel methods and innovative technologies that will be widely used throughout the neuroscience community to understand disease mechanisms and/or developing therapeutics.

The purpose of this FOA is to promote the integration of experimental, analytic, and theoretical capabilities for large-scale analysis of neural systems and circuits. This FOA seeks applications for exploratory research studies that use new and emerging methods for large scale recording and manipulation of neural circuits across multiple brain regions. Applications should propose to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications should seek to understand circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Studies should incorporate rich information on cell-types, on circuit functionality and connectivity, and should be performed in conjunction with sophisticated analysis of complex, ethologically relevant behaviors. Applications should propose teams of investigators that seek to cross boundaries of interdisciplinary collaboration by bridging fields and linking theory and data analysis to experimental design. Exploratory studies supported by this FOA are intended to develop experimental capabilities and quantitative, theoretical frameworks in preparation for a future competition for larger-scale, multi-component, Team-Research BRAIN Circuit Programs (U19).

The purpose of this Funding Opportunity Announcement (FOA) is to support high risk/high reward research on the blood/vascular component and regulation of the neurovascular-blood unit (a.k.a., Blood-Brain Barrier; BBB) in normal and pathological states to create enhanced/modified platforms that more closely model the human BBB. Research addressing vascular, hemostatic, hematopoietic, and/or immune cell interaction across the Blood-Brain Interface is of particular interest. This initiative will serve to stimulate the development of a new field of science and re-define the neurovascular unit to also include the blood/vascular component to develop the next generation of pre-clinical human cellular model systems of the human BBB to complement research currently based on animal models.

This Funding Opportunity Announcement (FOA) enables data-driven drug repositioning and combination therapy for Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) by developing computational methods and data resources and/or integrating computational approaches with proof-of-concept efficacy studies in cell-based models, animal models, and/or humans.

The goal of the K12 Institutional Career Development Program in HIV-related Heart, Lung, Blood, and Sleep (HLBS) research is to encourage institutions to develop and sustain programs that support inter-disciplinary, intensive mentored research training and career development for junior PhDs and MDs in AIDS co-morbidities as well as cell and gene therapies for HIV cure and prevention of HIV transfusion transmission.

The purpose of this FOA is to promote the integration of experimental, analytic, and theoretical capabilities for large-scale analysis of neural systems and circuits. This FOA seeks applications for exploratory research studies that use new and emerging methods for large scale recording and manipulation of neural circuits across multiple brain regions. Applications should propose to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications should seek to understand circuits of the central nervous system by systematically controlling stimuli and/or behavior while actively recording and/or manipulating relevant dynamic patterns of neural activity and by measuring the resulting behaviors and/or perceptions. Studies should incorporate rich information on cell-types, on circuit functionality and connectivity, and should be performed in conjunction with sophisticated analysis of complex, ethologically relevant behaviors. Applications should propose teams of investigators that seek to cross boundaries of interdisciplinary collaboration by bridging fields and linking theory and data analysis to experimental design. Exploratory studies supported by this FOA are intended to develop experimental capabilities and quantitative, theoretical frameworks in preparation for a future competition for larger-scale, multi-component, Team-Research Circuit Programs (U19) awards.

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.

This funding opportunity (FOA) encourages small business technology transfer STTR research and development of commercial pharmaceutical interventions to extend lifespan and/or healthspan, to prevent, treat, and/or slow the progression of symptoms associated with Alzheimer's disease (AD) or Alzheimer's disease related dementia (ADRD) in human cells and/or tissue, in-vitro models, and/or non-human animals.

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative 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 and prevent brain disorders.

This Funding Opportunity Announcement (FOA) supports the development of therapeutic Biotechnology Products and Biologics (e.g., peptides, proteins, oligonucleotides, gene therapies, cell therapies, and novel emerging therapies) for disorders identified under the NINDS mission. An identified clinical candidate with sufficient bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and/or target engagement, and other favorable properties that are consistent with the desired clinical application, is required for entry to this CREATE Bio Development Track. Therefore, this FOA supports Investigational New Drug (IND)-enabling studies for a therapeutic candidate and the inclusion of an optional small delayed-onset first in human Phase I clinical trial. At the end of the funding period, a successful project should have at least an IND application submitted to the U.S. Food and Drug Administration (FDA). Also listed under U01.

The ADDF seeks to support comparative effectiveness research, prevention clinical trials, and epidemiological studies that probe whether the use or choice of drugs alters the risk for dementia or cognitive decline. Specifically, the Prevention Beyond the Pipeline RFP supports: * Studies Leveraging the Consortium of Cohorts for Alzheimer's Prevention Action (CAPA) * Comparative Effectiveness Research: Methods may include randomized trials or epidemiology. * Studies of Cognitive Decline and Cognitive Reserve: Methods may include epidemiology or clinical trials. Current target areas of interest include: - Epigenetics - Inflammation - Mitochondria & metabolic function - Neuroprotection - Proteostasis - Synaptic activity and neurotransmitters - Vascular function - Other aging targets (e.g. senescent cells) - Other novel targets or pathways that are supported by compelling evidence demonstrating a rational biological connection to age-related cognitive decline or dementia risk   

What: Awards a young scientist for the most outstanding neurobiological research based on methods of molecular and cell biology conducted by them during the past three years Who should apply: Neurobiologists who are under 35 and received their advanced degree within the past 10 years

"This Funding Opportunity Announcement (FOA) encourages research on the biology of high confidence risk factors associated with complex brain disorders, with a focus on the intracellular, transcellular and circuit substrates of neural function. For the purposes of this FOA, the term "complex" can refer to a multifactorial contribution to risk (e.g., polygenic and/or environmental) and/or highly distributed functional features of the brain disorder. Studies may be either hypothesis-generating (unbiased discovery) or hypothesis-testing in design and may utilize in vivo, in situ, or in vitro experimental paradigms, e.g., model organisms or human cell-based assays. While behavioral paradigms and outcome measures can be incorporated into the research design to facilitate the characterization of intracellular, transcellular and circuit mechanisms, these are neither required nor expected. Studies should not attempt to "model" disorders but instead should aim to elucidate the neurobiological impact of individual or combined risk factor(s), such as the affected molecular and cellular components and their relationships within defined biological process(es). This can include the fundamental biology of these factors, components and processes. The resulting paradigms, component pathways and biological processes should be disseminated with sufficient detail to enrich common and/or federated data resources (e.g., those contributing to the Gene Ontology, Synaptic Gene Ontology, FAIR Data Informatics) in order to bridge the gap between disease risk factors, biological mechanism and therapeutic target identification. The present announcement (R21 activity code) can be used for applications to develop early stage, high-risk, exploratory approaches or establish proof-of-concept where there is little or no preliminary data."

The purpose of this Funding Opportunity Announcement (FOA) is to support investigators who have interest and capability to join efforts for the discovery of in vivo chemical probes for novel brain targets. It is expected that applicants will have, in hand, the starting compounds ("validated hits") for chemical optimization and bioassays for testing new analog compounds. Through this FOA, NIH wishes to stimulate research in 1) discovery and development of novel, small molecules for their potential use in understanding biological processes relevant to the missions of NIMH, NIDA, NEI, and/or NIA and 2) discovery and/or validation of novel, biological targets that will inform studies of brain disease mechanisms. Emphasis will be placed on projects that provide new insight into important disease-related biological targets and biological processes. The main emphasis of projects submitted under this FOA should be the discovery of in vivo chemical probes. Applicants interested in developing cell-based chemical probes may wish to apply using the companion R21 mechanism, (PAR-21-028).

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.

This Funding Opportunity Announcement (FOA) encourages research grant applications directed toward the discovery of the impact of alterations associated with complex brain disorders on the fundamental cellular and molecular substrates of neuronal function. The present announcement seeks R01 applications. ALSO listed (R21)