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This Funding Opportunity Announcement (FOA) intends to support investigators who have interest and capability to join efforts for the discovery of cell-based 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, NIA, and/or NIDCD; 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 in the discovery of cell-based chemical probes. Applicants interested in developing in vivo chemical probes may wish to apply using the companion R01 mechanism (PAR-17-336).

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).

This Funding Opportunity Announcement (FOA) intends 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.

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.

The Klarman Family Foundation is interested in providing strategic investment in translational research that will accelerate progress in developing effective treatments for anorexia nervosa, bulimia nervosa and binge eating disorder. The Program's short-term goal is to support the most outstanding science and expand the pool of scientists whose research explores the basic biology of feeding, anorexia nervosa, bulimia nervosa, and/or binge eating disorder. The long-term goal is to improve the lives of patients suffering from these conditions. Examples of funding areas include but are not limited to molecular genetic analysis of relevant neural circuit assembly and function; genetic and epigenetic research; animal models created by genetically altering neural circuits; and testing of new chemical entities that might be used in animal models as exploratory treatments.  Please note that imaging studies involving humans are not eligible. Investigators conducting research in the neuro-circuitry of fear conditioning or reward behavior may also apply but must justify the relevance of their research projects to the basic biology of eating disorders. Clinical psychotherapeutic studies, medication trials and research in the medical complications of these disorders are outside the scope of this Program.

A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. While currently available technologies can provide some understanding, they may not be sufficient to accomplish this goal. For example, non-invasive technologies are low resolution and/or provide indirect measures such as blood flow, which are imprecise; invasive technologies can provide information at the level of single neurons producing the fundamental biophysical signals, but they can only be applied to tens or hundreds of neurons, out of a total number in the human brain estimated at 85 billion. Other BRAIN FOAs seek to develop novel technology (RFA-NS-16-006) or to optimize existing technology ready for in-vivo proof-of-concept testing and collection of preliminary data (RFA-NS-16-007) for recording or manipulating neural activity on a scale that is beyond what is currently possible. This FOA seeks applications for unique and innovative technologies that are in an even earlier stage of development than that sought in other FOAs, including new and untested ideas that are in the initial stages of conceptualization.

TRANSLATIONAL MEDICINE AND THERAPEUTICS: The goal of the PhRMA Foundation's Translational Medicine and Therapeutics Program is to promote the development and use of experimental and computational methods in an integrative approach towards clinical needs in diagnosis, treatment and prevention. This can involve enhanced understanding of human biological and disease processes but requires a strong translational component. This program will support the concepts of Translational Medicine and Therapeutics as defined by the Foundation: "Translational medicine and therapeutics is a discipline focused on bridging experimental and computational technologies and discoveries in the research laboratory to their application in clinical practice. Examples of research components include activities in molecular and cellular biology, pathophysiology, systems biology, bioinformatics, modeling and simulation, and other quantitative sciences to connect basic biological concepts and entities to directly address unmet medical needs. The goals are to use clinical observation as the basis for hypothesis generation to further basic research and to efficiently advance the product of basic research to patients." Translational Medicine and Therapeutics awards will advance training and support career development of scientists engaged in research that significantly integrates cutting-edge technologies with advanced biological, chemical, and pharmacological sciences and engineering methodologies in such areas as (but not restricted to): * Genetics (Molecular, Pharmaco-, Population, Medical) * Genomics (Functional, Structural, Toxico-, Pharmaco-, Comparative) * Systems (Biology and Pharmacology) * Pathways and networks * Integrative biology * Modeling and simulation * Target Identification and Validation * Biomarker Discovery and Validation * Vaccine Development * Molecular Epidimiology * Imaging * Disease Modeling

The "epitranscriptome" refers to chemical modifications of RNA molecules.  RNA modifications in the brain have been reported to regulate the fate and function of both coding and noncoding RNAs and are emerging as a critical element of cellular function. The purpose of this initiative is to stimulate research into the functions of modified RNAs in the brain and in the associated modification proteins that act on RNA (readers, writers, and erasers) that play a role in basic neurobiological and behavioral processes implicated in mental and substance use disorders.   

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 confer a high degree of cell-type and/or circuit-level specificity. Validation of the utility of the tool/technology is an essential feature. A particular emphasis for this funding opportunity announcement (FOA) is the development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest; new approaches are also expected to target specific cell types and or circuits in the nervous system with greater precision and sensitivity than currently established methods. Tools developed through this initiative 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 also encouraged.

The overall goal of this initiative is to identify, optimize, and evaluate measures of neurophysiological processes that are disrupted within or across mental disorders and which can be assessed in animals and humans. The goal is to support further development of these measures as assays for evaluating potential new drug and device therapies and their targets. Data will also reveal assay measures where the performance between preclinical species and humans is dissimilar, thus establishing a firm basis for limiting speculative extrapolations of preclinical findings. Ultimately, the goal of this FOA is to improve the efficiency of the therapeutic development process by addressing inconsistencies between the preclinical screening pipeline and clinical evaluation of new treatment candidates and thereby hasten the development of more effective treatments for mental disorders. The objectives of the FOA will be accomplished by supporting partnerships among basic and translational neuroscientists who are committed to advancing the discovery of physiological measures as tools for target validation and therapeutic development. Groups will be tasked with building a target-engagement-linked-to-functional-brain-effect suite of assays with potential to translate from animals to humans and thus serve as a basis for selecting preclinical treatment candidates for further development and clinical testing. Towards this goal, the FOA will support development, optimization and evaluation of brain based assays in both preclinical species and in healthy humans and the evaluation of assay performance in response to carefully selected chemical, physiological, or behavioral manipulations.

A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. Available technologies for recording and manipulating neural circuit activity in human and animal experiments are not sufficient to accomplish this goal. Non-invasive technologies are low resolution and/or provide indirect measures such as blood flow, which are imprecise. Invasive technologies can provide information at the level of single neurons producing the fundamental biophysical signals, but they can only be applied to tens or hundreds of neurons, out of a total number in the human brain estimated at 85 billion. Previous BRAIN FOAs sought to develop novel technology (RFA-NS-15-003) or to optimize existing technology ready for in-vivo proof-of-concept testing and collection of preliminary data (RFA-NS-15-004). This FOA seeks applications for technology at an even earlier stage of development. It seeks new and untested ideas that are in the very earliest stages. The support provided might enable calculations, simulations, computational models, or other mathematical approaches for demonstrating that the signal sources and/or measurement technologies are theoretically capable of meeting the demands of large-scale recording or manipulation of circuit activity. The support might also be used for building and testing phantoms, prototypes, in-vitro or other bench-top models in order to validate underlying theoretical assumptions in preparation for future FOAs aimed at testing in animal models. Invasive or non-invasive approaches are sought that will ultimately enable or reduce the current barriers to large-scale recording or manipulation of neural activity, and that would be compatible with experiments in humans or behaving animals. Applications are encouraged from any qualified individuals, including physicists, engineers, theoreticians, and scientists, especially those no

Understanding how behavior emerges from the dynamic patterns of electrical and chemical activity of brain circuits is universally recognized as one of the great, unsolved mysteries of science. Advances in recent decades have elucidated how individual elements of the nervous system and brain relate to specific behaviors and cognitive processes. However, there remains much to discover to attain a comprehensive understanding of how the healthy brain functions, specifically, the general principles underlying how cognition and behavior relate to the brain's structural organization and dynamic activities, how the brain interacts with its environment, and how brains maintain their functionality over time.

Understanding how behavior emerges from the dynamic patterns of electrical and chemical activity of brain circuits is universally recognized as one of the great, unsolved mysteries of science. Advances in recent decades have elucidated how individual elements of the nervous system and brain relate to specific behaviors and cognitive processes. However, there remains much to discover to attain a comprehensive understanding of how the healthy brain functions, specifically, the general principles underlying how cognition and behavior relate to the brain's structural organization and dynamic activities, how the brain interacts with its environment, and how brains maintain their functionality over time. Achieving an understanding of brain structure and function that spans levels of organization, spatial and temporal scales, and the diversity of species requires an international,transdisciplinary collaborative effort to not only integrate discipline-specific ideas andapproaches but also extend them to stimulate new discoveries, and innovativeconcepts, theories, and methodologies. The objective of this phase of the NeuroNex Program is the establishment of distributed, international research networks that build on existing globalinvestments in neurotechnologiesto address overarching questions in neuroscience. The creation of such global research networks of excellence will foster international cooperation by seeding close interactions between a wide array of organizations across the world, as well as creating links and articulating alliances between multiple recently launched international brain projects.

Understanding how behavior emerges from the dynamic patterns of electrical and chemical activity of brain circuits is universally recognized as one of the great, unsolved mysteries of science. Advances in recent decades have elucidated how individual elements of the nervous system and brain relate to specific behaviors and cognitive processes. However, there remains much to discover to attain a comprehensive understanding of how the healthy brain functions, specifically, the general principles underlying how cognition and behavior relate to the brain's structural organization and dynamic activities, how the brain interacts with its environment, and how brains maintain their functionality over time. Achieving an understanding of brain structure and function that spans levels of organization, spatial and temporal scales, and the diversity of species requires an international, transdisciplinary collaborative effort to not only integrate discipline-specific ideas and approaches but also extend them to stimulate new discoveries, and innovative concepts, theories, and methodologies.

Understanding the dynamic activity of neural circuits is central to the NIH BRAIN Initiative. Although invention and proof-of-concept testing of new technologies are a key component of the BRAIN Initiative, to achieve their potential these technologies must also be optimized through feedback from end-users in the context of the intended experimental use. This FOA seeks applications for the optimization of existing and emerging technologies and approaches that have potential to address major challenges associated with recording and manipulating neural activity, at or near cellular resolution, at multiple spatial and temporal scales, in any region and throughout the entire depth of the brain. This FOA is intended for the iterative refinement of emergent technologies and approaches that have already demonstrated their transformative potential through initial proof-of-concept testing, and are appropriate for accelerated development of hardware and software while scaling manufacturing techniques towards sustainable, broad dissemination and user-friendly incorporation into regular neuroscience practice. Proposed technologies should be compatible with experiments in behaving animals, and should include advancements that enable or reduce major barriers to hypothesis-driven experiments. Technologies may engage diverse types of signaling beyond neuronal electrical activity for large-scale analysis, and may utilize any modality such as optical, electrical, magnetic, acoustic or genetic recording/manipulation. Applications that seek to integrate multiple approaches are encouraged. Applications are expected to integrate appropriate domains of expertise, including where appropriate biological, chemical and physical sciences, engineering, computational modeling and statistical analysis. Also listed under R01

The Alzheimer's Drug Discovery Foundation has issued a Request for Proposals for its Preclinical Drug Discovery program. Through the program, grants of up to $600,000 over two years will be awarded to promising preclinical drug discovery programs relevant to Alzheimer's disease, related dementias, and cognitive aging. Preclinical research funding priorities include high throughput screening, medicinal chemistry hit-to-lead development and optimization, in vitro and in vivo efficacy studies, ADME, toxicology, pharma-cokinetics and pharma-co-dynamics, and in vivo proof-of-concept with lead compounds and biologics. Program areas of particular interest include new chemical compounds for Alzheimer's disease, preclinical proof-of-concept, and re-purposing. With regards to potential drug targets, ADDF is interested in novel targets that include but are not limited to neuro-inflammation, protein degradation/autophagy, growth factor signaling, synaptic function/morphology, calcium regulation, energy utilization/mitochondria function, insulin sensitivity, epigenetics, ApoE function and cholesterol metabolism, vascular injury and the blood-brain barrier interface, cognitive enhancers, myelin changes, ischemia and oxidative stress, and tau-related toxicities. To be eligible, applicants must be academic investigators seeking to create and support innovative translational programs in academic medical centers and universities; biotechnology companies with programs dedicated to Alzheimer's disease translational development; and new biotechnology company spinouts or existing biotechnology companies that demonstrate a clear need for nonprofit funding. Funding is provided through program-related investments (PRIs) that require a return on investment based on scientific and/or business milestones.

A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. While currently available technologies can provide some understanding, they may not be sufficient to accomplish this goal. For example, non-invasive technologies are low resolution and/or provide indirect measures such as blood flow, which are imprecise; invasive technologies can provide information at the level of single neurons producing the fundamental biophysical signals, but they can only be applied to tens or hundreds of neurons, out of a total number in the human brain estimated at 85 billion. Other BRAIN FOAs seek to develop novel technology (RFA-NS-17-003) or to optimize existing technology ready for in-vivo proof-of-concept testing and collection of preliminary data (RFA-NS-17-004) for recording or manipulating neural activity on a scale that is beyond what is currently possible. This FOA seeks applications for unique and innovative technologies that are in an even earlier stage of development than that sought in other FOAs, including new and untested ideas that are in the initial stages of conceptualization.

A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. While currently available technologies can provide some understanding, they may not be sufficient to accomplish this goal. For example, non-invasive technologies are low resolution and/or provide indirect measures such as blood flow, which are imprecise; invasive technologies can provide information at the level of single neurons producing the fundamental biophysical signals, but they can only be applied to tens or hundreds of neurons, out of a total number in the human brain estimated at 85 billion.

A central goal of the BRAIN Initiative is to understand how electrical and chemical signals code information in neural circuits and give rise to sensations, thoughts, emotions and actions. While currently available technologies can provide some understanding, they may not be sufficient to accomplish this goal. For example, non-invasive technologies are low resolution and/or provide indirect measures such as blood flow, which are imprecise; invasive technologies can provide information at the level of single neurons producing the fundamental biophysical signals, but they can only be applied to tens or hundreds of neurons, out of a total number in the human brain estimated at 85 billion.

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.