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The purpose of this Funding Opportunity Announcement (FOA) is to invite applications (via limited competition) for SPARC Comprehensive Functional Mapping of Neuroanatomy and Neurobiology of Organs. These projects will comprehensively provide data for developing detailed, predictive functional and anatomical neural circuit maps for neural control of major functions of organs and their functionally-associated structures. 

The goal of this FOA is to advance research on the underlying basis for the transfer (or transposition) of aging phenotypes observed between young and old rodents and discovered through heterochronic parabiosis. Examples of transposed phenotypes include reversal of cardiac hypertrophy, partial restoration of cognitive function, improved vascularization, and repair of skeletal muscle after cryo-injury (anti-geronic transposition), or as accelerated loss of cognitive function and neurogenesis (pro-geronic transposition). Other transposed phenotypes, as revealed solely through heterochronic parabiosis, may also be reported in the literature. There are also reports of candidate factors found in circulation that might be causally related to the transposition of these aging phenotypes; these are termed "circulating geronic factors" for purposes of this FOA. To date, these are proteins and peptides that pass between the young and old mice joined by parabiosis, due to anastomosis of their circulatory systems. Based on these novel findings and this novel experimental paradigm, the specific objective of this FOA is to test whether these candidate geronic factors are necessary for the transposition of aging phenotypes. The focus is on phenotypes transposed in heterochronic parabiosis and the candidate factors which are present and functional at physiological concentrations in circulation.

The goal of this FOA is to advance research on the underlying basis for the transfer (or transposition) of aging phenotypes observed between young and old rodents and discovered through heterochronic parabiosis. Examples of transposed phenotypes include reversal of cardiac hypertrophy, partial restoration of cognitive function, improved vascularization, and repair of skeletal muscle after cryo-injury (anti-geronic transposition), or as accelerated loss of cognitive function and neurogenesis (pro-geronic transposition). Other transposed phenotypes, as revealed solely through heterochronic parabiosis, may also be reported in the literature. There are also reports of candidate factors found in circulation that might be causally related to the transposition of these aging phenotypes; these are termed "circulating geronic factors" for purposes of this FOA. To date, these are proteins and peptides that pass between the young and old mice joined by parabiosis, due to anastomosis of their circulatory systems. Based on these novel findings and this novel experimental paradigm, the specific objective of this FOA is to test whether these candidate geronic factors are necessary for the transposition of aging phenotypes. The focus is on phenotypes transposed in heterochronic parabiosis and the candidate factors which are present and functional at physiological concentrations in circulation.

Professional services are required to develop and evaluate techniques for analyzing anatomical and functional brain data using deformable shape and appearance volume models (Metamorphs/Active Volume Models), stretching open active contours (SOAX), and advanced classification methods, including deep learning.  These methods will be investigated and state-of-the-art tools developed for the segmentation of brain MRI and diffusion imaging data and the analysis of fMRI data, with the aim of supporting research into understanding functional brain circuits and their anatomical correlations. Functional-anatomical atlases will be developed to facilitate comparisons across individuals and for statistical modeling.  The required work is projected to be a multi-year effort, with the first year concentrating on feasibility and prototype development.  Subsequent two-year work, if justified by first-year results, will concentrate on the  development and further evaluation of the prototypes as mature tools that contribute to the wider national research initiative to accurately model functioning of the human brain.

Repeated exposure to drugs of abuse can cause changes in neuronal structure and function that contribute to and sustain drug use. Research has largely focused on the interactions of drugs with specific neuronal targets, and on the consequences of drug exposure on neuronal function, excitability, neuroplasticity, and neurochemistry. However, emerging evidence shows that neuroimmune factors, released from both glia or neurons, can modulate neuronal structure and function, either by affecting neuron-glia interactions or through direct effects on neurons. Yet the role of neuroimmune signaling in the modulation of neuronal function as it affects the expression of substance use behaviors is poorly understood. Research has shown that drugs of abuse, including methamphetamine, morphine, cocaine and nicotine, can elicit neuroinflammatory responses. Stress, an important contributor to relapse, can also elicit neuroimmune responses. Consequently, neuroimmune signaling may be integral to mechanisms underlying drug misuse, addiction, and other consequences of repeated drug use. Further, because the molecular targets and receptors for abused substances differ, the complement of neuroimmune factors affected by exposure to a particular drug may be drug-specific. Research to identify the commonalities between specific drugs of abuse, the neuroimmune factors released by drug use, and the neuroanatomical specificity of the responses is needed. It is expected that the contributing actions of neuroimmune signaling to addictive behaviors are most likely due not to obvious brain damage and overt pathology, but to the consequences of such signaling in altering specific molecular and cellular processes within glia, neurons, and neural circuits.

This Funding Opportunity Announcement (FOA) encourages Exploratory/Developmental Research Project Grant (R21) applications from institutions/organizations that propose to study the neuroimmune mechanisms of alcohol related disorders. Studies using animal models and post-mortem human alcoholic brains suggest that alcohol exposure alters the neuroimmune system in the brain. However, it remains unclear how the altered neuroimmune signaling contributes to brain functional and behavioral changes associated with alcohol dependence. Recent studies reveal that neuroimmune molecules are expressed in neurons and glia, and play an important role in modulating synaptic function, neurodevelopment, and neuroendocrine function. These neuromodulatory properties, together with their essential roles in neuroinflammation, provide a new frame work to understand the role of neuroimmune factors in mediating neuroadaptation and behavioral phenotypes associated with alcohol use disorders. Studies supported by this FOA will provide fundamental insights of neuroimmune mechanisms underlying brain functional and behavioral changes induced by alcohol.

This Funding Opportunity Announcement (FOA) encourages Exploratory/Developmental Research Project Grant (R21) applications from institutions/organizations that propose to study the neuroimmune mechanisms of alcohol related disorders. Studies using animal models and post-mortem human alcoholic brains suggest that alcohol exposure alters the neuroimmune system in the brain. However, it remains unclear how the altered neuroimmune signaling contributes to brain functional and behavioral changes associated with alcohol dependence. Recent studies reveal that neuroimmune molecules are expressed in neurons and glia, and play an important role in modulating synaptic function, neurodevelopment, and neuroendocrine function. These neuromodulatory properties, together with their essential roles in neuroinflammation, provide a new frame work to understand the role of neuroimmune factors in mediating neuroadaptation and behavioral phenotypes associated with alcohol use disorders. Studies supported by this FOA will provide fundamental insights of neuroimmune mechanisms underlying brain functional and behavioral changes induced by alcohol.

This Funding Opportunity Announcement (FOA) encourages Exploratory/Developmental Research Project Grant (R21) applications from institutions/organizations that propose to study the neuroimmune mechanisms of alcohol related disorders. Studies using animal models and post-mortem human alcoholic brains suggest that alcohol exposure alters the neuroimmune system in the brain. However, it remains unclear how the altered neuroimmune signaling contributes to brain functional and behavioral changes associated with alcohol dependence. Recent studies reveal that neuroimmune molecules are expressed in neurons and glia, and play an important role in modulating synaptic function, neurodevelopment, and neuroendocrine function. These neuromodulatory properties, together with their essential roles in neuroinflammation, provide a new frame work to understand the role of neuroimmune factors in mediating neuroadaptation and behavioral phenotypes associated with alcohol use disorders. Studies supported by this FOA will provide fundamental insights of neuroimmune mechanisms underlying brain functional and behavioral changes induced by alcohol.

This FOA encourages Research Project Grant (R01) applications from institutions/organizations that propose to study the neuroimmune mechanisms of alcohol-related disorders. Studies using animal models and post-mortem human alcoholic brains suggest that alcohol exposure alters the neuroimmune system in the brain. However, it remains unclear how the altered neuroimmune signaling contributes to brain functional and behavioral changes associated with alcohol dependence. Recent studies reveal that neuroimmune molecules are expressed in neurons and glia, and play an important role in modulating synaptic function, neurodevelopment, and neuroendocrine function. These neuromodulatory properties, together with their essential roles in neuroinflammation, provide a new frame work to understand the role of neuroimmune factors in mediating neuroadaptation and behavioral phenotypes associated with alcohol use disorders. Studies supported by this FOA will provide fundamental insights of neuroimmune mechanisms underlying brain functional and behavioral changes induced by alcohol. 

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is aimed at revolutionizing neuroscience through development and application of innovative technologies to map neural circuits, monitor and modulate their activity, and understand how they contribute to thoughts, sensations, emotions and behavior. NIH has issued a variety of Funding Opportunity Announcements (FOAs) that will support projects that apply technologies to understand neural circuit function in the context of specific circuits, resulting in a diverse portfolio of research into the fundamental biology of nervous system function. The purpose of this announcement is to notify the research community that NIH welcomes BRAIN Initiative applications targeting central nervous system nociceptive and pain circuits, as appropriate to the goals and requirements of specific BRAIN Initiative FOAs. Pain conditions represent an important public health problem and NIH continues to support research into pain pathologies through normal Institute and Center appropriations. However, pain and nociception are also components of normal nervous system function, and the BRAIN Initiative is committed to understanding pain circuits along with brain circuits underlying other sensory, motor, cognitive and emotional functions. It is expected that the unique opportunities of the BRAIN Initiative will enable production of detailed maps of pain circuits, and the adoption of powerful new tools for monitoring and modulating pain circuit activity, leading to significant advances in the understanding of pain and nociception. For a list of past and open BRAIN Initiative FOAs, see https://braininitiative.nih.gov/funding/.

This NIH Funding Opportunity Announcement (FOA) is part of the Stimulating Peripheral Activity to Relieve Conditions (SPARC) Common Fund program. This FOA solicits applications for support of research to gather critical data and answer critical questions on functional peripheral neuroanatomy of organs and reveal the organ function controlled by neural circuits.   Organs of interest include those where the peripheral neuroanatomy and functional neurobiology of the organ have been understudied, and which are not the subject of existing SPARC funding under RFA-RM-15-018 (see below).  

The goal of this FOA is to transform our understanding of how dynamic interactions among multiple cell types involved in neuroimmune interactions (e.g., neurons, glia cells, neurovascular units, or other neuroimmune components) mediate the transition from normal central nervous system (CNS) function to disorder conditions. Previous findings have markedly advanced our knowledge of neuroimmune interactions during normal brain function, neurodevelopment, and in the context of established diseases. However, there is a lack of understanding of how multiple neuroimmune components mediate transitions from normal brain function to the early stages of CNS disorders, how changes in immune signaling are integrated into neuronal networks, and how disease progression is orchestrated by multiple neuroimmune components. With this FOA, we encourage projects that combine diverse expertise and use innovative approaches to address these questions at the molecular, cellular, and circuitry levels. The outcomes of this research will provide an integrated view of the dynamic changes among multiple neuroimmune components and how they contribute to the onset and progression of CNS disorders.

The Encyclopedia of DNA Elements (ENCODE) project, by systematically cataloging transcribed regions, transcription factor binding sites, and chromatin structure, has recently found that a larger fraction of the human genome may be functional than was previously appreciated. However, our understanding of the role of these functional genomic elements in neurodevelopment and mental disorders is at an early stage. This funding opportunity will support studies that identify non-coding functional genomic elements and elucidate their role in the etiology of mental disorders.

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 Division of Integrative Organismal Systems (IOS) supports research aimed at understanding why organisms are structured the way they are and function as they do. Proposals should focus on organisms as a fundamental unit of biological organization. Principal Investigators (PIs) are encouraged to apply systems approaches that will lead to conceptual and theoretical insights and predictions about emergent organismal properties. Areas of inquiry include, but are not limited to, developmental biology and the evolution of developmental processes, nervous system development, structure, and function, physiological processes, functional morphology, symbioses, interactions of organisms with biotic and abiotic environments, and animal behavior.

Studies funded by our Basic Research RFP will fall into one the following key areas, which are listed in random order: 1. Studies focused on the molecular and biochemical mechanisms regulating SMN expression or mediating SMN function. Results should lead to a better understanding of the requirements for SMN protein biologically, informing therapy development. Such studies may also identify genetic modifiers, upstream regulators of SMN expression / splicing / function, and downstream effectors of SMN functional activity, resulting in novel drug targets.      2.  Studies resulting in greater understanding of the pathophysiology of SMA, using well-validated animal or cellular models of the SMA. This includes focus on the tissue requirements for SMN protein, clarifying the cellular autonomy of the disease in motor neurons and other cells, peripheral versus central manifestations of the disease, and other areas.  3. Early proof-of concept assessment of novel therapeutic approaches for SMA in well-validated animal or cellular models of the disease. 4. Work focused on generating research and clinical trial tools, such as new animal models for SMA, phenotypic cellular assays for SMA, biomarkers or outcome measures for SMA clinical trials, newborn screening protocols, and others.

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.

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.

These awards encourage and support scientists working on the development of novel and creative approaches to understanding brain function. The fund supports efforts to examine how a new technology may be used to monitor, manipulate, analyze, or model brain function at any level, from the molecular to the entire organism. Technology may take any form, from biochemical tools to instruments to software and mathematical approaches. Because the program seeks to advance and enlarge the range of technologies available to the neurosciences, research based primarily on existing techniques will not be considered.

These awards encourage and support scientists working on the development of novel and creative approaches to understanding brain function. The fund supports efforts to examine how a new technology may be used to monitor, manipulate, analyze, or model brain function at any level, from the molecular to the entire organism. Technology may take any form, from biochemical tools to instruments to software and mathematical approaches. Because the program seeks to advance and enlarge the range of technologies available to the neurosciences, research based primarily on existing techniques will not be considered.

The purpose of this FOA is to invite applications that investigate aspects of lymphatic vessel physiology, development and pathophysiology related to health and diseases of the digestive system. Studies to understand the factors that control local lymphatic vessel functional anatomy and physiology and development during health or disease in this system and its organs, and the mechanisms by which alterations of lymphatic vessel function affect organ function, are of interest. However, studies with the major focus on immune mechanisms, role of lymphatics in cancer metastasis and study of lymphatic vessels in organs other than those from the digestive system will not be considered responsive.