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The NINDS, with other NIH Institutes and Centers participating in the BRAIN Initiative, intends to publish "BRAIN Initiative Advanced Postdoctoral Career Transition Award to Promote Diversity (K99/R00)." The program is designed to increase biomedical research workforce diversity and foster a strong cohort of new, highly skilled and well trained, NIH-supported, independent investigators from underrepresented groups working in research areas supported by the BRAIN Initiative, as highlighted in BRAIN 2025: A Scientific Vision. It is designed to facilitate a timely transition of outstanding postdoctoral researchers with a research and/or clinical doctorate degree from mentored, postdoctoral research positions to independent, tenure-track or equivalent faculty positions. This Notice is being provided to allow potential applicants sufficient time to develop meaningful mentoring teams and responsive projects. The FOA is expected to be published in April 2018 with an expected application due date in June 2018. This FOA will utilize the K99/R00 funding activity. Details of the planned FOA are provided below. Research Initiative Details The BRAIN Initiative K99/R00 award is intended for women and members of underrepresented groups who are working in research areas supported by the BRAIN Initiative, who have no more than five years of postdoctoral research experience, and who require at least 12 months of mentored research training and career development (K99 phase) before transitioning to the independent research (R00) phase of the program.

This funding opportunity announcement (FOA) invites applications for mentored career enhancement (K18) awards in research areas that are highly relevant to the NIH BRAIN Initiative. This career enhancement program will support development of research capability for the BRAIN Initiative, with specific emphasis on cross-training independent investigators in a substantively different area of neuroscience, neuroethics, or in a quantitative and physical discipline (e.g., physics, chemistry, engineering, computer science, mathematics); and vice versa, cross-training independent investigators trained in a quantitative or physical discipline proposing to gain in-depth training in a high-priority area of neuroscience. The research project conducted under this K18 should enhance the candidate's ability to significantly contribute to or lead projects that investigate questions central to the goals of the BRAIN Initiative. Eligible candidates are independent investigators at any faculty rank or level.

This funding opportunity announcement (FOA) invites applications for mentored career enhancement (K18) awards in research areas that are highly relevant to the NIH BRAIN Initiative. This career enhancement program will support development of research capability for the BRAIN Initiative, with specific emphasis on cross-training independent investigators in a substantively different area of neuroscience, neuroethics, or in a quantitative and physical discipline (e.g., physics, chemistry, engineering, computer science, mathematics); and vice versa, cross-training independent investigators trained in a quantitative or physical discipline proposing to gain in-depth training in a high-priority area of neuroscience. The research project conducted under this K18 should enhance the candidate's ability to significantly contribute to or lead projects that investigate questions central to the goals of the BRAIN Initiative. Eligible candidates are independent investigators at any faculty rank or level.

The purpose of this Funding Opportunity Announcement [FOA] submitted through the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is to stimulate the development and validation of novel tools and analytical methods to target, identify and characterize non-neuronal cells in the brain. This FOA complements previous and ongoing cell-census and tool development efforts initiated under BRAIN, RFA-MH-14-215 and RFA-MH-14-216, that have focused almost exclusively on neuronal cells. The cutting-edge tools and methods developed under this opportunity should focus specifically on providing improved points of entry into non-neuronal cell-types (glial and vascular) to enable their inventory and characterization within the CNS and help define how these cells interact among each other and with neuronal cells to impact functional circuitries. Plans for validating the utility of the tool/technology/method and demonstrating its advantage over currently available approaches will be an essential feature of a successful application. Tools that can be used in several species or model organisms rather than in a single species are especially desirable.

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.

The purpose of the BRAIN Initiative Fellows (F32) program is to enhance the research training of promising postdoctorates, early in their postdoctoral training period, who have the potential to become productive investigators in research areas that will advance the goals of the BRAIN Initiative. Applications are encouraged in any research area that is aligned with the BRAIN Initiative, including neuroethics. Applicants are expected to propose research training in an area that complements their predoctoral research. Formal training in quantitative perspectives and analytical tools is expected to be an integral part of the proposed research training plan. In order to maximize the training potential of the F32 award, this program encourages applications from individuals who have not yet completed their terminal doctoral degree and who expect to do so within 12 months of the application due date. On the application due date, candidates may not have completed more than 6 months of postdoctoral training.  

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.

This funding opportunity announcement (FOA) supports efforts to disseminate resources and to integrate them into neuroscience research practice. Projects should be highly relevant to specific goals of the BRAIN Initiative, goals that are described in the planning document "BRAIN 2025: A Scientific Vision." They should engage in one or more of the following activities: distribution of tools and reagents; user training on the usage of new technologies or techniques; providing access to existing technology platforms and specialized facilities; minor improvements to increase the scale/efficiency of resource production and delivery; minor adaptations to meet the needs of a user community. Applications strictly focused on technology or software development, rather than dissemination of an existing resource, are not responsive to this FOA. Refinements to microscopes or tools necessary to customize them to the experimental needs of the end users are allowed. Projects should address compelling needs of neuroscience researchers working toward the goals of the BRAIN 2025 report that are otherwise unavailable or impractical in their current form.

The McKnight Endowment Fund for Neuroscience supports innovative research designed to bring science closer to the day when diseases of the brain can be accurately diagnosed, prevented, and treated. To that end, the McKnight Endowment Fund for Neuroscience invites Letters of Intent for its 2018 McKnight Technological Innovations in Neuroscience awards. The program encourages and supports scientists working on the development of novel and creative approaches to the understanding of brain function. McKnight is interested in 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. A goal of the Technological Innovations awards is to foster collaboration between the neurosciences and other disciplines; therefore, collaborative and cross-disciplinary applications are explicitly invited.

This Funding Opportunity Announcement (FOA) encourages exploratory/developmental grant (R21) applications from institutions and organizations that propose to study the effects and functional consequences of cannabis and cannabinoid exposures on the developing brain, from pre-, peri-, post-natal development through young adulthood in animal models and humans. Topics of interest pertaining to this PA include, but are not limited to: molecular and cellular mechanisms of cannabis/cannabinoid effects on the developing brain; long term functional consequences of cannabis/cannabinoid exposure on learning and memory, cognitive and emotional development. 

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 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.

Understanding the dynamic activity of neural circuits is central to the NIH BRAIN Initiative. This FOA seeks applications for proof-of-concept testing and development of new technologies and novel approaches for largescale recording and manipulation of neural activity to enable transformative understanding of dynamic signaling in the nervous system. In particular, we seek exceptionally creative approaches to address major challenges associated with recording and manipulating neural activity, at or near cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain. It is expected that the proposed research may be high-risk, but if successful could profoundly change the course of neuroscience research. 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. Where appropriate, applications are expected to integrate appropriate domains of expertise, including biological, chemical and physical sciences, engineering, computational modeling and statistical analysis.

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).

HIV-associated neurological disorders (HAND) persist in up to 50% of HIV-patients even when HIV replication is suppressed by combination antiretroviral therapy (cART), which transformed HIV/AIDS from a fatal illness into a chronically managed long-term condition. HIV does not infect neurons, but infects microglia and macrophages in the brain, causing HAND associated neuropathology. HAND epitomizes a series of disorders include Asymptomatic Neurocognitive Impairment (ANI), Mild Neurocognitive Disorder (MND), and HIV-Associated Dementia (HAD). These neurocognitive deficits interfere with psychomotor speed and coordination, diminishing memory and executive functions, and reduce quality of life in long-standing aviremic HIV-positive patients. These clinical challenges mandate research for a better understanding of HIV neuropathology; however, currently there are no effective approaches for HIV-infected live human brain studies or realistic HIV-infected animal models for HIV neuropathology. Proposed projects MUST include the following components. Applications which lack these three components will be considered non-responsive to the FOA and will not be reviewed. The major thrust of the project MUST involve exploitation of induced microglia and cerebral organoids generated from patient derived iPSC lines to better understand the molecular and cellular mechanisms of HIV-Associated Neurocognitive Disorder (HAND). At least one aim or sub-aim MUST also involve either 1. opioid, cannabinoid, methamphetamine, nicotinic, dopaminergic, or other signaling pathways relevant to addictive substance use, or 2. exposure to addictive substances, or 3. analysis of samples from patients that have used addictive substances or have SUDs.

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.

This FOA invites applications that apply a cross-disciplinary, team science approach to gain comprehensive, mechanistic understanding of the impact of sex differences on the trajectories of brain aging and phenotypes of AD risk and on the responsiveness to pharmacologic and non-pharmacologic interventions.  

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.

This funding opportunity announcement (FOA) supports the development of PET radioligands that identify proteinopathies or pathological processes associated with the human biology of Alzheimer's disease related dementias (ADRDs). Activities supported under this FOA include, but are not limited to the in vitro screening of existing ligands against human ADRD brain tissue, medicinal chemistry support for development of new compounds and improvement of existing ligand specificity and selectivity, initial screening of ligands in appropriate animal models, and radioligand formulation and first-in-human testing. The Center without Walls should encompass research that will move promising ligands through in vitro and in vivo optimization to first-in-human studies. Applications must include an administrative core, a medicinal chemistry core, a clinical core, a scientific governance structure, and a minimum of two research projects with milestone plans that address workflows for screening of existing and newly derived ligands against human ADRD tissue and appropriate animal models. Synergy must be evident among Center research projects and cores, such that successful completion of the aims could not be accomplished without the Center structure.

The goal of this funding opportunity announcement is to continue and expand the open-science, systems-biology enterprise of the AMP-AD Target Discovery and Preclinical Validation Consortium and enable data-driven discovery and validation of novel targets and biomarkers for AD and AD-related dementias through the development of predictive network models of brain health and disease.

The purpose of this Funding Opportunity Announcement (FOA) is to accelerate the discovery and development of medications to treat Cannabis Use Disorders (CUDs) using the UG3/UH3 mechanism. The objective is to advance medications toward the ultimate goal of obtaining FDA approval. Advances in understanding the cannabinoid systems and the effects of marijuana on the brain, coupled with the availability of both novel and marketed medications that may be efficacious to treat these disorders, offer unprecedented opportunities to develop safe and effective pharmacotherapies for CUDs. The compounds to be evaluated can be small molecules or biologics. They can be tested in pre-clinical models and/or for the clinical manifestations of CUDs or their consequences such as withdrawal, craving, or cannabis use relapse. Applications may focus on the development of new chemical entities, new formulations of marketed medications available for other indications, or combinations of medications that hold promise for the treatment of CUDs. The UG3/UH3 Phase Innovation Awards Cooperative Agreement involves 2 phases. The UG3 is to support a project with specific milestones to be accomplished by the end of the 2-year period. The UH3 is to provide funding for 3 years to a project that successfully completed the milestones set in the UG3. UG3 projects that have met their milestones will be administratively considered by NIDA and prioritized for transition to the UH3 phase. Investigators responding to this FOA must address both UG3 and UH3 phases.