BRAIN Initiative: Development of Novel Tools to Probe Cell-Specific and Circuit-Specific Processes in Human and Non-Human Primate Brain (UG3/UH3 Clinical Trial Optional)
This FOA is designed to support development and validation of novel tools to facilitate the detailed analysis and/or manipulation of cells and circuits and provide insights into the neural circuitry and structure underlying complex behaviors in humans and non-human primates and other mammalian brains (e.g., sheep, pig). The human brain consists of an estimated one hundred billion neurons and similar number of supporting glial cells that are uniquely organized to confer the extraordinary computational activities of the brain. Considerable progress has been made in defining the cytology and signal transduction processes in the CNS, but circuit-level function and the neural mechanisms of cognition and behavior remain poorly understood. Cell-type and circuit-specific manipulation strategies are key technical factors in addressing these important areas and represent attractive strategies to treat brain disorders. This initiative is focused on developing tools (or vastly improving existing tools) that will ultimately enable anatomical mapping, activity monitoring, and/or functional manipulation of individual cells and defined groups of cells within neuronal circuits of the human brain. In order to achieve these goals, the use of large brains such as those of non-human primates, sheep and pigs will be instrumental in this process. Development of tools that are applicable to human or non-human primate brains should focus on overcoming barriers to the use of such tools (e.g., opto/chemo and sonogenetic actuators). The tools sought through this FOA can include highly novel genetic or non-genetic methods for targeted delivery of genes, proteins, and chemicals to specific cells or tightly defined cell types and circuits.
Development of novel tools that will delineate anatomical connections between cells and expand our knowledge of circuit architecture and function is an area well poised for additional investment. Recently developed technologies (e.g., hydrogel-based brain tissue clearing, expansion microscopy, spatial transcriptomics, and several other imaging breakthroughs) allow an unprecedented three-dimensional view into the post-mortem brain. These exciting technologies hold promise for mapping short- and long-range connections throughout the brain. Coupled with improved activity monitoring technologies in awake, behaving animals, these new tools promise an understanding of circuitry in action. Further development of these technologies is crucial to push the envelope beyond our current capabilities. To this end, applicants from the biological sciences are encouraged to establish collaborations with engineers, chemists, material scientists, nanobiologists, and colleagues in other disciplines to develop groundbreaking approaches to study brain structure and activity.
This FOA aims to develop next-generation, innovative technologies to define, monitor, and/or modulate specific cell types in the large mammalian and non-human primate brain. Of high importance are first-in-class and/or cross-cutting non-invasive or minimally invasive techniques that permit repeated measurements from and manipulations of cells over time in a non-destructive manner.
Awards:
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Letter of Intent:
30 days prior to the application due date
Full Proposal Submission Deadline:
June 07, 2022
Contacts:
Douglas S. Kim, Ph.D., National Institute of Mental Health (NIMH), Telephone: 301-827-6463
Email: douglas.kim@nih.gov