This FOA aims to address three major goals. The first is to utilize single-cell(-nuc) technologies to characterize the changes to cell identity, number, and/or morphology within a defined brain region, the hippocampus, from subjects experiencing mild cognitive impairment (MCI). Specifically, applicants will collect single-cell(-nuc) transcriptomic and epigenetic data from neuronal, glial, or vascular cells using MCI autopsy brains. Next, applicants will propose a data coordination center to collect single-cell(-nuc) omics data generated using diverse tissue sources and various, well-documented tissue preparation techniques from each group in the consortium. This data will be used to identify critical factors for robust and accurate single-cell(-nuc) omics analysis. Finally, this FOA will prompt applicants to coordinate their single-cell(-nuc) data sets with those produced by the BRAIN Initiatives human cell census. The aim is to enable investigators to utilize BRAIN cell census data sets generated from the analysis of healthy human brain and harmonize single-cell(-nuc) data sets from ADRD human brains with the BRAIN Initiative cell type registry.

More than 25 million Americans suffer from daily chronic pain, a highly debilitating medical condition that is complex and difficult to manage. In recent decades, there has been an overreliance in the prescription of opioids for chronic pain despite their poor ability to improve function and high addiction liability. This contributed to a significant and alarming epidemic of opioid overdose deaths and addictions. Innovative scientific solutions to develop alternative pain treatment options are thus critically needed. Through targeted research efforts, the NIH HEAL Initiative aims to support the development of safe and effective devices to treat pain with little or no addiction liability. This funding opportunity announcement (FOA) is designed to support interdisciplinary research teams of multiple PD/PIs to investigate the mechanism of action of device-based pain relief with the overall goal of optimizing therapeutic outcomes for FDA-approved or -cleared technologies. Program teams are expected to accomplish goals that require considerable synergy and collaborative interactions. Teams must leverage appropriate multi-disciplinary expertise to develop new principles and methods for experimentation, analysis, and interpretation. Teams are encouraged to consider objectives that will produce major advances in the field of device-based pain relief.

The purpose of the Knockout Mouse Phenotyping Project (KOMP2) is to produce a comprehensive resource of null-mutant mice, and associated phenotype data, for the purpose of elucidating functional information for each protein-coding gene in the mammalian genome. This Funding Opportunity Announcement (FOA) solicits applications for production and phenotyping centers that will make maximum progress toward completion of KOMP2 in a final five-year project period. The specific objectives are to generate approximately 1,200 mutant mouse lines using CRISPR/Cas9 technology, perform a series of phenotyping assays, cryopreserve germplasm, and make mice and data readily available to the research community. This is a limited competition RFA. Only recipient organizations funded under (RFA-RM-15-017) are eligible to apply.

The purpose of this request for administrative supplements to current NIH-fundedstudies is to encourage clinical and translational research that will increase our understanding of the prevalence, psychological variables, and response to therapy in those individuals with multiple chronic overlapping pain conditions (COPCs). Recent clinical findings suggest that substantial overlap may exist between chronic pain conditions. Individuals diagnosed with one pain disorder often exhibit characteristics of additional chronic painful conditions or transition to other diagnostic categories. A better understanding is needed of the characteristics of overlapping pain conditions, the progression of these conditions, and therapeutic approaches best suited for treating individuals with COPCs. Research efforts in chronic pain conditions have focused on single disorders or types of pain such as neuropathic and inflammatory pain. These research efforts have generated a substantial body of information advancing our understanding of the underlying mechanisms of pain onset and development, the transition from acute to chronic pain, and therapeutic targets for treating acute and chronic pain. Over the past twenty years reports have documented the presence of more than one chronic pain condition in subjects with pain. Studies have identified overlap between a number of chronic pain conditions, including lower back pain, fibromyalgia (FM), vulvodynia, endometriosis, functional gastrointestinal disorders such as irritable bowel syndrome (IBS), temporomandibular joint disorder (TMD), migraine, tension headache, low back pain, and urologic chronic pelvic pain syndromes (UCPPS). These results suggest that chronic pain conditions may not be localized conditions but may share symptoms and mechanisms that involve a general central nervous system dysfunction as well as disorder-specific symptoms.