NOT-NS-22-065: Notice of Intent to Publish a Funding Opportunity Announcement for HEAL Initiative: Discovery and Functional Evaluation of Human Pain-associated Genes & Cells (U19 Clinical Trial Not Allowed)

National Institute of Neurological Disorders and Stroke (NINDS)
National Institute on Aging (NIA)

The National Institutes of Health (NIH) intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications for a Data Coordination and Integration Center that will curate, harmonize, and integrate comprehensive -omics and cellular function datasets for the discovery and functional evaluation of human pain-associated genes and cells.

This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and develop responsive projects. The FOA is expected to be published in Winter, 2022 with an expected application due date in Spring of 2022.

This FOA will utilize a cooperative agreement mechanism (U24). Details of the planned FOA are provided below.

This funding announcement is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal.nih.gov/.

The NIH HEAL Initiative encourages research projects that aim to use human cells and tissues to accelerate the discovery and successful translation of pain therapeutics by supporting collaborative efforts to gain a better, more direct understanding of human pain-associated genes and functional elements that underly specific human pain types, conditions and/or diseases. Towards this end, the NIH HEAL Initiative has developed a Program to Reveal and Evaluate Cells-to-gene Information that Specify Intricacies, Origins and the Nature of Human Pain (PRECISION Human Pain). PRECISION Human Pain will be comprised of a group of centers supported via two planned FOAs; one to support U19 Centers for the Discovery and Functional Evaluation of Human Pain-associated Genes & Cells (described in NOT-NS-22-065), and another to support a U24 Human Pain-associated Genes & Cells Data Coordination and Integration Center. It is expected that PRECISION Human Pain Centers will work together, operating as a cooperative network to achieve its key objectives.

The goal of the PRECISION Human Pain network is to use human cells and tissues to build up comprehensive datasets of molecular signatures, cell types, and cellular function phenotypes or signatures that underlie human pain signal transduction, transmission, and processing. Areas of interest for the network are not limited to specific pain types, conditions and/or diseases. Projects that propose to use human cells and tissues from multiple pain conditions in the context of chronic analgesic use, other drug use, substance use disorders (SUDs) and other co-morbid and/or overlapping pain conditions are encouraged.

Key objectives of the PRECISION Human Pain network will be to:

• Elucidate and validate functional roles of human genes and cellular phenotypes underpinning the heterogeneity, pathogenesis and susceptibility to specific pain conditions.
• Enable and accelerate the discovery and validation of condition/disease-specific human pain therapeutic targets with enhanced translational potential.

Research Objectives

The planned U24 Data Coordination and Integration Center will play two critical roles for the PRECISION Human Pain network. One will be to work closely with the network’s U19 Centers to adopt and promote standard terminology, data acquisition protocols, quality control metrics, and metadata requirements to enhance data interoperability and harmonization across the network and the broader research community. The second will be to extract, accumulate, organize, annotate, and link growing bodies of information related to core datasets generated by the U19 Centers. These datasets are expected to include elements such as molecular signatures (e.g., transcriptome, epigenome, proteome, metabolome), anatomy (e.g., cell and nerve/neurite location, size, orientation, morphology, and connectivity), and function (e.g., electrophysiology, functional connectivity), all derived from primary human tissues involved in pain processing, including but not limited to dorsal root ganglia (DRG), spinal cord (SC), trigeminal ganglia (TG), sympathetic ganglia (SG), brainstem, brain, peripheral nerve bundles/fibers, and skin.

Working with the NIH HEAL Initiative’s Public Access and Data Ecosystem (https://heal.nih.gov/about/public-access-data) and aligning with its guidelines and infrastructure, the U24 Data Coordination and Integration Center will establish a web-accessible information system to capture, temporarily store, analyze, and curate all high-throughput multi-omics data and metadata for different pain-associated human cell types and tissues. The Center will also integrate datasets and generate resources, such as interactive 2D and 3D maps, machine-readable protocols, data dictionaries, and other materials, that can be used widely by the research community.

The comprehensive -omics and cellular function datasets generated from PRECISION Human Pain network will significantly accelerate first-hand validation of pain therapeutic targets in human pain-relevant cells and tissue. These studies will also facilitate the identification and development of potential markers that reflect target engagement, thus providing valuable assets for translational research and therapeutic development. In all, the integrated datasets and digital resources developed through this initiative will be highly informative for multiple ongoing and future pre-clinical and translational programs in the NIH HEAL initiative and the NIH more broadly.

Applicants are strongly encouraged to consult with NIH program staff as plans for an application are being developed.