Applying Imaging Pipelines for Spatial Characterization of Cellular Interactions in HIV-related CNS Pathology and/or Substance Use (R61/R33 Clinical Trial Not Allowed) | RFA DA 24 030

Opportunity Information: Apply for RFA DA 24 030

This funding opportunity (RFA-DA-24-030) from the National Institutes of Health supports projects that build and use advanced ex vivo imaging approaches to better understand how cells interact with each other in the central nervous system (CNS) in the context of HIV infection, HIV persistence, and related brain pathology, including pathology that may be linked to substance use. The core idea is to move beyond studying CNS HIV in bulk tissue averages and instead produce spatially resolved, highly detailed maps that show where specific cell types are located, how they are organized, and how they communicate or interact within intact or semi-intact tissue. The emphasis is on pairing innovative imaging with the full set of enabling steps needed to make the science work end to end, including tissue acquisition, tissue handling and processing, and the computational pipelines required to analyze and annotate the spatial data with molecular information.

The NOFO is structured as an R61/R33 phased innovation award mechanism and is explicitly labeled “Clinical Trial Not Allowed,” which signals that the supported work is not intended to be an interventional clinical trial. In practical terms, this mechanism is commonly used for projects that need an initial, milestone-driven development phase (R61) to establish feasibility, optimize methods, and prove that the approach can generate usable data, followed by an expansion or implementation phase (R33) where the validated pipeline is applied more broadly to answer biological questions. For applicants, this means the proposal typically needs to describe both phases: what will be built and de-risked early on, what objective benchmarks will be used to decide readiness to transition, and what biological or neuropathological questions will be addressed once the pipeline is working reliably.

Scientifically, the opportunity prioritizes spatial characterization and molecular annotation of intercellular interactions in CNS HIV. That includes understanding how infected or reservoir-associated cells may be distributed in the brain, how immune cells and glial cells respond in specific microenvironments, and how these patterns relate to neuropathology. Because the NOFO also references substance use, it is positioned to support studies that examine how substance exposure or use-related conditions might change cellular neighborhoods, inflammatory signaling, neuroimmune interactions, or tissue architecture in ways that influence HIV persistence or CNS damage. The imaging component can reasonably encompass modern spatial technologies such as multiplexed immunofluorescence, high-parameter microscopy, spatial transcriptomics used in an imaging-guided manner, or other advanced approaches, as long as the project delivers spatially explicit data and integrates that data with molecular labels or annotations that clarify which cells are interacting and what functional states they exhibit.

A key feature of the announcement is that it does not just fund a single imaging assay in isolation. It calls for complete pipelines, meaning applicants are expected to think through and propose a coherent workflow from tissue procurement to final spatial analytics. Tissue procurement and processing are called out as necessary elements, which usually implies attention to factors like post-mortem interval considerations, fixation and sectioning strategies, preservation of antigenicity or RNA quality, batch effects, and standardized metadata collection so that results can be interpreted across samples. On the computational side, the NOFO highlights the need for computation pipelines capable of handling large imaging datasets, performing tasks such as cell segmentation, cell type classification, spatial statistics, neighborhood analysis, and integration with molecular features, ultimately enabling interpretable maps of cell-cell relationships relevant to HIV neuropathogenesis.

Eligibility is broad and includes many organization types that commonly participate in NIH funding, such as state, county, city, and special district governments; public and private institutions of higher education; independent school districts; public housing authorities/Indian housing authorities; federally recognized Native American tribal governments; and Native American tribal organizations that are not federally recognized. It also includes nonprofit organizations (both with and without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and other entities. The announcement explicitly notes additional eligible applicant categories that NIH often highlights to encourage diverse participation, including Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, U.S. territories or possessions, and non-U.S. (foreign) organizations. Taken together, this indicates NIH is open to applications from a wide range of research environments, including international groups, as long as they can execute the required tissue, imaging, and analytics work.

From an administrative snapshot, this is a discretionary grant opportunity in the NIH education/health activity area, associated with CFDA number 93.279. The original closing date listed is 2024-02-08. The opportunity lists an award ceiling of $300,000, indicating a cap on the amount that can be requested under the terms shown in the source data (applicants would still need to follow the NOFO-specific budget guidance and any phase-specific constraints typical of R61/R33 awards). The listing also shows the expected awards field without a number, so the total number of awards is not clearly specified in the provided excerpt.

Overall, the opportunity is aimed at teams that can bring together neuropathology, HIV neuroscience, imaging technology, tissue handling expertise, and computational biology to produce actionable spatial maps of CNS cellular interactions. Competitive projects are likely to be those that demonstrate technical innovation in imaging, strong control of tissue-related variables, and a realistic, well-validated computational strategy for converting complex images into quantified, biologically meaningful descriptions of how cells interact in HIV-related CNS disease and, where relevant, substance use contexts.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Applying Imaging Pipelines for Spatial Characterization of Cellular Interactions in HIV-related CNS Pathology and/or Substance Use (R61/R33 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.279.
• This funding opportunity was created on 2023-10-16.
• Applicants must submit their applications by 2024-02-08. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $300,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA DA 24 030

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