NOFO: Targeting Inflammasomes in Substance Abuse and HIV (US)

Deadline: 16-Feb-23

The National Institutes of Health (NIH) invites applications to investigate the underlying mechanisms and CNS consequences of the interactions of addictive drugs and HIV-1 infection on inflammasome assembly and activation.

The goal of this Funding Opportunity Announcement (FOA) is to encourage research to explore mechanisms of inflammasome activation, humoral immune reaction and potential antibody-mediated enhancement, and their link to immune functions in people with HIV and substance use disorders (SUDs).

This FOA supports studies to either (1) elucidate the mechanisms of inflammasomes in virus and drug-induced immune activation, or (2) identify molecular markers and CNS immune cells associated with HIV-1 infection or disease progression among individuals with SUD. Success of these projects may lead to development of novel therapies that target inflammasome activation or suppression to treat neuroinflammation and immune dysregulation in people with HIV.

Research Areas

• The FOA invites applications to investigate the underlying mechanisms and CNS consequences of myeloid cell-triggered inflammasome activation in the context of comorbid HIV-1 infection and acute or chronic substance use. Research areas that are pertinent to this FOA include, but are not limited to:
  • Identify and characterize common and specific inflammasome pathways within the CNS activated by addictive drugs and HIV-1 infection
  • Differential expression of inflammasomes and the structural and functional consequences of inflammasome activation in different anatomical brain regions under the influence of SUD and HIV-1 infection
  • Differential expression and activation of inflammasomes in CNS cells – including resident myeloid cells (such as microglia and perivascular macrophages), astrocytes, oligodendrocytes and neurons – in the presence of addictive drugs and HIV-1 infection
  • Impact of addictive substances and HIV on myeloid cell mediated inflammation in CNS
  • Heterogenous inflammasome signatures in CNS myeloid cells and their use as biomarkers of neuroinflammation in people use addictive substances and live with HIV
  • Role of inflammasomes in humoral and cellular immune responses against HIV in people with substance use history
  • Mechanistic studies of myeloid cell-mediated inflammasome activation and its impact on cognition and behavior
  • Studies characterizing mechanisms of myeloid cell-mediated inflammation and their influence on HIV infection, spread and persistence in CNS
  • Studies exploring immunotherapies targeting myeloid cells and their functions in the context of substance use and HIV infection
  • Determine the effect of combination antiretroviral therapy (cART) on inflammasome dynamics and activation
  • Identify and develop pharmacological approaches that regulate initial inflammasome activation in the context of SUD and HIV-1 infection
  • Interactions between innate immune/inflammasome activation and B cell perturbations in HIV under ART
  • Impact of B cell perturbations and/or autoimmunity on HIV pathogenesis, and mechanisms involved

Funding Information

• NIDA intends to support up to 6 awards for RFA-DA-24-003 and RFA-DA-24-004, corresponding to a total of $ 4,000,000 in FY 2024. Future year amounts will depend on annual appropriations.
• Application budgets are limited to $500,000 direct costs per year and  need to reflect the actual needs of the proposed project.
• Duration: The maximum project period is five years.

Eligibility Criteria

• Higher Education Institutions
  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education
• The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
• Nonprofits Other Than Institutions of Higher Education
  • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
  • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• For-Profit Organizations
  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)
• Local Governments
  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)
• Federal Government
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession
• Other
  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
• Foreign Institutions
  • Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
  • Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
  • Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

For more information, visit https://www.grants.gov/web/grants/view-opportunity.html?oppId=344372