Create Research Tools for Difficult-to-Culture Eukaryotic Pathogens

Funding News Edition: September 20, 2023
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A lack of sufficient genetic tools and culture conditions has blocked the development of medical countermeasures for select human eukaryotic pathogens including the microsporidian Enterocytozoon bieneusi; Pneumocystis jirovecii, Plasmodium vivax; and Babesia microti.

A targeted initiative that decouples tool generation from fundamental hypothesis-driven research will address these deficiencies by exploring the availability of genetic tools and experimental culturing conditions for these pathogens.

Through the notice of funding opportunity (NOFO): Research Tools for Difficult to Culture Eukaryotic Pathogens (R61/R33, Clinical Trial Not Allowed), NIAID invites applications on high-risk, milestone-driven research for tool discovery to develop genetic manipulation or long-term in vitro or ex vivo culture conditions for these select pathogens. The exquisite host tropism of these pathogens may necessitate that nonhuman pathogenic species serve as models while developing these basic research tools. We encourage research teams to enlist cross-collaborative, multi-disciplinary efforts from other fields to overcome longstanding scientific hurdles; extensive preliminary data are not required. Research strategies should represent a significant advancement and yield easily adaptable transformational tools.

Specific Areas of Research Interest

Below are examples of research that are within the scope of the NOFO:

  • Development or optimization of primary cell culture, stem cell technology, air-liquid interface systems, organoid models, or unique in vivo model systems to support stable pathogen replication that represent a major advance over current standards.
  • Development of tools for genetic manipulation to enable insertion, deletion, or overexpression of genes within these select pathogens.

We will consider applications in the following areas to be nonresponsive and will not review them:

  • Research focusing on pathogens other than: microsporidian Enterocytozoon bieneusi; Pneumocystis jirovecii; Plasmodium vivax; or Babesia microti.
  • Research proposing an R33 phase that does not utilize tools generated within the R61 phase.
  • Applications that do not provide a milestone section in the R61 phase.
  • Applications with clinical trials.

Phased Innovation Awards

Due to the high-risk, high-impact nature of this research, we will use the R61/R33 Exploratory/Developmental Phased Award activity code. In the R61 phase, you can apply for up to 3 years of support for milestone-driven research to develop robust culture techniques and detailed protocols, or genetic and molecular tools to better understand the biology of these select eukaryotic pathogens. This phase should be dedicated to the production of research tools only, and not to testing hypotheses on pathogen biology.

Before the end of the R61 phase, you will submit an R33 transition package, which will include a detailed progress report describing advancement toward the initial milestones and a description of how the completed work justifies continuation with the originally proposed R33 research. NIH program staff will review your materials and decide whether your award may transition to an R33 award. A transition to the R33 phase is neither automatic nor guaranteed and a funding decision is based on the original R61/R33 peer review recommendations, successful completion of R61 milestones, program priorities, and availability of funds.

Award Budget Information

The budget cap for the R61 phase is $250,000 in annual direct costs, and the budget for the R33 phase is $350,000 in annual direct costs. The maximum project period for the R61 phase is 3 years and the maximum project for the R33 phase is 2 years, for a total of 5 years for the entire R61/R33 award.

Applications are due on February 2, 2024, by 5 p.m. local time of the applicant organization.

NIAID intends to fund six to eight awards in fiscal year 2025. 

Pathogen-Specific Contact Information

Send Plasmodium vivax or Babesia microti related research questions to Dr. Glen McGugan, at or 240-627-3314. Send microsporidian Enterocytozoon bieneusi and Pneumocystis jirovecii related questions to Dr. Dona Love, at or 301-761-7788.

For questions related to peer review, contact Dr. Richard Kostriken at or 240-731-2021.

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