To meet an urgent and unmet need, NIAID established the Chemical Countermeasures Research Program (CCRP) as a trans-NIH initiative in 2006. Its purpose is to support the discovery and early development of medical countermeasures (MCMs) that can treat or prevent morbidities and death during or after mass casualty public health emergencies involving highly toxic chemicals.
You can apply for funding through two new notices of funding opportunities (NOFOs) to conduct basic research on fundamental mechanisms of chemical toxicity and identify potential molecular/genetic targets that may be interrogated to reduce acute or long-term chronic adverse health effects after exposure:
Research Objectives
These two NOFOs intend to support fundamental research that characterizes the acute or long-term pathophysiological effects on the pulmonary, ocular, or neurological system, via interrogating cellular, biochemical, and molecular mediators and pathways, after chemicals of concern (CoC) exposure. Additionally, the NOFOs encourage researchers to pursue studies using diverse animal models, organoid tissues, ex vivo studies using human or animal tissues, in vitro cell culture systems, or in silico models.
We encourage projects interested in understanding the impact on diverse comorbidity factors such as age, sex, pregnancy, or pre-existing disease conditions.
Pulmonary Toxicant Research Topics of Interest
CoCs of pulmonary interest include those that induce pulmonary edema, pneumonitis, and fibrosis (e.g., chlorine, phosgene, sulfur mustard, nitrogen mustard, and oleum).
Potential applicants should consider the following:
- Studies proposing to use in vitro models should include at least one cell culture model with at least two different cell types relevant to the target organ, and two or more toxicants and multiple time points post exposure. We will deem applications using only immortalized or transformed cell lines or only one toxicant to be nonresponsive.
- Applications using animal models should use at least two different species or strains and both sexes, or collaborative cross strains or knock out models and both sexes, and a minimum of two toxicants as well as multiple time points post exposure to gain comparative understanding of the toxic effects. We will deem applicants using only one sex or one species or strain or one toxicant to be nonresponsive.
- Studies investigating the role of susceptibility in the manifestation of toxic effects should use neonate, adult, old or aged animals of both sexes, and assays performed at multiple time points post exposure and a minimum of two toxicants. We will deem applications using only one sex, one susceptibility condition, or one toxicant to be nonresponsive.
- Studies proposing use of high throughput screening approaches, such as organoid tissue systems should use more than two toxicants and multiple time points post exposure that will facilitate cross comparison analysis for identifying common molecular targets.
- Applications that use a combination of in vitro, ex vivo, or in vivo studies should use a minimum of two toxicants and both sexes with data generated at multiple time points post exposure. We will deem applications with one sex, toxicant, or time point to be nonresponsive.
- NIAID encourages applications using in silico and computational predictive modeling approaches for acute lung injury mechanisms.
- We encourage applications involving delayed response studies of acute toxicant exposure to include acute response studies in two species/strains and both sexes, and to provide a strong justification for selection of one strain or one sex for investigations focused on delayed responses. The delayed response studies should include a time point of at least 45 days.
For pulmonary toxicant research topics, apply through RFA-ES-24-005.
Ocular Toxicant Research Topics of Interest
The eyes are usually the first and most frequent route of toxic exposure, making them especially vulnerable to chemically induced injuries. Compared to both the lungs and skin, ocular chemical injury typically manifests earlier and at lower toxicant concentrations. Dissecting and counteracting the eye’s vulnerability to chemical injury requires traction in at least four domains: responses to corneal toxicity (acute and chronic); models of corneal toxic injury; mechanisms of corneal pathologies and wound healing; and therapies for corneal pathology.
Potential applicants should consider the following:
- Chemical injury to the eye can result in a cascade of pathology: pain, photophobia, corneal epithelial defects, keratitis, endothelial cell loss, edema, inflammatory response, conjunctivitis, tear disruption, neovascularization, corneal scarring, opacity, and blindness. We are particularly interested in projects that explore multiple angles of this pathology.
- The first three-layer plan of the mammalian cornea raises the need to examine chemical toxicity across the epithelial, stromal, or endothelial layers (e.g., continuum of the injury and recovery process).
- The tear film is important to the function of the ocular surface and highlights the importance of an integrative investigation of ocular responses to chemical injury.
- Early/acute effects tend to resolve following chemical injury but then rebound as late/chronic effects. Shedding light on this delayed response is a particularly valuable objective of this NOFO.
- Proposed therapies against ocular chemical injury include anti-inflammatory, anti-fibrotic, anti-neovascular, and antioxidant agents but frequently result in incomplete or transient efficacy. Therefore, discovery of biologically active tools or probes to address the natural history of chemical ocular injuries is an important area of research interest covered under this NOFO.
- Replication of findings in more than one animal model raises confidence in the rigor of the obtained results.
- Inclusion of in vitro or in silico technologies to minimize the number of animal subjects.
For ocular toxicant research topics, apply through RFA-ES-24-005.
Whether your interest is in pulmonary or ocular toxicant research topics, note that we will consider applications to RFA-ES-24-005 to be nonresponsive if they propose the following:
- Applications that propose to study chemicals that are not on the DHS CoC list.
- Projects addressing health outcomes due to prolonged or persistent environmental or occupational chemical exposure.
- Efficacy studies, e.g., creation and validation of candidate MCMs.
Note also that all applications must include a letter from appropriate institutional biosafety officials indicating that studies are deemed safe for research personnel and the environment.
Neurological Toxicant Research Topics of Interest
You may propose basic research to inform toxicology of chemical warfare agents and select toxic industrial chemicals and materials that have primary or secondary effects on the nervous system. The proposed research must address immediate or long-term neurological effects following a single acute toxic exposure event. The scientific scope is elucidation of mechanism(s) of toxicity and pathology.
The categories of research supported under this initiative include, but are not limited to:
- Basic research to identify and validate molecular mechanisms of acute toxicity to chemical agents with primary or secondary effects on the nervous system that support identification of relevant biological markers and/or targets for therapeutic development.
- Elucidating the mechanistic basis of long-term effects of one-time acute CoC exposure.
- Development of in silico, in vitro, and in vivo models to elucidate known and unknown mechanistic pathways of toxicity.
- Using in vivo models for natural history studies of toxicity of CoCs.
- Basic research to identify and validate the mechanistic linkage between signaling molecules and their biological targets and deciphering their functional relationships and physiological roles to better understand toxicity of acute exposures from chemical threats with primary or secondary effects on the nervous system.
- Mechanisms of toxicity that are not addressed by the current standard of care for CoC (if applicable, e.g., nerve agents, cyanide), including mechanisms or targets that mitigate refectory status epilepticus (SE) and post SE neuropathology after acute exposure to chemical threats.
- Mechanisms of toxicity that cause neurodegeneration or alter neurodevelopment, the brain environment, the blood-brain barrier, neurogenetics, neural excitability, or neural circuitry.
For neurological toxicant research topics, apply through PAR-24-030.
We will consider applications nonresponsive and not review them if they include:
- Efficacy studies, e.g., creation and validation of candidate MCMs.
- Clinical trials.
- Applications that propose to study chemicals that are not on the DHS CoC list or applications that propose to study CoC that have primary effects on the pulmonary system, skin, and eyes, or on opioid chemical threats.
- Projects that do not address health outcomes after a single acute exposure, i.e., prolonged or persistent chemical exposure.
All applications must include a letter from appropriate institutional biosafety officials indicating that studies are deemed safe for research personnel and the environment.
Application Requirements
For both NOFOs, application budgets are limited to $300,000 in annual direct costs and need to reflect the actual needs of the proposed project. Additionally, for pulmonary or ocular toxicant research topics, the budget allocation for in vitro or in silico research cannot exceed $200,000 in direct costs per year.
The scope of the proposed project should determine the project period, which cannot exceed 3 years.
Both NOFOs limit eligibility to domestic (U.S.) organizations, though Foreign Components are allowed.
The submission deadlines for RFA-ES-24-005 are September 24, 2024; September 24, 2025; and September 23, 2026. The submission deadlines for PAR-24-030 are October 17, 2024; October 17, 2025; and October 16, 2026.
Contact Information
Direct any questions to NIAID’s scientific/research contact Dr. Dave Yeung at dy70v@nih.gov or 301-761-7237.