Funding Opportunity PAR-25-036 from the NIH Guide for Grants and Contracts. This Notice of Funding Opportunity (NOFO) invites research grant applications that propose the development and evaluation of novel radioligands for positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging in human brain and the incorporation of, pilot or clinical feasibility evaluation from previously collected data in pre-clinical studies. These studies are expected to provide the requisite data needed to advance promising PET ligands for use in clinical research.

Funding Opportunity PAR-25-146 from the NIH Guide for Grants and Contracts. The purpose of this notices of funding opportunity (NOFO) is to support innovative research that will inform our understanding of the mechanisms underlying the formation of structural birth defects using animal models in conjunction with human translational/clinical approaches. Applicants are encouraged to take advantage of advances in genetics, omics methods (genomics, proteomics, metabolomics, etc.), and synthetic biology, biochemical and other approaches to developmental biology research to identify specific genetic, epigenetic, environmental, or gene/environment interactions associated with the formation of, susceptibility to, and variability of structural birth defects in human populations.

Funding Opportunity PAR-25-140 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications to phenotype and/or perform research on embryonic lethal knockout (KO) mouse strains being generated through the International Mouse Phenotyping Consortium (IMPC) of which the NIH Knockout Mouse Phenotyping Program (KOMP2) is a member. The mission of IMPC is to generate a comprehensive catalogue of mammalian gene function that will provide the foundation for functional analyses of human genetic variation. The current (July 19, 2022) IMPC data release includes phenotypic data for 8260 knockout genes. Overall, the IMPC hopes to generate a null mutant and undertake broad-based phenotyping for every gene in the mouse genome. About 30% of these strains are expected to be either embryonic or perinatal lethal, or subviable. However, a large portion of homozygous lethal mutations are expected to have viable heterozygous phenotypes. The scientific community has the unique opportunity to leverage these mouse strains while they are being created and bred as part of the IMPC adult mouse phenotyping effort to perform additional in-depth phenotyping and research.

Funding Opportunity PAR-25-227 from the NIH Guide for Grants and Contracts. The purpose of this Notice of Funding Opportunity (NOFO) encourages applications that will expand knowledge of the natural history of disorders that currently are, or may become, part of statewide newborn screening programs. A comprehensive understanding of the natural history of a condition is necessary to facilitate appropriate interventions for infants identified by newborn screening. Characterization of the sequence and timing of symptom development provides information crucial for developing targeted, age-appropriate treatments and for establishing a baseline against which to assess novel interventions. In addition, for some conditions, establishment of genotype-phenotype correlations may facilitate prediction of the clinical course; for others, identification of modifying genetic, epigenetic, or environmental factors may enhance understanding of clinical outcomes. Comprehensive data on the natural history of a condition will facilitate the fields ability to: 1) identify the underlying biological mechanisms; 2) understand the genetic and clinical heterogeneity and phenotypic expression of the condition; 3) improve diagnostic accuracy; 4) facilitate clinical trials by providing comprehensive natural history data; 5) prevent, manage, and treat symptoms and complications of the condition; 6) furnish physicians and families with needed support and predictive information about the condition; and 7) establish data collection systems or patient registries to collect longitudinal data (e.g., child/family outcomes following newborn screening).

Funding Opportunity PAR-25-117 from the NIH Guide for Grants and Contracts. The NIH Research With Activities Related to Diversity (ReWARD) Program's overarching goal is to enhance the breadth and geographical location of research and research-related activities supported by NIH. The ReWARD program provides support for the health-related research of scientists who are making a significant contribution to Diversity, Equity, Inclusion, and Accessibility (DEIA) and who have no current NIH research project grant funding. The ReWARD program provides funding for both the scientific research and the DEIA activities of investigators. The grant will support scientific research in areas related to the programmatic interests of one or more of the participating NIH Institutes and Centers (ICs) and DEIA activities focused on enhancing diversity in the biomedical research enterprise within the United States and territories.

Funding Opportunity PAR-25-153 from the NIH Guide for Grants and Contracts. Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) solicits applications for identification of small molecules that function to elucidate the biology of disease as chemical probes or function as agonists or antagonists of disease target(s) for therapy or immunotherapy. The NOFO is intended to support discovery research for the identification of validated hits relevant to health-related outcomes of participating NIH Institutes. Stages of discovery research covered by this NOFO include: 1) assay development for specific biological targets and disease mechanisms relevant to the mission of participating NIH Institutes with the intent to screen for small molecule compounds that show potential as probes for use in advancing knowledge about the known targets, identifying new targets, or as pre-therapeutic leads; 2) screen implementation high throughput target-focused approaches or moderate throughput phenotypic- and fragment-based approaches to identify initial screening hits; 3) hit validation, including implementation of secondary assays that are orthogonal to the primary assay, advanced cheminformatics analysis and initial medicinal chemistry inspection to prioritize the hit set, and follow-up assays to characterize mode and mechanism of action of the validated hits; 4) hit-to-lead optimization, including SAR to optimize target engagement, selectivity and to minimize chemical liabilities, ADME, PK and PD studies, and, if appropriate, in vivo modeling to test efficacy or biological effects.

Funding Opportunity PAR-25-145 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to support collaborative research projects designed to address adverse sequelae of cancer therapies that persist and become chronic comorbidities or develop as delayed posttreatment effects. This FOA supports basic, translational, and clinical research projects that seek to identify the mechanisms of therapy-induced adverse sequelae, clinically characterize the adverse sequelae, or translate the mechanistic understanding into therapeutic approaches to prevent or minimize the development of long-term sequelae. Research projects should focus on mechanistic studies with translational endpoints and longitudinal clinical phenotyping to identify and validate clinical endpoints (biomarkers, imaging, patient-reported outcomes, or combined elements) for future use in clinical trials that will evaluate the efficacy of interventions designed to prevent or reduce specific adverse sequelae.

Notice NOT-GM-25-007 from the NIH Guide for Grants and Contracts

Funding Opportunity RFA-NS-25-022 from the NIH Guide for Grants and Contracts. The purpose of this announcement is to encourage investigators to pursue a small clinical trial to obtain critical information necessary to advance recording and/or stimulating devices to treat central nervous system disorders and better understand the human brain (e.g., Early Feasibility Study). Clinical studies supported may consist of acute or short-term procedures that are deemed Non-Significant Risk (NSR) by an Institutional Review Board (IRB), or Significant Risk (SR) studies that require an Investigational Device Exemption (IDE) from the FDA, such as chronic implants. The clinical trial should provide data to answer key questions about the function or final design of a device. This final device design may require most, if not all, of the non-clinical testing on the path to more advanced clinical trials and market approval. The clinical trial is expected to provide information that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use. Activities supported by this Funding Opportunity include a small clinical trial to answer key questions about the function or final design of a device. As part of the BRAIN Initiative, NIH has initiated a Public-Private Partnership Program (BRAIN PPP) that includes agreements (Memoranda of Understanding, MOU) with a number of device manufacturers willing to make such devices available, including devices and capabilities not yet market approved but appropriate for clinical research. In general it is expected that the devices' existing safety and utility data will be sufficient to enable new IRB NSR or FDA IDE approval without need for significant additional non-clinical data. For more information on the BRAIN PPP, see http://braininitiative.nih.gov/BRAIN_PPP/index.htm

Funding Opportunity RFA-NS-25-021 from the NIH Guide for Grants and Contracts. The purpose of this announcement is to encourage investigators to pursue translational activities and small clinical studies to advance the development of therapeutic, and diagnostic devices for disorders that affect the nervous or neuromuscular systems. Activities supported in this program include implementation of clinical prototype devices, non-clinical safety and efficacy testing, design verification and validation activities, obtaining an Investigational Device Exemption (IDE) for a Significant Risk (SR) study, as well as a subsequent small clinical study. The clinical study is expected to provide information about the device function or final design that cannot be practically obtained through additional non-clinical assessments (e.g., bench top or animal studies) due to the novelty of the device or its intended use. This FOA is a milestone-driven cooperative agreement program and will involve participation of NIH program staff in negotiating the final project plan before award and monitoring of research progress.

Funding Opportunity PAR-25-104 from the NIH Guide for Grants and Contracts. The purpose of this FOA is to facilitate well planned clinical trials across the cancer prevention and control spectrum aimed at improving prevention/ interception, cancer-related health behaviors, screening, early detection, healthcare delivery, management of treatment-related symptoms, supportive care, and the long-term outcomes of cancer survivors. Although the scientific literature or preliminary data may provide the rationale for conducting a clinical trial, investigators often lack critical information about the study population, accrual challenges, intervention, outcome/ endpoints, data/statistical challenges or operational risks necessary to finalize the trial protocol completely. These information gaps can result in multiple protocol changes before and after trial start-up, leading to the need for additional time and expenses that may prevent study completion. Further, the suitability and feasibility of new trial designs, which minimize infrastructure and reduce costs may need to be tested in the context of a particular intervention, at-risk group, symptom or venue. Preparatory studies may fill information gaps and address unknowns, improving trial design and knowledge of trial feasibility and thus saving NCI time and money.

Funding Opportunity PAR-25-103 from the NIH Guide for Grants and Contracts. The purpose of this NOFO is to facilitate well planned clinical trials across the cancer prevention and control spectrum aimed at improving prevention/ interception, cancer-related health behaviors, screening, early detection, healthcare delivery, management of treatment-related symptoms, supportive care, and the long-term outcomes of cancer survivors. Although the scientific literature or preliminary data may provide the rationale for conducting a clinical trial, investigators often lack critical information about the study population, accrual challenges, intervention, outcome/ endpoints, data/statistical challenges or operational risks necessary to finalize the trial protocol completely. These information gaps can result in multiple protocol changes before and after trial start-up, leading to the need for additional time and expenses that may prevent study completion. Further, the suitability and feasibility of new trial designs, which minimize infrastructure and reduce costs may need to be tested in the context of a particular intervention, at-risk group, symptom or venue. Preparatory studies may fill information gaps and address unknowns, improving trial design and knowledge of trial feasibility and thus saving NCI time and money.

Funding Opportunity RFA-OD-25-002 from the NIH Guide for Grants and Contracts. This limited competition Notice of Funding Opportunity (NOFO) solicits continued participation as the Data Coordinating Center for the NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE).

Notice NOT-OD-25-019 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-25-225 from the NIH Guide for Grants and Contracts. Reissue PAR-21-122. This NOFO provides funding to conduct pharmacodynamic, pharmacokinetic, and in vivo efficacy studies to demonstrate that proposed therapeutic agent(s) have sufficient biological activity to warrant further development to treat neurological or neuromuscular disorders that fall under the NINDS mission. Therapeutic agents include small molecules, biologics or biotechnology-derived products. This FOA is part of a suite of Innovation Grants to Nurture Initial Translational Efforts (IGNITE) to advance projects to the point where they can meet the entry criteria for the Blueprint Neurotherapeutics Network or other translational programs.

Funding Opportunity RFA-AI-24-074 from the NIH Guide for Grants and Contracts. The purpose of this notice of funding opportunity (NOFO) is to support multidisciplinary research programs focused on discovery to early development research to inform new approaches to prevent, diagnose, and treat antibiotic-resistant bacterial infections.

Notice NOT-HS-25-008 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-25-139 from the NIH Guide for Grants and Contracts. Through this Notice of Funding Opportunity (NOFO), the National Cancer Institute (NCI) intends to supports the development of new exploratory research in cancer diagnosis, treatment, imaging, symptom/toxicity, and prevention clinical trials; correlative studies associated with clinical trials; novel cancer therapeutic, symptom/toxicity, and preventive agent development, radiotherapy development activities, and mechanism-driven combinations; and innovative preclinical studies--including the use of new clinically-relevant models and imaging technologies--which could lead to first-in-human clinical trials. The R21 mechanism is intended to encourage exploratory and developmental research projects by providing support for the early and conceptual stages of these projects. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of cancer research (pre-clinical or clinical).

Funding Opportunity RFA-DA-26-019 from the NIH Guide for Grants and Contracts. Emerging threats continuously evolve. Xylazine, nitazenes, and other future threats are making their way or are already in the drug supply. Understanding them requires analyzing real world samples. Typically, testing strips are used to detect drug for which such strip exists, as the strips are fast, sensitive, low cost and reasonably accurate. However, as there might not be testing strips for the new threats, the analysis must be performed via sensitive and sample agnostic methods.

Funding Opportunity RFA-DA-26-018 from the NIH Guide for Grants and Contracts. Emerging threats continuously evolve. Xylazine, nitazenes, and other future threats are making their way or are already in the drug supply. Understanding them requires analyzing real world samples. Typically, testing strips are used to detect drug for which such strip exists, as the strips are fast, sensitive, low cost and reasonably accurate. However, as there might not be testing strips for the new threats, the analysis must be performed via sensitive and sample agnostic methods.