Grants for State Governments

FOA Modification 000001: The purposes of this modfication are to: 1. Extend the Letter of Intent submission deadline on FOA page 1; 2. Revise the Letter of Intent submission process in FOA Section V.C; and 3. Increase the resume page limit in FOA Section V.D.iii. ---------------------------------------------------------------------------------------------------------------- Inflation Reduction Act (IRA) of 2022: State-Based Home Energy Efficiency Contractor Training Competitive Grant Program: The State-Based Home Energy Efficiency Contractor Training Grants, also known as the Training for Residential Energy Contractors (TREC) Program, seeks to accomplish three goals: (1) reduce the cost of training contractor employees by providing workforce development tools for contractors, their employees, and individuals including, but not limited to, subsidizing available training, testing certifications, and licenses for high-quality jobs; (2) provide testing and certifications of contractors trained and educated to install home energy efficiency and electrification technologies and deliver residential energy efficiency and electrification improvements; and (3) fund states to partner with nonprofit organizations to develop and implement a State sponsored workforce program that attracts and trains a diverse set of local workers to deliver the influx of new federally-funded energy efficiency and electrification programsincluding the IRA-funded Home Efficiency Rebates Program, Home Electrification and Appliance Rebates Program (Home Energy Rebates Programs); and Energy Efficiency Home Improvement Credit. This program was established by Section 50123 of the Inflation Reduction Act. For this competitive program, DOE is making up to $40 million in TREC funds available to states, territories, and the District of Columbia to complement the previously announced TREC formula funding. Topic Area Description Topic Area 1: Training Small Contractor Firms State Energy Offices may use topic area one funding to train and certify small contractor firms and their employees to deliver energy efficiency and electrification improvements. DOE will fund States to support existing small contractor firms through training and certifications so that the contractor firm employees can deliver energy efficiency and electrification improvements eligible for rebates under the Home Efficiency Rebates Program or the Home Electrification and Appliance Rebates Program. Topic Area 2: Innovative, Effective, and Equitable Workforce Development Programs State Energy Offices may use topic area two funding to implement innovative, effective, and equitable workforce development program models that deliver contractor training program curriculum. States can collaborate with nonprofit organizations to design/enhance and implement workforce development, training, certification, and employment programs that train, test, and certify underrepresented populations, new entrants to the workforce, youth ages 17-25, incumbent workers, displaced workers, and contractors to conduct home energy efficiency and electrification improvements under the Home Energy Rebates Programs. To view the full FOA Document and to register to apply for the FOA, go to Infrastructure eXCHANGE at https://infrastructure-exchange.energy.gov, the online application portal for the DOE Office of State and Community Energy Programs (SCEP).

The Rural program is dedicated to enhancing surface transportation infrastructure within rural communities, with $780 million allocated for this purpose. It supports highway, bridge, and tunnel projects that improve freight, safety, and access to agricultural, commercial, energy, or transportation facilities critical to a rural area's economy. This program recognizes the unique challenges faced by smaller communities in accessing funding and aims to support projects that address these needs directly. The submission deadline is May 6, 2024.

The Silicon Carbide (SiC) Packaging Prize, a three-phase competition launched by the U.S. Department of Energy’s (DOE’s) Office of Electricity, aims to accelerate the development of state-of-the-art SiC packaging prototypes. This initiative aligns with the DOE's mission to advance energy technologies and strengthen grid-based applications. The program's core objective is to push the industry beyond its current limitations in semiconductor packaging, specifically targeting the expansion of SiC power module capabilities to handle higher voltage and current. By fostering innovation in SiC packaging, the DOE seeks to enable more efficient and robust high-performance power electronics for future grid applications. The target beneficiaries of this prize are private entities (for-profits and nonprofits), nonfederal government entities (states, counties, tribes, and municipalities), academic institutions, and individuals based in the United States. The impact goal is to develop 10-kV, 2,000-A rated SiC power modules, addressing existing challenges such as parasitic inductance and heat dissipation that limit the performance of current SiC power modules. The program prioritizes solutions related to the SiC semiconductor packaging industry, with the majority of activities performed in the U.S. and benefiting the U.S. market. It seeks innovations that move the industry forward, are based on fundamental technical principles, and demonstrate a clear intent for commercialization and the establishment of viable U.S.-based businesses. The competition is structured into three phases, each with specific focuses and expected outcomes. Phase 1, "Design Study," requires competitors to describe their teams, plans, and current prototypes, with the goal of developing design documents for a Phase 2 prototype. Phase 2, "Initial Demonstration," will see winners from Phase 1 showcasing advancements in packaging solutions, aiming for progress towards Phase 2 performance metrics and innovation beyond the state-of-the-art. Finally, Phase 3, "Final Demonstration," focuses on achieving high voltage and high current targets for SiC modules, demonstrating significant improvements in packaging solutions and creating transformative technologies. Measurable results are tied to the prize structure, with financial incentives at each phase. Phase 1 offers up to 10 winners $50,000 each, Phase 2 provides up to 4 winners $250,000 each, and Phase 3 culminates with up to 1 winner receiving $750,000. These prizes incentivize progress towards the ultimate goal of developing advanced SiC power modules, with the program's strategic priority being the commercialization of early-stage technology and the growth of U.S.-based businesses. The theory of change behind this prize is that by fostering competition and providing financial support, the DOE can stimulate rapid innovation in a critical technology area, thereby improving grid reliability and performance while bolstering domestic manufacturing capabilities.

This(NOFO) aims to innovate, implement, and evaluate approaches to One Health laboratory diagnostic network optimization and specimen transport in Liberia. This multi-component NOFO is designed to address the inter-dependence of a comprehensive, resource-mapped, accredited national and sub-national laboratory network, the physical transportation architecture required to transfer network commodities (namely human, animal, and environmental specimens) point-to-point, and the optimization of digital communication, information, and supply chain systems necessary to sustain the network itself.

The purpose of this notice of funding opportunity (NOFO) is to solicit applications to participate in the Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP), a multi-center program dedicated to resolving immunologic and physiologic barriers to safe and efficacious xenotransplantation using preclinical pig to nonhuman primate (NHP) or human decedent models of pancreatic islet, kidney, heart, lung, or liver xenotransplantation. Transplantation is often the preferred or only therapy for end-stage organ disease. In 2023, 46,630 organ transplants were performed in the United States. In addition, transplantation of pancreatic islets offers a potential therapy for individuals with type 1 diabetes whose disease is not effectively managed with exogenous insulin. Unfortunately, with over 103,500 adults and children on the United Network for Organ Sharing (UNOS) waiting list, those in need of a transplant greatly exceed the number of available organs. It is estimated that 20 people on average die each day waiting for a transplant. Xenotransplantation offers a potential interim or definitive solution to the severe shortage of human organs and pancreatic islets. Pigs are the primary species of interest as xenograft donors due to their favorable reproductive capacity, and anatomical and physiological similarities to humans. However, there are multiple barriers to successful clinical xenotransplantation, including immunologic rejection of non-human organs and tissues by the human immune system, physiological differences between non-human and human molecules that prevent proper functioning of various biochemical pathways, and potential transmission of zoonoses. To address these challenges, the IXCRP was established by the National Institute of Allergy and Infectious Diseases (NIAID) in 2005 with a co-fund for type 1 diabetes from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (RFA-AI-04-042). Subsequently, in 2010, the program was renewed solely by NIAID (RFA-AI-09-035), in 2015 (RFA-AI-14-047 and RFA-AI-14-048), and in 2020 (RFA-AI-19-042 and RFA-AI-19-043). IXCRP investigators and other researchers in the field have made significant advances over the past two decades, and NIAID is committed to support this challenging area of research. Historically, the most significant hurdle to successful xenotransplantation was hyperacute rejection caused by preformed, xenoreactive naturally-occurring antibodies (XNA) that destroy the xenograft within hours post-transplant. The primary target of XNA is a carbohydrate epitope, galactose-alpha-(1,3)-galactose (Gal), which is not present in humans and Old World NHPs. To overcome this hurdle, two decades ago, the enzyme responsible for terminally linking Gal onto oligosaccharide chains, alpha-1,3 glycosyltransferase (GT), was knocked out in genetically modified pigs. Xenografts from GT knockout (GTKO) pigs elicit substantially less severe hyperacute rejection in NHPs. Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene knockouts and mutations to beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) were similarly engineered to reduce reactivity to other notable XNA to pig carbohydrate antigens, namely N-glycolylneuraminic acid-modified glycans and SDa swine blood group antigen, respectively. Over the last decade, application of CRISPR-Cas 9 technology combined with somatic cell nuclear transfer cloning has significantly accelerated the pace of multi-gene modification and donor pig production. Additional genetic modifications, most on the GTKO background, were developed to address key species-to-species incompatibilities and create more human-like organs. These include the insertion of human complement regulatory proteins to minimize the deleterious effects of the complement cascade in antibody-mediated rejection, human thrombomodulin and/or tissue factor pathway inhibitor to overcome coagulation pathway dysfunction, and human anti-inflammatory and/or immune suppressive genes to reduce immune activation contributing to graft rejection. These strategies have dramatically reduced the frequency and severity of hyperacute rejection and have prolonged survival in pig-to-NHP xenotransplantation models for up to 4 years. Success in prolonging xenograft survival in the pig-to-NHP model allows more in-depth investigation of the remaining immunologic and physiologic issues that must be addressed in order to achieve safe and efficacious clinical xenotransplantation. These include physiologic differences that influence xenograft function and long-term survival, and risks associated with zoonoses. Transmission of pathogenic zoonoses to a human recipient and, potentially, the general population is a concern. To reduce this risk, animals used for xenotransplantation are bred in specific-pathogen-free conditions, weaned early or caesarian-derived, and routinely screened to eliminate most, if not all, known zoonotic agents. Porcine Cytomegalovirus (PCMV) is a swine pathogen known to have deleterious effects on xenograft survival. In the first human patient to receive a cardiac xenotransplant, conventional testing failed to detect latent PCMV in the donor pig and the virus reactivated post-transplant. The extent to which PCMV reactivation contributed to the patient’s death is unknown; however, this event underscores the need for sensitive and reliable assays to detect both latent and active infection with PCMV. Porcine endogenous retroviruses (PERV), another potential zoonotic threat, were successfully inactivated in a line of pigs through a combination of CRISPR-Cas9 gene-editing and somatic cell nuclear transfer, further highlighting the potential of these technologies to both protect against immunologic attack and reduce the risk of zoonoses. The field of xenotransplantation has recently witnessed an expansion in research models beyond NHP recipients to include an evaluation of safety, feasibility, and short-term outcomes (2 – 60 days) in humans declared to have irreversible loss of brain function (individuals with brain death, also referred to as human decedents) maintained on cardiopulmonary support. These experiments, using varying genetically modified pig hearts and kidneys transplanted into human decedents whose organs were declined for allotransplantation based on organ quality, have demonstrated early hemodynamic stability, an absence of hyperacute rejection, and basic organ functionality under immunosuppression. No chimerism or transmission of porcine retroviruses were detected; however, many of these experiments have demonstrated thrombotic microangiopathy and/or antibody-mediated injury. As of the time of this writing, medical teams that include IXCRP-funded investigators have performed two pig-to-human orthotopic heart transplants under expanded access (compassionate use) authorization from the FDA. The two xenograft recipients expired at 8 and 6 weeks, respectively. These initial clinical xenotransplants demonstrated good early xenograft function but also highlighted fundamental gaps in our knowledge of 1) critical pathways leading to inflammation and graft failure, 2) best practices for zoonotic viral surveillance and treatment, 3) optimal design of the donor pig, and 4) postoperative immunosuppression regimen. These knowledge gaps must be addressed prior to broader clinical translation. Scope and Research Objectives The re-issue of the IXCRP will support research projects centered around preclinical NHP and/or human decedent models of porcine pancreatic islet, kidney, heart, lung, or liver xenotransplantation. The research objectives must address one or more of the remaining key immunologic and physiologic barriers to achieving safe and efficacious xenotransplantation, including issues affecting engraftment, survival, and function of xenografts. Research foci may include 1) development or optimization of the models themselves, including genetic modifications of the pig-donor to address FDA concerns, as well as refinement of surgical xenotransplantation techniques, 2) development or optimization of the immunosuppression (IS) regimen to prevent rejection and minimize toxicity, 3) characterization and resolution of physiological and immunological barriers to long-term xenograft survival, and 4) development or optimization of strategies to screen for and prevent pathogen transmission to recipients. Examples of research topics may include, but are not limited to the following: Elucidation of the cellular and molecular mechanisms of and development of strategies to prevent hyperacute, acute, and chronic xenograft rejection; Characterization of the recipient’s innate and adaptive immune responses to the xenograft; Evaluation of regimens to induce and maintain immune tolerance to xenografts and/or delineation of cellular and molecular mechanisms promoting xenograft tolerance; Development and characterization of strategies to prolong xenograft survival in life-supporting xenotransplantation models; Development of approaches to eliminate or minimize the use of immunosuppressive drugs through genetic modifications of donor organs/tissues/cells, utilization of encapsulation techniques, or other tolerogenic approaches; Characterization of and application of approaches to address differences in the anatomical, physiological, and/or endocrinological features of donor pig organs, tissues, or cells that limit a xenograft’s survival and function in NHP or human decedent recipients; Delineation and study of cross-match differences between pigs and NHPs or humans; Development and testing of tools/approaches to diagnose, monitor, and treat porcine zoonoses in human decedent models; Development and testing of tools/approaches to diagnose, monitor, and treat xenograft rejection; and Development and testing of tools/approaches to diagnose, monitor, and treat causes of xenograft dysfunction other than immunologic rejection. Applications proposing any of the following will be considered non-responsive and will not be reviewed: Pig-to-NHP xenotransplantation studies of any organs, tissues, or cells other than pancreatic islets, kidney, heart, lung, or liver. Small animal models of xenotransplantation, such as rodent models, unless the model is proposed only as an in vivo bioassay of large animal immune function (e.g., trans in vivo delayed type hypersensitivity assay); Clinical trials or clinical/human studies of xenotransplantation; (only preclinical human decedent model research is allowed). Studies of zoonotic agents or infections, except for those studies designed to prevent transmission of, or improve diagnosis, monitoring, or treatment of zoonotic infections in xenograft recipients. Studies focused on HIV/AIDS-related research. Applications that do not include annual milestones. Applications that propose studies in human decedents but do not include a Human Decedent Research Plan. Milestones The research plan must include explicit, detailed, and quantitative annual milestones. These milestones will be used by NIAID program staff to assess annual progress and support funding decisions. Steering Committee Program Directors/Principal Investigators (PD(s)/PI(s)) of awards funded under this program will form a Steering Committee after award. The Steering Committee will serve as the main governing body of the IXCRP. At annual meetings, the Steering Committee will review progress of xenotransplantation projects, provide guidance and recommendations to investigators regarding study implementation and conduct, identify scientific opportunities, emerging needs, and impediments to success, and encourage collaborations among consortium members. The voting members of the Steering Committee will include the PD/PI (contact PI) from each single project U01 award and the PD/PI (contact PI) plus one project leader from each multi-project U19 award. Additional PDs/PIs, Project Leaders, Core Leaders, and the NIH Project Scientist will serve as non-voting Steering Committee members. All IXCRP investigators will be required to accept and implement common guidelines and procedures approved by the Steering Committee. Applicants are encouraged to consider using the following NIAID-supported programs: The Immunology Database and Analysis Portal (ImmPort) The Immunology Database and Analysis Portal (ImmPort) program will provide support for public sharing of research data and experimental protocols of the IXCRP. ImmPort is a NIAID-funded data sharing platform, which has developed templates for data collection, standardization, and sharing from various NIAID-supported research programs. The IXCRP recipients are encouraged to participate with ImmPort in developing data standards for IXCRP-specific data types, where applicable, and be responsible for collecting and submitting data and documents into ImmPort. The IXCRP Steering Committee will provide information, consistent with the goals of the program and NIH policy, regarding research data and experimental protocol sharing within the IXCRP and with the public. The National Swine Resource and Research Center (NSRRC) The Office of Research Infrastructure Programs within the Division of Program Coordination, Planning, and Strategic Initiatives in the Office of the NIH Director supports the National Swine Resource and Research Center (NSRRC), which is co-sponsored by NIAID and the National Heart, Lung, and Blood Institute (NHLBI). The NSRRC was established in 2003 to develop the infrastructure needed to ensure that biomedical investigators across a variety of disciplines have access to critically needed swine models of human health and disease. The purpose of the NSRRC is to provide the biomedical research community enhanced access to critically needed swine models and to develop genetically modified swine when required for studies involving human health and diseases, including xenotransplantation. NIAID encourages IXCRP-funded investigators to submit relevant cell lines and animal models developed under this NOFO to the NSRRC, when applicable. This U01 NOFO is appropriate for applicants that are proposing a single research project while the companion U19 NOFO (RFA-AI-24-020) should be used for investigators proposing a more complex research program involving 2 or more research projects supported by cores. Applicants are strongly encouraged to discuss the proposed research with NIAID staff listed in the Scientific/Research contact well in advance of the application submission deadline. See Section VIII. Other Information for award authorities and regulations.

The purpose of this Notice of Funding Opportunity (NOFO) is to support milestone-driven projects focused on developing and utilizing novel predictive models, assays, tools, and/or platforms based on penetration and efflux of small molecules to facilitate therapeutic discovery for select Gram-negative bacterial pathogens: carbapenem-resistant Acinetobacter, carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant Pseudomonas aeruginosa. A number of Gram-negative bacterial pathogens are associated with the alarming increase in rates of drug resistance in healthcare and community settings. This group includes carbapenem-resistant Acinetobacter , carbapenem-resistant Enterobacterales (CRE), and MDR Pseudomonas aeruginosa that have been designated as “urgent” or “serious” threats in a recent report by the Centers for Disease Control and Prevention (CDC). A significant threat arises from the lack of effective therapeutic options available to treat some of these infections and is exacerbated by the scarcity of novel compounds effective against antimicrobial resistant (AR) and multidrug-resistant (MDR) Gram-negative bacteria in the discovery and development pipeline. In recent years, several public forums (including NIAID-sponsored workshops) identified the lack of understanding of the principles that govern compound penetration into, and efflux out of, Gram-negative bacteria as a key bottleneck for the rational discovery of novel lead therapeutic compounds. The paucity of suitable assays/tools/models to inform structure-activity relationships and guide optimization of whole cell penetration (and efflux avoidance) is reflected in the failure of medicinal chemistry efforts to advance novel chemical classes of compounds with Gram-negative activity. As more Gram-negative bacteria become resistant to antimicrobials and therapeutic options become limited or nonexistent, it becomes imperative to understand and rationalize the principles that allow molecules to penetrate Gram-negative bacteria, while avoiding efflux and overt toxicity toward eukaryotic cells. Therefore, developing new assays, tools, and models is paramount for overcoming this key bottleneck and facilitating the development of novel compounds targeting Gram-negative pathogens. Research Objectives and Scope The objective of this NOFO is to support milestone-driven projects focused on developing and utilizing novel predictive models, assays, tools, and/or platforms aimed at gaining a better understanding of the rules and compound properties that govern the penetration and efflux of drug-like small molecules into Gram-negative bacterial pathogens. This NOFO also supports the preclinical development of novel Gram-negative antibacterial therapeutics based on the tools and models hereby developed. Applications must focus on one or more of the following Gram-negative bacterial pathogens: carbapenem-resistant Acinetobacter, carbapenem-resistant Enterobacterales (CRE), and/or MDR Pseudomonas aeruginosa. Projects should complete assay/tool/model development prior to the end of the third year of the project period and initiate discovery activities to demonstrate its utility in supporting a corresponding medicinal chemistry program to generate a lead chemical series with demonstrated activity against one or more targeted Gram-negative bacteria. This NOFO will also support subsequent preclinical development of a promising lead antibacterial. Given the complex challenges of this research, this initiative encourages applications from multi-disciplinary teams composed of relevant experts in areas such as bacterial physiology, microbiology, bacterial membrane biology, medicinal chemistry, pharmacology, computation, and specialized technologies (microscopy, spectroscopy, electrophysiology, machine learning, etc.), as appropriate. Collaboration with, and utilization of, the NIAID Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB), is recommended for completion of project relevant medicinal chemistry tasks. Close collaboration between academic and industry partners is highly encouraged to optimally combine innovative basic science with drug discovery expertise and proper access to compound libraries more typically available from industry. Examples of assay and model development activities include, but are not limited to: Quantitative cellular (or model system) assays to measure drug penetration and efflux, independent from standard minimum inhibitory concentration (MIC) testing; Innovative quantitative assays to measure drug concentrations in the bacterial cytoplasm and/or periplasmic space; Innovative technologies for dissecting and assessment of the kinetics of drug penetration and efflux from bacteria; and Computational algorithms for describing/predicting physical-chemical properties/guidelines needed by small molecules for optimal Gram-negative penetration and efflux avoidance. Applicants should demonstrate the utility of the developed tools and/or assays to predict and measure potency of candidate therapeutics against Gram-negative targets through one or more approaches. For example, using the developed models and/or assays to guide a medicinal chemistry campaign aimed at producing a novel chemical series with Gram-negative activity; screening existing libraries using the computational algorithms developed as a tool to find compounds with Gram-negative activity; or profiling existing libraries of compounds with known Gram-negative activity. Applications including the following will be considered non-responsive and will not be reviewed: Projects that do not focus on at least one select Gram-negative pathogen (carbapenem-resistant Acinetobacter, carbapenem-resistant Enterobacterales, or MDR Pseudomonas aeruginosa); Projects focused only on Gram-positive bacteria or Mycobacterium tuberculosis; Projects that do not focus on penetration and efflux of small molecules; Applications not containing a Milestone and Timeline attachment; Applications proposing Clinical trials; and Research on HIV/AIDS.

The purpose of this notice of funding opportunity (NOFO) is to solicit applications to participate in the Immunobiology of Xenotransplantation Cooperative Research Program (IXCRP), a multi-center program dedicated to resolving immunologic and physiologic barriers to safe and efficacious xenotransplantation using preclinical pig to nonhuman primate (NHP) or human decedent models of pancreatic islet, kidney, heart, lung, or liver xenotransplantation. Transplantation is often the preferred or only therapy for end-stage organ disease. In 2023, 46,630 organ transplants were performed in the United States. In addition, transplantation of pancreatic islets offers a potential therapy for individuals with type 1 diabetes whose disease is not effectively managed with exogenous insulin. Unfortunately, with over 103,500 adults and children on the United Network for Organ Sharing (UNOS) waiting list, those in need of a transplant greatly exceed the number of available organs. It is estimated that 20 people on average die each day waiting for a transplant. Xenotransplantation offers a potential interim or definitive solution to the severe shortage of human organs and pancreatic islets. Pigs are the primary species of interest as xenograft donors due to their favorable reproductive capacity and anatomical and physiological similarities to humans. However, there are multiple barriers to successful clinical xenotransplantation, including immunologic rejection of non-human organs and tissues by the human immune system, physiological differences between non-human and human molecules that prevent proper functioning of various biochemical pathways, and potential transmission of zoonoses. To address these challenges, the IXCRP was established by the National Institute of Allergy and Infectious Diseases (NIAID) in 2005 with a co-fund for type 1 diabetes from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (RFA-AI-04-042). Subsequently, in 2010, the program was renewed solely by NIAID (RFA-AI-09-035), in 2015 (RFA-AI-14-047 and RFA-AI-14-048), and in 2020 (RFA-AI-19-042 and RFA-AI-19-043).. IXCRP investigators and other researchers in the field have made significant advances over the past two decades, and NIAID is committed to support this challenging area of research. Historically, the most significant hurdle to successful xenotransplantation was hyperacute rejection caused by preformed, xenoreactive naturally-occurring antibodies (XNA) that destroy the xenograft within hours post-transplant. The primary target of XNA is a carbohydrate epitope, galactose-alpha-(1,3)-galactose (Gal), which is not present in humans and Old World NHPs. To overcome this hurdle, two decades ago, the enzyme responsible for terminally linking Gal onto oligosaccharide chains, alpha-1,3 glycosyltransferase (GT), was knocked out in genetically modified pigs. Xenografts from GT knockout (GTKO) pigs elicit substantially less severe hyperacute rejection in NHPs. Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene knockouts and mutations to beta-1,4-N-acetyl-galactosaminyltransferase 2 (B4GALNT2) were similarly engineered to reduce reactivity to other notable XNA to pig carbohydrate antigens, namely N-glycolylneuraminic acid-modified glycans and SDa swine blood group antigen, respectively. Over the last decade, application of CRISPR-Cas 9 technology combined with somatic cell nuclear transfer cloning has significantly accelerated the pace of multi-gene modification and donor pig production. Additional genetic modifications, most on the GTKO background, were developed to address key species-to-species incompatibilities and create more human-like organs. These include the insertion of human complement regulatory proteins to minimize the deleterious effects of the complement cascade in antibody-mediated rejection, human thrombomodulin and/or tissue factor pathway inhibitor to overcome coagulation pathway dysfunction, and human anti-inflammatory and/or immune suppressive genes to reduce immune activation contributing to graft rejection. These strategies have dramatically reduced the frequency and severity of hyperacute rejection and have prolonged survival in pig-to-NHP xenotransplantation models for up to 4 years. Success in prolonging xenograft survival in the pig-to-NHP model allows more in-depth investigation of the remaining immunologic and physiologic issues that must be addressed in order to achieve safe and efficacious clinical xenotransplantation. These include physiologic differences that influence xenograft function and long-term survival, and risks associated with zoonoses. Transmission of pathogenic zoonoses to a human recipient and, potentially, the general population is a concern. To reduce this risk, animals used for xenotransplantation are bred in specific-pathogen-free conditions, weaned early or caesarian-derived, and routinely screened to eliminate most, if not all, known zoonotic agents. Porcine Cytomegalovirus (PCMV) is a swine pathogen known to have deleterious effects on xenograft survival. In the first human patient to receive a cardiac xenotransplant, conventional testing failed to detect latent PCMV in the donor pig and the virus reactivated post-transplant. The extent to which PCMV reactivation contributed to the patient’s death is unknown; however, this event underscores the need for sensitive and reliable assays to detect both latent and active infection with PCMV. Porcine endogenous retroviruses (PERV), another potential zoonotic threat, were successfully inactivated in a line of pigs through a combination of CRISPR-Cas9 gene-editing and somatic cell nuclear transfer, further highlighting the potential of these technologies to both protect against immunologic attack and reduce the risk of zoonoses. The field of xenotransplantation has recently witnessed an expansion in research models beyond NHP recipients to include an evaluation of safety, feasibility, and short-term outcomes (2 – 60 days) in humans declared to have irreversible loss of brain function (individuals with brain death, also referred to as human decedents) maintained on cardiopulmonary support. These experiments, using varying genetically modified pig hearts and kidneys transplanted into human decedents whose organs were declined for allotransplantation based on organ quality, have demonstrated early hemodynamic stability, an absence of hyperacute rejection, and basic organ functionality under immunosuppression. No chimerism or transmission of porcine retroviruses were detected; however, many of these experiments have demonstrated thrombotic microangiopathy and/or antibody-mediated injury. As of the time of this writing, medical teams that include IXCRP-funded investigators have performed two pig-to-human orthotopic heart transplants under expanded access (compassionate use) authorization from the FDA. The two xenograft recipients expired at 8 and 6 weeks, respectively. These initial clinical xenotransplants demonstrated good early xenograft function but also highlighted fundamental gaps in our knowledge of 1) critical pathways leading to inflammation and graft failure, 2) best practices for zoonotic viral surveillance and treatment, 3) optimal design of the donor pig, and 4) postoperative immunosuppression regimen. These knowledge gaps must be addressed prior to broader clinical translation. Scope and Research Objectives The re-issue of the IXCRP will support a research program comprised of two or more research projects centered around preclinical NHP and/or human decedent models of porcine pancreatic islet, kidney, heart, lung, or liver xenotransplantation. The research objectives must address one or more of the remaining key immunologic and physiologic barriers to achieving safe and efficacious xenotransplantation, including issues affecting engraftment, survival, and function of xenografts. Research foci may include 1) development or optimization of the models themselves, including genetic modifications of the pig-donor to address FDA concerns, as well as refinement of surgical xenotransplantation techniques, 2) development or optimization of the immunosuppression (IS) regimen to prevent rejection and minimize toxicity, 3) characterization and resolution of physiological and immunological barriers to long-term xenograft survival, and 4) development or optimization of strategies to screen for and prevent pathogen transmission to recipients. Examples of research topics may include, but are not limited to the following: Elucidation of the cellular and molecular mechanisms of and development of strategies to prevent hyperacute, acute, and chronic xenograft rejection; Characterization of the recipient’s innate and adaptive immune responses to the xenograft; Evaluation of regimens to induce and maintain immune tolerance to xenografts and/or delineation of cellular and molecular mechanisms promoting xenograft tolerance; Development and characterization of strategies to prolong xenograft survival in life-supporting xenotransplantation models; Development of approaches to eliminate or minimize the use of immunosuppressive drugs through genetic modifications of donor organs/tissues/cells, utilization of encapsulation techniques, or other tolerogenic approaches; Characterization of and application of approaches to address differences in the anatomical, physiological, and/or endocrinological features of donor pig organs, tissues, or cells that limit a xenograft’s survival and function in NHP or human decedent recipients; Delineation and study of cross-match differences between pigs and NHPs or humans; Development and testing of tools/approaches to diagnose, monitor, and treat porcine zoonoses in human decedent models; Development and testing of tools/approaches to diagnose, monitor, and treat xenograft rejection; and Development and testing of tools/approaches to diagnose, monitor, and treat causes of xenograft dysfunction other than immunologic rejection. Applications proposing any of the following will be considered non-responsive and will not be reviewed: Pig-to-NHP xenotransplantation studies of any organs, tissues, or cells other than pancreatic islets, kidney, heart, lung, or liver. Small animal models of xenotransplantation, such as rodent models, unless the model is proposed only as an in vivo bioassay of large animal immune function (e.g., trans in vivo delayed type hypersensitivity assay); Clinical trials or clinical/human studies of xenotransplantation; (only preclinical human decedent model research is allowed). Studies of zoonotic agents or infections, except for those studies designed to prevent transmission of, or improve diagnosis, monitoring, or treatment of zoonotic infections in xenograft recipients. Studies focused on HIV/AIDS-related research Applications that do not include annual milestones. Applications that propose studies in human decedents but do not include a Human Decedent Research Plan. Structure of the IXCRP Administrative Core: Each application will include an Administrative Core to manage and coordinate all activities to ensure project timelines and objectives are met. The Administrative Core will include a Program Management Plan that will guide its operations and activities. This Core will be responsible for carrying out activities described in the Data Management and Sharing Plan. The Administrative Core will also be responsible for organizing an annual programmatic meeting for all investigators and NIAID staff. Scientific Core: Scientific Cores are optional and may be included to provide IXCRP investigators with core resources and/or facilities that are essential for the activities of two or more Research Projects. Scientific Core activities must not overlap with each other or with the activities of a Research Project. The Scientific Core may not conduct research independent of the served Research Project. Research Projects: Applications will propose at least two synergistic Research Projects that meet the goals of the initiative to resolve the immunologic and physiologic barriers to safe and efficacious xenotransplantation using preclinical pig to nonhuman primate (NHP) or human decedent models of pancreatic islet, kidney, heart, lung, or liver xenotransplantation. Milestones The research projects must include explicit, detailed, and quantitative annual milestones. These milestones will be used by NIAID program staff to assess annual progress and support funding decisions. Steering Committee Program Directors/Principal Investigators (PD(s)/PI(s)) of awards funded under this program will form a Steering Committee after award. The Steering Committee will serve as the main governing body of the IXCRP. At annual meetings, the Steering Committee will review progress of xenotransplantation projects, provide guidance and recommendations to investigators regarding study implementation and conduct, identify scientific opportunities, emerging needs, and impediments to success, and encourage collaborations among consortium members. The voting members of the Steering Committee will include the PD/PI (contact PI) from each single project U01 award and the PD/PI (contact PI) plus one project leader from each multi-project U19 award. Additional PDs/PIs, Project Leaders, Core Leaders, and the NIH Project Scientist will serve as non-voting Steering Committee members. All IXCRP investigators will be required to accept and implement common guidelines and procedures approved by the Steering Committee. Applicants are encouraged to consider using the following NIAID-supported programs: The Immunology Database and Analysis Portal (ImmPort) The Immunology Database and Analysis Portal (ImmPort) program will provide support for public sharing of research data and experimental protocols of the IXCRP. ImmPort is a NIAID-funded data sharing platform, which has developed templates for data collection, standardization, and sharing from various NIAID-supported research programs. The IXCRP recipients are encouraged to participate with ImmPort in developing data standards for IXCRP-specific data types, where applicable, and be responsible for collecting and submitting data and documents into ImmPort. The IXCRP Steering Committee will provide information, consistent with the goals of the program and NIH policy, regarding research data and experimental protocol sharing within the IXCRP and with the public. The National Swine Resource and Research Center (NSRRC) The Office of Research Infrastructure Programs within the Division of Program Coordination, Planning, and Strategic Initiatives in the Office of the NIH Director supports the National Swine Resource and Research Center (NSRRC), which is co-sponsored by NIAID and the National Heart, Lung, and Blood Institute (NHLBI). The NSRRC was established in 2003 to develop the infrastructure needed to ensure that biomedical investigators across a variety of disciplines have access to critically needed swine models of human health and disease. The purpose of the NSRRC is to provide the biomedical research community enhanced access to critically needed swine models and to develop genetically modified swine when required for studies involving human health and diseases, including xenotransplantation. NIAID encourages IXCRP-funded investigators to submit relevant cell lines and animal models developed under this NOFO to the NSRRC, when applicable. The current U19 NOFO is appropriate for investigators proposing a complex research program involving 2 or more research projects supported cores while the companion U01 NOFO (RFA-AI-24-019) should be used for applicants that are proposing a single research project. Applicants are strongly encouraged to discuss the proposed research with NIAID staff listed in the Scientific/Research contact well in advance of the application submission deadline. See Section VIII. Other Information for award authorities and regulations.

With this solicitation, OJJDP seeks to enhance and expand mentoring services for children and youth impacted by opioids and other substance misuse. This program supports mentoring programs to reduce juvenile delinquency, substance misuse, and problem and high-risk behaviors such as truancy. This program supports the implementation and delivery of mentoring services to youth who are currently misusing or dependent on substances (including opioids, stimulants, and other licit or illicit substances), youth at risk for misusing substances, and youth with family members who are currently misusing or dependent on substances. Mentoring services can be one-to-one, group, peer, or a combination. Category 1: Mentoring Strategies for Youth Affected by Opioid and Other Substance Misuse (Project Sites) Eligible organizations are those that have been in existence for at least 3 years at the time of application, and have been directly delivering a structured mentoring program model. Category 2: Statewide and Regional Mentoring Strategies for Youth Affected by Opioid and Other Substance Misuse

The main objective of this NOFO is to foster development and testing of technologies adaptable to aging-related changes in older adults (aged 65 years or older) with T1D to improve diabetes management and quality of life. Older adults may have increased vulnerability to hypoglycemia, cognitive impairment and/or multiple co-morbidities which may affect the risks and benefits of these technologies in this population. Projects will be funded to a) develop and test new technologies and b) to adapt and test existing technologies. It is expected that aging-adaptive diabetes technologies that address barriers for use among older adults with T1D will improve usability, adoption and adherence decreasing the risk of hypoglycemia (and hypoglycemia unawareness) while enhancing glycemic control, facilitating better diabetes management, and improving quality of life for these individuals and their caregivers.

The U.S. Embassy Baghdad Public Diplomacy Section (PD Section), on behalf of U.S. Mission Iraq, is pleased to announce that funding is available through its Public Diplomacy Small Grants Program. This is an Annual Program Statement, outlining our funding priorities, the strategic themes we focus on, and the procedures for submitting requests for funding. Applications for programs are accepted on a rolling basis until the deadline of September 1, 2024. A grant review committee will review outstanding applications on a rolling basis. This Notice of Funding Opportunity covers the whole of Iraq, to include the Iraqi Kurdistan Region (IKR). Please carefully follow all instructions attached. Purpose of Small Grants: The Embassy PD Section invites proposals for programs that strengthen cultural ties between the United States and Iraq through cultural and exchange programming that highlights shared values and promotes bilateral cooperation. All programs must include an American cultural element, or connection with American expert/s, organization/s, or institution/s in a specific field that will promote increased understanding of U.S. policy and perspectives. Examples of Projects include, but are not limited to: Academic and professional lectures, seminars, and speaker programs. Youth leadership programs. Professional and academic exchanges and non-research projects. Entrepreneurship and innovation in technological or other fields. Priority Programming Areas: Strengthening Governance, Democracy, and the Rule of Law Strengthening Civil Society and Promoting Civic Engagement Enhancing Professionalism in the Media Combatting Disinformation Countering Violent Extremism Promoting Innovation and Entrepreneurship Empowering Women, Youth, or Religious and Ethnic Minorities Fostering U.S.-Iraqi Cultural Ties Protecting and Preserving Iraqi Cultural Heritage

This Notice of Funding Opportunity (NOFO) requests applications to explore human pancreatic tissues and the immune compartment for the discovery of specific signaling or processing pathways that may contribute to the asymptomatic phase of T1D, the discovery of early biomarkers of T1D pathogenesis, the development of diagnostic tools for the detection and staging of early T1D in at-risk or recently-diagnosed individuals, and/or the identification and biological validation of therapeutic targets for the development of preventative or early treatment strategies. Successful applicants will join the Consortium on Beta Cell Death and Survival (CBDS), whose mission is to better define and detect the mechanisms of beta cell stress and destruction central to the development of T1D in humans, with the long-term goal of protecting the residual beta cell mass in T1D patients as early as possible in the disease process, and of preventing the progression to autoimmunity. The CBDS is part of a collaborative research framework, the Human Islet Research Network (HIRN, https://hirnetwork.org/), whose overall mission is to support innovative and collaborative translational research to understand how human beta cells are lost in T1D, and to find innovative strategies to protect and replace functional beta cell mass in humans. This NOFO will only support studies with a primary focus on increasing our understanding of human disease biology (as opposed to rodent or other animal models). This NOFO will not accept applications proposing a clinical trial.

The INFRA program, part of the MPDG, allocates $2.7 billion towards competitive grants for significant multimodal freight and highway projects that aim to improve the safety, efficiency, and reliability of freight and people movement across rural and urban areas. It focuses on projects that enhance economic benefits, reduce congestion, increase resiliency, and improve critical freight movements. The program encourages applications that address supply chain bottlenecks and are of national or regional significance. The application deadline is May 6, 2024.

The purpose of the Disability and Rehabilitation Research Projects (DRRP) is to plan and conduct research, demonstration projects, training, and related activities, including international activities, to develop methods, procedures, and rehabilitation technology that maximize the full inclusion and integration into society, employment, independent living, family support, and economic and social self-sufficiency of individuals with disabilities, especially individuals with disabilities who have the greatest support needs, and to improve the effectiveness of services authorized under the Rehabilitation Act of 1973, as amended (Rehabilitation Act). Under this particular DRRP priority, the grantee must conduct research toward maternal health services or interventions to improve pregnancy outcomes among women with long-term disabilities. NIDILRR plans to make one award under this opportunity in FY 2024. The grant will have a 60-month project period, with five 12-month budget periods.

The National Academies of Sciences, Engineering, and Medicine’s Gulf Research Program (GRP) is inviting proposals for its "Building the Next Generation of STEMM Leaders in the Field of Environmental Justice" initiative. This grant opportunity is designed to support projects that develop and implement programs cultivating future STEMM leaders in Environmental Justice (EJ). The GRP's mission, as evident in this program, aligns with fostering scientific literacy and addressing critical environmental challenges through education and mentorship. The grant aims to raise awareness, expand understanding, and empower young people to apply STEMM disciplines to explore the relationship between environmental hazards and their effects on community health and resilience. The primary beneficiaries of this program are young people in grades 9-12, particularly those from communities affected by environmental inequalities in the United States Gulf of Mexico region. The impact goal is to increase the number of young people in this region who pursue studies and careers in STEMM disciplines within the field of Environmental Justice. The program specifically encourages collaborations with nonprofit or community-based organizations that have a history of working with children and youth, especially underrepresented or underserved populations such as racial/ethnic minorities, tribal youth, LGBTQ+ youth, students with low socio-economic status, children with disabilities, first-generation immigrants, and students from rural or remote areas. The core focus of this funding opportunity is on education and mentorship. Projects should provide youth with opportunities to learn about and apply STEMM principles in examining environmental hazards and their impact on communities. Activities can take place in both formal and informal educational settings, but must target 9th-12th graders and complement formal education standards. The GRP prioritizes proposals that foster the development of scientific and environmental literacy, skills, and competencies crucial for cultivating the next generation of EJ leaders. Expected outcomes include increased awareness and understanding among youth regarding environmental hazards and their effects on communities, as well as enhanced capacity for youth to pursue STEMM studies and/or careers in Environmental Justice. The GRP anticipates a measurable increase in the number of young people in the Gulf of Mexico region engaging with STEMM disciplines related to EJ. This grant operates with a strategic priority of building human capacity and fostering a more equitable and resilient future by empowering youth to address environmental challenges. The theory of change behind this initiative is that by investing in early education and mentorship in STEMM and EJ, the GRP can create a pipeline of informed and capable leaders who will contribute to solving complex environmental issues in vulnerable communities.

To implement a project aimed at advancing U.S. foreign policy and national security priorities by supporting initiatives that make decision-making structures and processes in fragile, conflict, or crisis-affected contexts more reflective of and responsive to the needs and perspectives of partner states to ensure strategic trade control systems meet international standards and by engaging on bilateral, regional and multilateral levels with foreign governments to aid in the establishment of independent capabilities to regulate transfers of weapons of mass destruction, WMD-related items, conventional arms, and related dual-use items, and to detect, interdict, investigate, and prosecute illicit transfers of such items.

This funding opportunity supports research aimed at improving primary care delivery and outcomes, particularly focusing on enhancing access, equity, and the overall quality of healthcare for patients and communities.

Under this particular DRRP funding opportunity, applicants must propose to (1) conduct research on the air travel experiences and outcomes of people with disabilities; (2) conduct research on practices, policies, and systems that shape air travel experiences and outcomes among people with disabilities; and (3) conduct knowledge translation activities to promote air travel accessibility and positive air travel experiences and outcomes among people with disabilities. The grant will have a 60-month project period, with five 12-month budget periods.

This Notice of Funding Opportunity (NOFO) invites applications for Diabetes Research Centers (DRCs) that are designed to support and enhance the national research effort in diabetes, its complications, and related endocrine and metabolic diseases. The purpose of this Centers program is to bring together basic and clinical investigators to enhance communication, multidisciplinary collaboration, and effectiveness of ongoing research in Diabetes Research Center topic areas. By providing shared access to specialized technical resources (research cores) and supporting a Pilot and Feasibility Program (P and F), DRCs are intended to create an environment that provides the capability for accomplishments greater than those that would be possible by individual research project grant support alone. New Center programs that bring in diverse perspectives, propose unique scientific themes, or provide innovative resources are encouraged. Emphasis will be placed on Center programs that propose enhanced synergies with other NIDDK-funded programs as well as providing a rich mentoring environment for future diabetes researchers. This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn. Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP guidance material.

The Office of Refugee Resettlement (ORR), within the Administration for Children and Families (ACF), announces the availability of funds for the National Refugee Leadership and Lived Experience Council (NRLLEC) Program. The NRLLEC is a new program funded by the Office of Refugee Resettlement (ORR) that designs, implements, evaluates, and promotes national-level councils consisting of refugees and other ORR-eligible populations who have resettled into communities throughout the United States within the last five years. The NRLLEC Program will facilitate a National Young Adult Leadership Council comprised of members ages 18 to 24 every year for three years, as well as two additional councils with thematic focus to be determined in consultation with ORR. The NRLLEC Program will design, implement, evaluate, and promote five councils during the three-year project period. The programs primary goal is to positively impact the lives of council members and their refugee and larger communities by building council members capacity to serve as leaders. In addition, ORR recognizes that its engagement with these groups will enhance its ability to gather information from individual members firsthand about their lived experiences integrating into the United States. This will help inform ORR and its recipient network about how to best meet refugee needs through enhancing or changing ORR guidance, programming, and future councils. The NRLLEC Program will foster inclusivity, with council members attuned to the diversity, demographics, needs, and viewpoints of ORRs eligible population (https://www.acf.hhs.gov/orr/programs/refugees/factsheets). The NRLLEC Program will not seek consensus advice from council members.

Section 2391(d) of Title 10, United States Code (10 U.S.C. 2391(d)), authorizes the Secretary of Defense to make grants, conclude cooperative agreements, and supplement funds available under Federal programs administered by agencies other than the Department of Defense to assist State and local governments to address deficiencies in community infrastructure supportive of a military installation. Community infrastructure projects are transportation projects, community support facilities (e.g., schools, hospitals, police, fire, and emergency response), and utility infrastructure projects (e.g., water, wastewater, telecommunications, electric, gas, etc.) that are located off of a military installation or on property under the jurisdiction of a Secretary of a military department that is subject to a real estate agreement (including a lease or easement), and are owned by a state or local government or a not-for-profit, member-owned utility service. This Notice identifies the criteria established for the selection of community infrastructure projects. Proposals will be competitively scored across these criteria, identified in Section E., paragraph 1. of this Notice. Program funding at $100 million is available and will expire if not obligated prior to the close of business on September 30, 2024. Project proposals must include a letter of support from the local installation commander representing the installation benefitting from the proposed project. Letters of support must, at a minimum, indicate the benefitting installations need for the project, willingness to support the civilian execution of the project to the extent practicable, including assisting the Office of Local Defense Community Cooperation with technical review and execution of any required National Environmental Policy Act documentation for the proposed project, and, where applicable, indicate if the proposed project is defense-related critical infrastructure. For proposals for projects that will contribute to the training of cadets enrolled in an independent program at a covered educational institution, the letter of support must include the support of an installation commander for an installation benefitting from the proposed project, regardless of the distance between the covered educational institution and the installation benefitting from the project.