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Diseases Network (UDN) building upon the NIH Intramural Research Programs Undiagnosed Diseases Program (NIH-UDP). Responsive applications will propose to investigate the underlying genetics, biochemistry and/or pathophysiology of newly diagnosed diseases in association with the respective gene variant(s) identified through the UDN. In recent years, gene function studies combined with genetic and genomic analyses and metabolic studies have greatly improved diagnoses of these very rare diseases and advanced scientific knowledge of the underlying pathogenesis. This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact.

This Funding Opportunity Announcement (FOA) invites applications that seek to enhance existing transcriptome and proteome data sets by revealing oscillatory patterns of gene expression in aging and in Alzheimer's disease (AD), by uncovering their molecular significance, and by identifying rhythmic gene and/or protein profiles associated with the risk for AD.

This Funding Opportunity Announcement (FOA) invites applications that seek to enhance existing transcriptome and proteome data sets by revealing oscillatory patterns of gene expression in aging and in Alzheimer's disease (AD), by uncovering their molecular significance, and by identifying rhythmic gene and/or protein profiles associated with the risk for AD. Outcomes of this research may suggest novel opportunities for translational research to allow development of individualized, optimized treatment based on circadian phase and amplitude.

MOD invites all qualified scientists with faculty appointments or the equivalent, at universities, hospitals and research institutions (not for profit or profit), to submit applications for research grants relevant to our mission. This encompasses basic biological processes governing differentiation and development, genetics and genomics of these processes, clinical studies, reproductive health and environmental toxicology, and social and behavioral studies concerning cognitive and behavioral risks that affect outcomes of pregnancy, the perinatal period, and subsequent child development. Applications will be directed to one of three committees whose respective foci are:    * Cell Lineage and Differentiation  * Gene Discovery and Translational Medicine  * Social and Behavioral Sciences. This involves family units and includes genes, toxicants, social  determinants that adversely affect language or behavior, especially if involving premature  infants or children with birth defects.

The purpose of this Funding Opportunity Announcement (FOA) is to establish a Model Organisms Screening Center for evaluating the pathogenicity and function of approximately 200 gene variants per year identified through the Undiagnosed Diseases Network (UDN). Responsive applications will propose to establish a screening platform involving at a minimum Drosophila and zebrafish models; the screening pipeline may include additional small animal models or cell-based assays, as appropriate, to analyze the function of UDN gene variants in the context of the respective UDN patient's disease phenotype. This initiative is funded through the NIH Common Fund which supports cross-cutting programs that are expected to have exceptionally high impact.

The Division of Integrative Organismal Systems (IOS) recognizes that a lack of methods for analysis of gene function represents an obstacle to progress in a range of diverse non-model organisms. These organisms are important for understanding numerous basic science questions in organismal biology as funded through the Division's core programs. Enabling Discovery through Genomic Tools (EDGE) is designed to provide support for development of tools, approaches and infrastructure necessary for direct tests of cause and effect hypotheses between gene function and phenotypes in diverse plants, animals, microbes, viruses and fungi for which these methods are presently unavailable. Such approaches are essential to advance understanding of the genomes-to-phenomes relationship, an area relevant to Understanding the Rules of Life: Predicting Phenotype , one of the 10 Big Ideas for future NSF investment.

GSK is seeking rapid, point of care analytical tests for gene therapy products that can go from sample to result within 2 hours   Tests should work with human cells at a concentration of 1x106 - 1x108 cells per mL in growth media. They should characterize / quantify the populations of cell immunophenotypes in the sample.   Lab tests are welcome. GSK would be especially interested in analytical techniques that could be carried out at or close to the patient's bedside.

Chemical modifications of protein, DNA and RNA nucleoside moieties play critical roles in regulating gene expression. Emerging evidence suggests RNA modifications have substantive roles in multiple basic biological processes. Epitranscriptomics can be defined as the aggregate suite of functional biochemical modifications to the transcriptome within a cell. Recent studies in yeast, Drosophila, rodent and human models demonstrate that stressors can induce RNA modifications, with specific reprogramming of some regulatory RNAs. The NIEHS seeks to solicit innovative, mechanistic research applications that are focused on how environmental exposures are associated and involved with the functional activities of RNA modifications and pathways that may be modified or misregulated, associated with adverse health outcomes and/or be useful as biomarkers of exposure and/or exposure-induced pathologies. The study of functional chemical RNA modification has identified important emerging roles in cellular regulation and gene expression. However, the impact of environmental exposures on functional RNA modifications has been relatively understudied and may present a new mechanism for enhanced understanding the relationships between exposures and the development of complex human diseases. The NIEHS will use the R01 mechanism to support hypothesis driven research using approaches that incorporate principles of toxicology with RNA modification biological and/or chemical expertise and utilizes state of the art technologies.

The purpose of this Funding Opportunity Announcement (FOA) is to invite applications for short-term, proof-of-principle research projects that will provide preliminary data for a future FOA aimed at the development of new models that emulate human visual system anatomy, physiology and disease processes. The model system might involve specific defects generated by transgenic gene insertion and/or deletion, gene editing, chemical/physical means, and/or other approaches to emulate characteristics of human disease or create defects amenable to cell-replacement and/or regenerative therapy. Using non-human primates or other cone-dominant species that are more representative of the anatomy and physiology of the human retina are highly encouraged. Other biological models are acceptable provided they meet the overall objectives of the FOA.

The importance of genetic susceptibility in inflammatory bowel diseases (IBD) has been established in the last decade and risk genes have been identified. However, the lack of complete gene penetrance and the rapid rise of IBD incidence in certain geographic regions suggest that the interaction between genetic and environmental factors contribute to IBD. Several environmental risk factors including drugs (antibiotics), viruses, psychological stress, air pollutants, diet and chemicals have been explored but the data is still inconclusive.

This Funding Opportunity Announcement (FOA) supports the optimization of potential therapeutic Biotechnology Products and Biologics (e.g., peptides, proteins, oligonucleotides, gene and cell therapies) for disorders identified under the NINDS mission. This track supports the further characterization and optimization of therapeutic lead(s) that showed promise as a potential therapeutic agent as evidenced by convincing animal proof-of-concept studies. Therefore, at the end of this funding period, successful projects will have delivered and optimized therapeutic candidate with demonstrated bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and should be eligible for entry into the CREATE Bio Development track. The CREATE Bio Development track is a later stage program focused on the development of optimized therapeutic candidates through Investigational New Drug (IND)-enabling studies and submission of an IND package to the Food and Drug Administration (FDA). This Funding Opportunity Announcement (FOA) supports the optimization of potential therapeutic Biotechnology Products and Biologics (e.g., peptides, proteins, oligonucleotides, gene and cell therapies) for disorders identified under the NINDS mission. This track supports the further characterization and optimization of therapeutic lead(s) that showed promise as a potential therapeutic agent as evidenced by convincing animal proof-of-concept studies. Therefore, at the end of this funding period, successful projects will have delivered and optimized therapeutic candidate with demonstrated bioactivity, stability, manufacturability, bioavailability, in vivo efficacy and should be eligible for entry into the CREATE Bio Development track. The CREATE Bio Development track is a later stage program focused on the development of optimized therapeutic candidates through Investigational New Drug (IND)-enabling studies and submission of an IND package to the Food and Drug Administration (FDA).

The purpose of this Funding Opportunity Announcement (FOA) is to provide a Model Organisms Screening Center for Phase II of the Undiagnosed Diseases Network (UDN). The Center will evaluate the pathogenicity and function of approximately 200 gene variants per year identified through the UDN. Responsive applications will propose to establish a screening strategy for selecting the most informative variants for analysis, and a research platform involving at a minimum Drosophila and zebrafish models. The screening pipeline may include additional small animal models or cell-based assays, as appropriate, to analyze the function of UDN gene variants in the context of the respective UDN participants disease phenotype. This initiative is funded through the NIH Common Fund which supports cross-cutting programs that are expected to have exceptionally high impact.

The purpose of this FOA is to establish expert panels that will select genes and genomic variants associated with diseases or conditions of high priority to participating NIH Institutes and Centers (ICs) and systematically determine their clinical significance for diagnosis and treatment of these diseases or conditions. The Genomic Expert Curation Panels funded through this FOA are r?e?q?u?i?r?e?d to utilize the NHGRI Clinical Genomics Resource (ClinGen) and the NCBI ClinVar procedures, interfaces, tools and informatics infrastructure to determine the strength of evidence supporting the clinical significance of the selected genes and variants that will support development of clinical practice guidelines.

The purpose of this Funding Opportunity Announcement (FOA) is to provide a Model Organisms Screening Center for Phase II of the Undiagnosed Diseases Network (UDN).  The Center will evaluate the pathogenicity and function of approximately 200 gene variants per year identified through the UDN. Responsive applications will propose to establish a screening strategy for selecting the most informative variants for analysis, and a research platform involving at a minimum Drosophila and zebrafish models. The screening pipeline may include additional small animal models or cell-based assays, as appropriate, to analyze the function of UDN gene variants in the context of the respective UDN participant's disease phenotype. This initiative is funded through the NIH Common Fund which supports cross-cutting programs that are expected to have exceptionally high impact.

The purpose of this funding opportunity announcement (FOA) is to stimulate clinical research that applies a social genomics approach to chronic wound risk, presence, progression, and healing. The field of social genomics focuses on how the social environment influences gene expression, and how this gene expression may in turn impact health outcomes. Chronic wounds (e.g., diabetic ulcers, venous or arterial ulcers) are multidimensional and, as such, there is benefit to a holistic approach that goes beyond a focus on the wound (i.e., repairing the skin and underlying tissue) to include an approach that focuses on the person with the wound. A better understanding of social environmental factors (positive and negative) and associated molecular mechanisms is needed to advance therapeutic strategies aimed at reducing chronic wound risk in addition to improving healing outcomes and quality of life.

The purpose of this FOA is to stimulate development of translation-enabling models for evaluating survival and integration of regenerated photoreceptors (PRCs) and retinal ganglion cells (RGCs) in model systems that are closer to human visual anatomy, function and/or disease than current models. The development of these models, tools, devices, novel therapies and/or other resources is expected to provide a resource to vision researchers developing cell-replacement therapies for visual system diseases and disorders. This FOA seeks to develop models that emulate critical aspects of a human blinding disease that might be amenable to regenerative therapy. The model system might involve specific defects generated by transgenic gene insertion and/or deletion, gene editing, chemical/physical means, and/or other approaches to emulate characteristics of human disease or create defects amenable to cell-replacement therapy. Model systems using non-human primates or other cone-dominant species that are more representative of the anatomy and physiology of the human retina are highly encouraged. Other biological models are acceptable provided they meet the overall objectives of the FOA.

The Division of Integrative Organismal Systems (IOS) continues to support the Enabling Discovery through GEnomic Tools (EDGE) program, previously a component of the IOS Core Programs solicitation (NSF 16-505). EDGE is designed to provide support for research addressing current impediments to research progress in organismal biology. In particular, the ability to directly test gene function is essential to improve understanding of the genomes-to-phenomes relationship, an area relevant to Understanding the Rules of Life, one of 10 Big Ideas for future NSF investment (www.nsf.gov/about/congress/reports/nsf_big_ideas.pdf). EDGE projects should focus on development of functional genomic tools, approaches, and associated infrastructure to enable direct tests of hypotheses about gene function in diverse organisms for which such tools and infrastructure are presently unavailable

1. Basic Science of Gene Therapy for Hemophilia * Basic science, tropism, transduction efficiency & tolerability of Adeno associated virus (AAV) * AAV antibody seroprevalence, titer- assessment, reduction & tolerance * Role of immunosuppression in managing immune response and potential retreatment * Effect of Gene Therapy on liver biology 2. Basic Science of TFPI & Anti-TFPI Monoclonal Antibodies * Basic biology of TFPI interactions with Protein C, ATIII & Protein S * Cross talk among regulators (e.g., Protein S being a co-factor for both Protein C and TFPI) * Role of different TFPI pools in regulation of coagulation * Impact of concomitant treatments (especially antifibrinolytics) added to anti-TFPI on the physiology of hemostasis * Note: Pfizer will not supply study drug 3. Burden of disease: Clinical Hemophilia A and B * Natural history of hemophilia and adherence to current standard of care * Arthropathy: presence, development, clinical burden & joint damage in hemophilia * Patient experiences with hemophilia, treatment preferences and quality of care * Quality of Life/Work analysis and cost of care in Hemophilia

The Law & Science Program considers proposals that address social scientific studies of law and law-like systems of rules, as well as studies of how science and technology are applied in legal contexts. The Program is inherently interdisciplinary and multi-methodological. Successful proposals describe research that advances scientific theory and understanding of the connections between human behavior and law, legal institutions, or legal processes; or the interactions of law and basic sciences, including biology, computer and information sciences, STEM education, engineering, geosciences, and math and physical sciences. Scientific studies of law often approach law as dynamic, interacting with multiple arenas, and with the participation of multiple actors. Fields of study include many disciplines, and often address problems including, though not limited, to: Crime, Violence, and Policing Cyberspace Economic Issues Environmental Science Evidentiary Issues Forensic Science Governance and Courts Human Rights and Comparative Law Information Technology Legal and Ethical Issues related to Science Legal Decision Making Legal Mobilization and Conceptions of Justice Litigation and the Legal Profession Punishment and Corrections Regulation and Facilitation of Biotechnology (e.g., Gene Editing, Gene Testing, Synthetic Biology) and Other Emerging Sciences and Technologies Use of Science in the Legal Processes

The Common Fund Program - Accelerating Translation of Glycoscience: Integration and Accessibility - aims to develop accessible and affordable new tools and technologies for studying carbohydrates that will allow biomedical researchers to significantly advance our understanding of the roles of these complex molecules in health and disease. This program will enable investigators who might not otherwise conduct research in the glycosciences, to undertake the study of carbohydrate structure and function. In support of these aims, this FOA seeks applications for a community-driven project to develop computational and informatics tools for the manipulation, analysis, interpretation, and integration of glycoscience data. The product of this research will be accessible resources for analysis of carbohydrate and glycoconjugate structural, analytical, and interaction data, and integration of that information within the context of comparable gene, protein, and lipid data and databases.