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This Funding Opportunity Announcement (FOA) solicits applications to start a new initiative, the Genomics of Gene Regulation (GGR), which is intended to explore genomic approaches to understanding the role of genomic sequence in the regulation of gene networks. A long-term goal of functional genomics is to decipher the rules by which gene networks are regulated and to understand how such regulation affects cellular function, development and disease. The GGR initiative will address the genome-proximal component of the regulation of gene networks by supporting a set of demonstration projects to develop and validate models that describe how a comprehensive set of sequence-based functional elements work in concert to regulate the finite set of genes that determine a biological phenomenon, using RNA amounts, and perhaps transcript structure, as the readout. This FOA seeks to support substantial improvement in the methods for developing gene regulatory network models, rather than an incremental improvement on existing methods. This work will move the field closer to the long-term goal of reading DNA sequence and accurately predicting when and at what levels a gene is expressed, in the context of a particular cell state. These demonstration projects will be organized as a research consortium to accelerate progress through the coordination of analytical methods and functional genomic data.

Genetic and genomic studies have identified genes and gene variants that may impact the fundamental biological mechanisms underpinning substance use disorders (SUDs).  Discovery of these genes/variants, while extremely valuable, is only the first step in understanding the molecular processes that influence SUDs. This Funding Opportunity Announcement (FOA) encourages basic functional genetic and genomic research in two areas:  1. functional validation to determine which candidate genes/variants/epigenetic/non-coding RNA features have an authentic role in SUDs, and 2. detailed elucidation of the molecular pathways and processes modulated by candidate genes/variants, particularly for those genes with an unanticipated role in SUDs.   

The Gilbert Family Foundation (GFF) is pleased to announce a Request for Proposals (RFP) for high-impact translational research in gene‐targeting strategies that address the underlying genetic abnormalities in neurofibromatosis type 1 (NF1) and have the potential to eradicate the disease. Proposals will be accepted for Team Science Awards defined as collaborative research amongst investigators with experience in gene‐targeting strategies in or outside the field of NF1. Through research that may be funded based on responses to this RFP, GFF plans to fund at least $7 million among multiple research institutions over three years. The objective of this RFP is to identify promising gene‐targeting strategies that address the underlying causes of NF1, have the potential to eradicate the disease, and prepare them for subsequent preclinical and clinical development. A responsive proposal must establish the feasibility of one of the following gene‐targeting approaches for NF1 and/or develop an enhanced or novel gene delivery system. Proposals that articulate a clear path to NF1 clinical application will be strongly favored

This FOA encourages applications for research projects that identify and/or validate chromosomal loci and variations in genes that are associated with vulnerability to addiction and that inform the likelihood of responsiveness to treatment. Applications that propose to examine intermediate phenotypes or endophenotypes to assess the molecular genetics of drug addiction, addiction vulnerability and/or their associated co-morbidities and how they are related to drug addiction are especially encouraged. Also encouraged are genetic as well as computational and large-scale genomic approaches, which may include but are not limited to linkage, linkage disequilibrium, case-control or family-based studies, and integration of data from other databases that may supplement substance abuse genetics and genomics data. Data may be collected from the general population, special populations, recent admixed populations, and/or animal models. Secondary data analysis of data collected from the general population, special populations, recent admixed populations, and/or animal models is also appropriate for this announcement. Investigators are encouraged to include, as a component of their project and as appropriate, gene x gene interactions, gene x environment interactions, gene x environment x development interactions, pharmacogenetics, and non-human models.

Genome-wide association studies (GWAS) identify statistical relationships between common single nucleotide variants (SNVs) across the genome and a trait of interest. Due to the correlated nature of nearby SNVs (i.e., linkage disequilibrium), GWAS implicate regions of the genome (loci) and do not necessarily pinpoint the causal variant(s), gene(s), isoform(s) or proximate molecular mechanism(s) underlying the trait association. Greater than 90% of genome-wide significant variants associated with traits fall within non-coding regions of the genome. A minority of these variants will be the actual causal variants and a majority will not affect the nearest genes. Moreover, functional annotation of the non-coding genome is still incomplete; the target genes of many genomic regulatory elements such as enhancers remain unknown. This presents a major challenge to mapping variants onto genes and genes onto traits. Thus, an immediate barrier to translating genetic associations into causal disease mechanisms is the uncertain relationship between statistically identified genetic variants and the resultant molecular changes influencing, directly or indirectly, a trait.

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. To meet the goal of catalyzing communities to enable direct tests of cause-and-effect hypotheses about genes and phenotypes in organisms for which such tools and infrastructure are presently lacking, EDGE proposals must include training and rapid dissemination plans enabling larger communities of investigators to utilize the newly-developed tools quickly, thereby catalyzing an increase in the capacity of research communities to test cause-and-effect hypotheses about genes and phenotypes in organisms for which such tools and infrastructure are presently lacking.

The goal of this FOA is to establish functional genotype-phenotype relationships of genes known to cause Alzheimer's disease (AD), genes or genetic variants suspected of altering the risk of AD, and genetic and biological modifiers that contribute to the disease process in neural cells using human pluripotent stem cells (hPSC) and genome editing approaches. Determining the function of AD candidate risk genes and genetic variants, identified in GWAS and other studies, in hPSC derived human neurons and glial cells is expected to identify new gene or cellular networks and molecular targets underlying the etiology of AD.

This Funding Opportunity Announcement (FOA) is intended to foster research towards a better understanding of the biological mechanisms of gene-environment interplay in human diseases and conditions. Through this FOA, the NIDCR, NIEHS, and NICHD solicit applications that use animal models, in vitro systems, or ex vivo approaches to conduct mechanistic investigation of the interplay of genes/gene networks and environmental factors in dental, oral, craniofacial (DOC), and other diseases and conditions.

The NIDDK Inflammatory Bowel Disease Genetics Consortium (IBDGC), in collaboration with the International IBD Genetics Consortium, has identified about 200 susceptibility loci for IBD. The IBDGC has recently been awarded renewed funding to identify causal genes and genetic variants within these loci, and to elucidate the mechanisms through which they contribute to the pathophysiology of IBD. However, the IBDGC's current resources permit them to explore the functions of only a limited set of genes within a limited set of physiological domains. The purpose of this Funding Opportunity Announcement (FOA) is to expand the number of genes and range of IBD-related phenotypes and physiological domains under study by means of collaborations of the IBDGC with investigators with expertise complementary to that of their own members. Proposed studies must not duplicate studies either ongoing or already completed by the IBDGC. Multi-site clinical trials will not be considered responsive to this FOA.

This Developmental Research Funding Opportunity intends to support gene function studies in collaboration with the Undiagnosed 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) is a limited competition FOA soliciting a cooperative agreement (U10) application from investigators currently supported under an existing study, entitled "Collaborative Study of the Genetics of Alcoholism (COGA)" to (i) identify genetic variants that affect the susceptibility to develop alcohol dependence in adult and adolescent populations, (ii) determine molecular and functional mechanisms of these variants, (iii) identify and characterize gene x gene and gene x environment interactions leading to alcoholism, (iv) develop and refine phenotypes that will facilitate genetic analysis,  (v) perform prospective studies of COGA probands.

This Funding Opportunity Announcement (FOA) issued by the National Institute on Alcoholism and Alcohol Abuse (NIAAA), solicits cooperative agreement (U10) applications focusing on studies that (i) identify genetic variants that affect the susceptibility to develop alcohol dependence in adult and adolescent populations, (ii) determine molecular and functional mechanisms of these variants, (iii) identify and characterize gene x gene and gene x environment interactions leading to alcoholism, (iv) develop and refine phenotypes that will facilitate genetic analysis. (v) perform prospective studies of COGA probands.

This program supports highly creative individuals in NHGRI priority research areas, such as the development of resources, approaches, or technologies that will accelerate genomic research on the structure of genomes, the biology of genomes, or the biology of disease; that will advance the science of genomic medicine; that will incorporate genomics to improve the effectiveness of healthcare; or that will advance genomic technology development, computational genomics, or research on the ethical, legal, and societal implications of genomics and genetics research.  This program supports the development of approaches that can be used broadly.  A hallmark of genomic research is comprehensiveness across the genome, such as all genes, variants, or regulatory elements, rather than specific sets.  The focus should be on developing approaches that can be applied generally, although an approach may be tested with specific genes, genomic elements, variants, cell types, diseases, traits, or model organisms.  Studies that focus on one or a few specific genes should be paradigm-setting and yield findings relevant at the genomic level.  The application should explain how broadly useful the approaches will be.

The Children's Tumor Foundation has issued a Request for Proposals for research related to gene-based therapeutic approaches for the treatment of neurofibromatosis type 1 (NF1). The initiative will support proof of principle in vitro studies focused on the feasibility of genome editing techniques (including but not limited to those based on CRISPR-Cas9) to correct pathogenic mutations in NF1 gene. Funding for each study will be $240,000 total (inclusive of 10 percent indirect costs) over two years.

: 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. EDGE proposals must include training and rapid dissemination plans enabling larger communities of investigators to utilize the newly-developed tools, thereby catalyzing an increase in the capacity of research communities to test cause-and-effect hypotheses about genes and phenotypes in organisms for which such tools and infrastructure are presently lacking.

This Funding Opportunity Announcement (FOA) is intended to foster research towards a better understanding of the biological mechanisms of gene-environment interplay in human diseases and conditions. Through this FOA, the NIDCR, NIEHS , and NICHD solicit applications to develop novel and robust experimental systems that offer approaches complementary to human epidemiologic or in vivo studies to facilitate mechanistic investigation of gene-environment interplay in dental, oral, craniofacial, and other diseases and conditions.

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. As of November 2019, the IMPC-KOMP2 KO mouse phenotyping effort has generated mutants in 9,051 mouse genes, completed phenotypes of 7153 lines, and released data for 6255 lines corresponding to 5861 mutant genes. Overall, the IMPC hopes to achieve broad-based phenotyping of roughly 20,000 KO strains. About 30% of these strains either are expected to be embryonic or perinatal lethal, or subviable. 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.

 The NIDDK Inflammatory Bowel Disease Genetics Consortium (IBDGC), in collaboration with the International IBD Genetics Consortium, has identified about 200 susceptibility loci for IBD.  The IBDGC has recently been awarded renewed funding to identify causal genes and genetic variants within these loci, and to elucidate the mechanisms through which they contribute to the pathophysiology of IBD.  However, the IBDGC's current resources permit them to explore the functions of only a limited set of genes within a limited set of physiological domains.  The purpose of this Funding Opportunity Announcement (FOA) is to expand the number of genes and range of IBD-related phenotypes and physiological domains under study by means of collaborations of the IBDGC with investigators with expertise complementary to that of their own members.  Proposed studies must not duplicate studies either ongoing or already completed by the IBDGC.  Multi-site clinical trials will not be considered responsive to this FOA.

The purpose of this FOA is to provide support for research projects that involve secondary data analyses of existing genome-wide data from genome-wide association studies or other large genomic datasets for the purpose of identifying gene-environment interactions. The ultimate objective of this funding opportunity is the discovery of complex interplays of genes and environmental factors in human populations which may disclose novel genetic susceptibilities to environmental exposures or a greater understanding of the role of environmental exposures in the development, progression, and severity of complex human diseases.

The purpose of this FOA is to provide support for research projects that involve secondary data analyses of existing genome-wide data from genome-wide association studies or other large genomic datasets for the purpose of identifying gene-environment interactions.  The ultimate objective of this funding opportunity is the discovery of complex interplays of genes and environmental factors in human populations which may disclose novel genetic susceptibilities to environmental exposures or a greater understanding of the role of environmental exposures in the development, progression, and severity of complex human diseases.