Grant List
Represents Grant table in the DB
GET /v1/grants?page%5Bnumber%5D=1392&sort=keywords
{ "links": { "first": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1&sort=keywords", "last": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1405&sort=keywords", "next": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1393&sort=keywords", "prev": "https://cic-apps.datascience.columbia.edu/v1/grants?page%5Bnumber%5D=1391&sort=keywords" }, "data": [ { "type": "Grant", "id": "5073", "attributes": { "award_id": "3U01AI141993-04S1", "title": "Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 18127, "first_name": "Conrad M.", "last_name": "Mallia", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-09-01", "end_date": "2022-12-31", "award_amount": 255683, "principal_investigator": { "id": 18128, "first_name": "Frances Eun-Hyung", "last_name": "Lee", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 265, "ror": "https://ror.org/03czfpz43", "name": "Emory University", "address": "", "city": "", "state": "GA", "zip": "", "country": "United States", "approved": true }, "abstract": "Human Vaccine Durability using Integrated Bioinformatics and a Novel in vitro Bone Marrow Mimic. Abstract: Long-lived plasma cells (LLPC) sustain protective antibody production for a lifetime and are the cellular basis of vaccine durability and require the bone marrow (BM) microniche to sustain survival. In our lab, we have definitively linked the long-lived viral serum antibodies to the BM cellular compartment within the healthy human BM (CD19-CD38hiCD138+) PC subset thereby establishing the LLPC compartment. We have also developed in vitro BM microniche cultures that mimic the BM microenvironment to sustain PC survival. In this application, we plan (1) to develop a novel in vitro biomarker of vaccine durability using this novel in vitro BM mimic and to dissect the mechanisms of early blood ASC of long-lived vaccines, acute viral infections, compared to short-lived vaccines, (2) to identify the unique identity of LLPC precursors in the blood early after vaccination, and (3) to study mechanisms of LLPC generation in disease models of Systemic Lupus Erythematosis which is characterized by high levels of long-lived antibodies and an abundance of LLPC. In summary, these studies will distinguish the cellular and molecular programs of LLPC generation and maintenance after immunization.", "keywords": [ "ATAC-seq", "Acute", "Affinity", "Antibodies", "Antibody Formation", "Antibody Repertoire", "Aspirate substance", "Autoantibodies", "Autoimmune Diseases", "B-Cell Antigen Receptor", "B-Lymphocytes", "Behavior", "Bioinformatics", "Biological Markers", "Blood", "Blood Circulation", "Bone Marrow", "CD19 gene", "Cell Compartmentation", "Cell Differentiation process", "Cell Maturation", "Cell Survival", "Cells", "Cellular Morphology", "Disease model", "Elderly", "Epigenetic Process", "Flow Cytometry", "Generations", "Genetic Transcription", "Hepatitis B", "Heterogeneity", "Homing", "Human", "Hypoxia", "Immune", "Immunization", "Immunoglobulin-Secreting Cells", "In Vitro", "Infection", "Interferon Type II", "Interleukin-6", "Kinetics", "Life", "Link", "Lupus", "Maintenance", "Measles", "Mediating", "Methods", "Molecular", "Mumps", "Pathway interactions", "Patients", "Peripheral", "Plasma Cells", "Population", "Production", "Property", "Reaction", "Rubella", "Serum", "Smallpox", "Streptococcus pneumoniae", "Structure of germinal center of lymph node", "Survivors", "Systemic Lupus Erythematosus", "T-Lymphocyte", "Tetanus", "Time", "Vaccination", "Vaccines", "Viral", "Virus Diseases", "Yellow Fever Vaccine", "cytokine", "epigenome", "human disease", "imprint", "influenza infection", "influenza virus vaccine", "insight", "lymph nodes", "mesenchymal stromal cell", "next generation sequencing", "novel", "novel marker", "pandemic influenza", "programs", "reconstruction", "response", "transcriptome", "transcriptome sequencing", "transcriptomics", "vaccine evaluation", "vaccine response" ], "approved": true } }, { "type": "Grant", "id": "8440", "attributes": { "award_id": "1F32HL156516-01", "title": "Defining the role of IRF5 in inflammatory hemophagocyte differentiation", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Heart Lung and Blood Institute (NHLBI)" ], "program_reference_codes": [], "program_officials": [ { "id": 24201, "first_name": "Allison", "last_name": "Gillaspy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-07-07", "end_date": "2022-07-06", "award_amount": 76053, "principal_investigator": { "id": 24202, "first_name": "Susan Priscilla", "last_name": "Canny", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 159, "ror": "https://ror.org/00cvxb145", "name": "University of Washington", "address": "", "city": "", "state": "WA", "zip": "", "country": "United States", "approved": true }, "abstract": "Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disorder associated with anemia, thrombocytopenia, and leukopenia and systemic hyperinflammation. Secondary HLH can be triggered by a range of diseases, including infections, cancer, or rheumatic disease. When triggered by rheumatic disease, it is often referred to as macrophage activation syndrome (MAS). HLH/MAS involves a hyperinflammatory response in which activated macrophages phagocytose red blood cells, white blood cells and platelets. Research in the Hamerman lab has revealed a critical role for cell-intrinsic Toll-like receptor (TLR) 7 signaling in the development of inflammatory hemophagocytes, a monocyte-derived macrophage that drives HLH/MAS in a mouse model. IRF5, which mediates TLR7 signaling in monocytes, contributes to differentiation of these hemophagocytes in the mouse although the signals driving differentiation of these cells in humans are unknown. This application aims to elucidate the role of IRF5 in the development of inflammatory hemophagocytes in both mice (Aim 1) and humans (Aim 2) and to further define the mechanism of cells of the monocyte lineage in cytokine storm syndromes. The proposed research will result in a better understanding of the role of myeloid cells in secondary HLH and may provide novel therapeutic targets or approaches. The fellowship training will take place at the Benaroya Research Institute, which focuses on understanding immune-mediated diseases, under the guidance of Dr. Jessica Hamerman and Dr. Jane Buckner. The training plan described in the supporting documents will provide essential steps toward preparing me for a career as an independent scientist. At the completion of my postdoctoral training, I will be able to transition to independence as a physician scientist.", "keywords": [ "ATAC-seq", "Address", "Anemia", "Aspirate substance", "Automobile Driving", "Blood Platelets", "Bone Marrow", "Bone Marrow Transplantation", "CD14 gene", "Cell Differentiation process", "Cells", "Complication", "DNA Sequence Alteration", "Data", "Development", "Disease", "Dose", "Erythrocytes", "FCGR3B gene", "Fellowship", "Functional disorder", "Gene Expression", "Genetic Transcription", "Haplotypes", "Heme", "Human", "Immune", "Individual", "Infection", "Inflammatory", "Interferon Type II", "Interferons", "Interleukin-1", "Interleukin-18", "Interleukin-6", "Kinetics", "Leukocytes", "Leukopenia", "Life", "Macrophage Colony-Stimulating Factor", "Macrophage activation syndrome", "Malignant Neoplasms", "Mediating", "Metabolic Diseases", "Modeling", "Mus", "Myelogenous", "Myeloid Cells", "Natural Killer Cells", "Organ", "Pathogenesis", "Pathogenicity", "Pathologic", "Pathway interactions", "Patients", "Pharmaceutical Preparations", "Physicians", "Receptor Signaling", "Refractory", "Research", "Research Institute", "Rheumatism", "Risk", "Role", "Scientist", "Secondary to", "Signal Transduction", "Signaling Molecule", "Splenic Red Pulp", "Steroids", "Stimulus", "Syndrome", "T-Lymphocyte", "TLR7 gene", "TLR8 gene", "Testing", "Therapeutic", "Thrombocytopenia", "Time", "Toll-like receptors", "Training", "Work", "bone cell", "career", "chemotherapy", "cytokine", "cytokine release syndrome", "cytopenia", "familial hemophagocytic lymphohistiocytosis", "in vivo", "inhibitor/antagonist", "macrophage", "monocyte", "mouse model", "new therapeutic target", "p65", "post-doctoral training", "response", "transcription factor" ], "approved": true } }, { "type": "Grant", "id": "5134", "attributes": { "award_id": "1R01AI162643-01A1", "title": "Molecular Basis of cDC1 Development", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 18278, "first_name": "Nancy", "last_name": "Vazquez-Maldonado", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2022-06-17", "end_date": "2027-05-31", "award_amount": 559854, "principal_investigator": { "id": 18279, "first_name": "Kenneth M", "last_name": "Murphy", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 827, "ror": "", "name": "WASHINGTON UNIVERSITY", "address": "", "city": "", "state": "MO", "zip": "", "country": "United States", "approved": true }, "abstract": "The initial adaptive immune response to tumors and many viruses relies on the priming of CD8 T cells to gen- erate cytolytic effector T cells that can specifically target tumors or virally infected cells. The priming of CD8 T cells to these agents is carried out in vivo by a particular type of antigen presenting cell that is a component of the myeloid system and a member of the family of dendritic cells. Classical dendritic cells (cDCs) comprise several closely related lineages that are clearly distinct from other myeloid cells such as macrophages, mono- cytes or granulocytes. Primarily, cDCs serve to activate T cells against infections in the central lymphoid tis- sues, rather than carrying out direct effector functions at sites of infections as the other myeloid lineages do. The cDCs are themselves comprised of at least two major branches, now called cDC1 and cDC2. The cDC1 is a lineage that specializes in the uptake and processing of cell-associated antigens, such as from tumors of virally infected cells and the expression of peptide epitopes on its cell surface in conjunction with MHC-I mole- cules. This form of antigen:MHC-I complex is able to activate CD8 T cells, and not CD4 T cells. This process is called cross-presentation. The cDC2 is not capable of carrying out cross-presentation to viruses or tumors in vivo. The cDC1 has many genetic and molecular differences from cDC2; cDC1 require a distinct set of tran- scription factors for their development that are not required for cDC2. This includes dependence on the tran- scription factors Nfil3, Id2, Irf8 and Batf3. Our recent work showed that the genetic hierarchy among these fac- tors has Nfil3 as the first and initiating factor, acting to indirectly induce Id2 and Batf3 via the suppression of the repressor Zeb2. However, it is still unknown how Nfil3 is induced to initiate this process, and how Nfil3 works to suppress Zeb2 expression. It has recently become important to understand these details because of the clini- cal interest to apply Flt3L administration as a therapeutic in expanding the in vivo population of cDC1. It has been known for some time that Fl3L can expand dendritic cells in general and expand cDC1 in particular. But we have uncovered a surprising and worrisome fact; Flt3L administration will expand cDC1-like cells even in Nfil3-deficient mice, which completely lack cDC1 beforehand. The expansion of cDC1 in Nfil3-deficent mice produced by Flt3L is of the same magnitude as the expansion in WT mice. Thus, Flt3L is inducing cDC1 by a different genetic route than normal cDC1 development. There has been no test of whether such cDC1 cells function normally and will boost an immune response. This application will systematically address this issue by Aim 1) defining the normal process by which Nfil3 is induced, Aim 2) define the mechanism by which NFIL3 drives cDC1 development, and Aim 3) determine whether Flt3-induced cDC1 function normally and determine the mechanism by which Flt3L bypasses the normal requirement for Nfil3 in cDC1 development.", "keywords": [ "ATAC-seq", "Address", "Antigen-Presenting Cells", "Antigens", "Binding", "Bypass", "CCAAT-Enhancer-Binding Proteins", "CD8-Positive T-Lymphocytes", "CRISPR/Cas technology", "Cell physiology", "Cell surface", "Cells", "ChIP-seq", "Chimeric Proteins", "Clinical", "Complex", "Critiques", "Cross Presentation", "Data", "Dendritic Cells", "Dependence", "Development", "Elements", "Enhancers", "Epitopes", "Exhibits", "FLT3 gene", "FLT3 ligand", "Family member", "Gene Targeting", "Generations", "Genes", "Genetic", "Genetic Transcription", "Goals", "Homeostasis", "Human", "Immune response", "Immunity", "In Vitro", "Infection", "Literature", "Lymphoid Tissue", "MHC antigen", "Methods", "Mole the mammal", "Molecular", "Molecular Genetics", "Mus", "Myelogenous", "Myeloid Cells", "Output", "Pathway interactions", "Peptides", "Population", "Process", "Production", "Proteins", "Publishing", "Reagent", "Reporter", "Reporting", "Role", "Route", "Signal Transduction", "Site", "Specific qualifier value", "Suggestion", "System", "T cell response", "T-Lymphocyte", "Testing", "Therapeutic", "Time", "Tumor-Derived", "Vaccines", "Viral", "Virus", "Work", "adaptive immune response", "design", "effector T cell", "granulocyte", "in vivo", "interest", "macrophage", "novel", "progenitor", "response", "stem cells", "tool", "transcription factor", "tumor", "uptake" ], "approved": true } }, { "type": "Grant", "id": "5209", "attributes": { "award_id": "3R01AI048638-22S1", "title": "Metabolic imprinting of dendritic cell fate and function in tissues", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 18435, "first_name": "Wendy F.", "last_name": "Davidson", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2001-03-01", "end_date": "2025-01-31", "award_amount": 118275, "principal_investigator": { "id": 18436, "first_name": "BALI", "last_name": "PULENDRAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [], "awardee_organization": { "id": 266, "ror": "https://ror.org/00f54p054", "name": "Stanford University", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Dendritic cells (DCs) play a central role in sensing pathogens and tuning immune responses. Functionally distinct subsets of DCs can stimulate different types of immune responses, but DCs also display functional plasticity in response to microbial stimuli or signals from the tissue microenvironment. However, it is now clear that DCs sense not just microbial stimuli, but also various stress signals (e.g. amino acid starvation), through ancient stress sensing mechanisms, leading to a metabolic reprogramming of their function. In particular our recent work has revealed fundamental roles for two major amino acid sensors GCN2 and mTOR, in programming DCs to modulate adaptive immunity and inflammation. We have shown that GCN2 plays a role in programming DCs to respond to viral vaccination, and in controlling intestinal inflammation by promoting autophagy and suppressing inflammasome activation in gut APCs and epithelial cells. Furthermore, our recent data demonstrates that GCN2 regulates allergic inflammation in the lung. In addition to these effects of GCN2, we have recently shown that mTOR regulates developmental fate of DCs and alveolar macrophages (AMs) in the lung, and reprograms their metabolic state to modulate the outcome of allergic inflammation. In the following aims, we will determine the mechanisms of this metabolic imprinting. Aim 1: To determine the mechanisms by which mTOR controls the homeostasis and function of lung DCs and AMs in the steady state and during allergic inflammation. Our recent work demonstrates that in mice in which mTOR is genetically ablated in CD11c+ cells (mTORAPC mice): (i) CD103+ DCs and AMs in the lung are greatly reduced in number, in the steady state. (ii) Although the lung CD11c+CD11b+ DCs were numerically unaffected, they were skewed in their transcriptional identity towards the macrophage/monocytic profile. (iii) Lung allergic Th2 inflammation was skewed toward the Th17/neutrophilic phenotype. In the present aim, we will investigate the mechanisms underlying these effects, and investigate the potential role of 4E-BP3 dependent translational control, lipid metabolism and epigenetic reprograming in mediating the effects of mTOR signaling. Aim 2: To determine the mechanisms by which GCN2 regulates Th2 responses and allergic inflammation. Our preliminary data demonstrate that GCN2 knockout mice display markedly reduced allergic inflammation in the lung. In this aim we will determine the molecular mechanisms underlying this effect. The successful completion of these aims will yield rich mechanistic insights about metabolic imprinting of DC fate and function.", "keywords": [ "ATAC-seq", "Adoptive Transfer", "Allergic", "Allergic inflammation", "Alveolar Macrophages", "Amino Acids", "Autophagocytosis", "Bone Marrow", "Cell physiology", "Cells", "Cellular biology", "Chimera organism", "Data", "Dendritic Cells", "Development", "EIF4EBP1 gene", "Epigenetic Process", "Epithelial Cells", "FRAP1 gene", "Genetic Transcription", "Genetic Translation", "Hematopoietic", "Homeostasis", "ITGAM gene", "ITGAX gene", "Immune response", "Immunity", "In Situ", "Infection", "Inflammasome", "Inflammation", "Knockout Mice", "Lung", "Lymphoid Cell", "Mediating", "Metabolic", "Modeling", "Molecular", "Mus", "Natural Killer Cells", "Nature", "Organ", "Outcome", "Pathway interactions", "Phenotype", "Play", "Raptors", "Role", "Signal Pathway", "Signal Transduction", "Spleen", "Starvation", "Stimulus", "Stress", "Tissues", "Vaccination", "Viral", "Work", "adaptive immunity", "cell type", "conditional knockout", "functional plasticity", "gene repression", "imprint", "inflammatory disease of the intestine", "insight", "lipid metabolism", "mTOR Signaling Pathway", "macrophage", "metabolic profile", "microbial", "monocyte", "neutrophil", "pathogen", "programs", "pulmonary function", "receptor", "response", "sensor", "transcription factor" ], "approved": true } }, { "type": "Grant", "id": "7385", "attributes": { "award_id": "3U01AI131386-03S1", "title": "High Precision System Analysis of Infant Immune Responses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6621, "first_name": "Mercy R.", "last_name": "Prabhudas", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-18", "end_date": "2022-07-31", "award_amount": 360758, "principal_investigator": { "id": 21219, "first_name": "Jacques F", "last_name": "Banchereau", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 873, "ror": "https://ror.org/021sy4w91", "name": "Jackson Laboratory", "address": "", "city": "", "state": "ME", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7275, "first_name": "Octavio", "last_name": "Ramilo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 879, "ror": "", "name": "RESEARCH INST NATIONWIDE CHILDREN'S HOSP", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 879, "ror": "", "name": "RESEARCH INST NATIONWIDE CHILDREN'S HOSP", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "The COVID-19 pandemic is a worldwide emergency causing major social and economic disruptions. As an emergent viral infection, there are major knowledge gaps regarding COVID-19. In particular, there is limited information thus far on the impact of COVID-19 on pregnant women and their infants. Initial studies suggest that clinical manifestations during pregnancy are similar to those identified in non-pregnant adults, and recent reports have described cases of severe pneumonia and ARDS in pregnant women. Information on the impact of maternal infection on the infant is also limited. Investigators in China documented perinatal transmission in a small number of newborn infants. A common feature of severe COVID-19 appears to be inflammation, which is a known risk factor for poor pregnancy outcomes and can impact the development of the infant immune system. Thus, there is an urgent need to understand the role of COVID-19 during pregnancy and its impact on the infant. Our Parent U01 is focused on high-resolution analysis of immune responses in healthy infants. The goal of this supplement is to determine how maternal COVID-19 infection affects the infant immune system, which we will achieve by analyzing the interplay between the maternal and infant immune systems in the context of COVID- 19. We hypothesize that COVID-19 during pregnancy leaves a stable imprint on the infant immune system defined by enhanced inflammation and dysregulated responses to vaccines. Although our focus is the analysis of infant immune responses, a comprehensive system analysis approach is required to efficiently identify the most relevant immunologic and virologic factors that determine COVID-19 outcomes in pregnant women, and how they impact the immune responses of the fetus and the infant. We propose conducting a prospective longitudinal study in pregnant women with COVID-19 occurring at any time during pregnancy and follow their infants longitudinally to assess their immune responses until 7 months of age. As a reference control, we will include a cohort of non-COVID-19 pregnant women and their infants.", "keywords": [ "ATAC-seq", "Adult", "Adult Respiratory Distress Syndrome", "Affect", "Age-Months", "Aliquot", "Amniotic Fluid", "Antibody Response", "Antibody titer measurement", "Biological Assay", "Blood", "COVID-19", "COVID-19 pandemic", "Cells", "Characteristics", "China", "Clinical", "Clinical Virology", "Detection", "Development", "Discipline of obstetrics", "Disease", "Economics", "Emergency Situation", "Enzyme-Linked Immunosorbent Assay", "Epidemiology", "Evaluation", "Evolution", "Fetus", "Fever", "First Pregnancy Trimester", "Flow Cytometry", "Future", "Genes", "Goals", "Human", "Immune", "Immune response", "Immune system", "Immunization", "Immunologic Factors", "Immunologics", "Immunology procedure", "Immunophenotyping", "Infant", "Infant Development", "Infection", "Inflammation", "Knowledge", "Longitudinal observational study", "Longitudinal prospective study", "Lower Respiratory Tract Infection", "Maternal-fetal medicine", "Measures", "Molecular Immunology", "Molecular Virology", "Mothers", "Neonatology", "Newborn Infant", "Nose", "Outcome", "Parents", "Perinatal transmission", "Peripheral Blood Mononuclear Cell", "Pneumonia", "Pregnancy", "Pregnancy Outcome", "Pregnant Women", "Reporting", "Research", "Research Personnel", "Resolution", "Risk Factors", "Role", "Sampling", "Second Pregnancy Trimester", "Serum", "Severities", "Subgroup", "Swab", "Symptoms", "Systems Analysis", "Third Pregnancy Trimester", "Time", "Umbilical Cord Blood", "Upper respiratory tract", "Vaccination", "Vaccines", "Vagina", "Viral", "Viral Load result", "Virus", "Virus Diseases", "Whole Blood", "acute infection", "base", "bronchial epithelium", "cohort", "design", "experience", "imprint", "multidisciplinary", "novel", "parent grant", "rectal", "respiratory virus", "response", "single-cell RNA sequencing", "social", "transcriptome", "transcriptome sequencing", "transmission process", "virology" ], "approved": true } }, { "type": "Grant", "id": "6037", "attributes": { "award_id": "3U01AI131386-05S1", "title": "High Precision System Analysis of Infant Immune Responses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 20600, "first_name": "Mercy R.", "last_name": "Prabhudas", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-18", "end_date": "2023-07-31", "award_amount": 1258393, "principal_investigator": { "id": 20601, "first_name": "Octavio", "last_name": "Ramilo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] }, "other_investigators": [ { "id": 20602, "first_name": "Duygu", "last_name": "Ucar", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 879, "ror": "", "name": "RESEARCH INST NATIONWIDE CHILDREN'S HOSP", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "This project seeks to surmount current limitations in our understanding of early infant immunity through longitudinal genomic and cellular studies of immune development and primary responses to routine two-month vaccines. Infants and young children are more susceptible to invasive infections than adults owing to overall reduced competency of protective immune responses, including to vaccines, which require administration of multiple doses over several months for adequate long-term protection. While immunization programs have dramatically decreased the global morbidity and mortality caused by infections, it remains that infectious diseases are the most frequent cause of death in infants and young children. The cellular, molecular and genomic mechanisms that contribute to this vulnerability are largely unknown. Ever more powerful tools in genomics and systems biology offer exciting opportunities to resolve these knowledge gaps through detailed analysis of the transcriptomic, epigenomic and functional signatures of infant immune cell populations. However, such studies have been limited by the difficulty in accessing clinical samples from infants, the incompatibility of many genomic technologies for use in small-volume samples, and the lack of bioinformatic tools for integrating and interpreting complimentary yet complex datasets. This proposal will capitalize on our experience studying the infant immune response, our access to infant populations, and our expertise in developing immunogenomic assays for use in human blood-derived immune cells (PBMCs). Specifically, we propose a longitudinal analysis of PBMCs from infants i) at 2, 6 and 12 months, to establish the baseline cellular, phenotypic and genomic signatures of immune development (Aim 1), and ii) at key time points over the course of routine two-month vaccinations, to identify the cellular, phenotypic and genomic signatures associated with primary immune responses to vaccines (Aim 2). We will use an innovative immunogenomic Profiling and Analysis Pipeline (iPAP) we developed that allows us to extract maximal transcriptomic (RNA-seq), epigenomic (ATAC-seq), isoformic (SMRT-seq), cytometric (50-parameter flow cytometry) and immunophenotypic (CyTOF) information from a single infant blood sample, and to integrate these distinct datasets for unparalleled depth of insight into the correlated cellular and genomic signatures of immune development and vaccine responsiveness. Our approach is unbiased, multifaceted and highly technology-driven, combining many of the most cutting-edge genomic and quantitative cell-based technologies with our deep experience in applying these technologies for use in human infant immune cells. In line with the goals of this RFA, this project will yield a comprehensive dataset from infants that can be used to identify fundamental mechanisms and pathways associated with immune development and primary responses to vaccines, and will set the stage for future studies aimed at designing new interventions that induce more potent and protective immune responses for young infants.", "keywords": [ "ATAC-seq", "Adult", "Affect", "Age-Months", "Antibody Response", "Antigens", "Bacterial Infections", "Biological Assay", "Blood", "Blood Volume", "Blood specimen", "Cause of Death", "Cells", "Characteristics", "Child", "Chromatin", "Clinical", "Code", "Communicable Diseases", "Competence", "Complex", "Custom", "Cytometry", "Data", "Data Set", "Development", "Disease", "Dose", "Flow Cytometry", "Foundations", "Future", "Gene Expression", "Gene Expression Profile", "Gene Expression Profiling", "Genes", "Genetic Transcription", "Genomics", "Goals", "Human", "Hybrids", "Immune", "Immune response", "Immune system", "Immunity", "Immunization Programs", "Immunogenomics", "Immunophenotyping", "Infant", "Infant Health", "Infection", "Intervention", "Knowledge", "Life", "Maps", "Molecular", "Molecular Profiling", "Morbidity - disease rate", "Pathway interactions", "Peripheral Blood Mononuclear Cell", "Phenotype", "Population", "Protein Isoforms", "Regulation", "Resolution", "Sample Size", "Sampling", "Shapes", "Systems Analysis", "Systems Biology", "Technology", "Time", "Transcript", "Untranslated RNA", "Vaccination", "Vaccines", "Work", "age related", "analysis pipeline", "analytical tool", "base", "bioinformatics tool", "cell type", "cohort", "design", "epigenome", "epigenomics", "experience", "flexibility", "genomic signature", "high risk", "immune function", "imprint", "innovation", "innovative technologies", "insight", "longitudinal analysis", "mortality", "neutralizing antibody", "response", "single molecule real time sequencing", "tool", "transcriptome", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "7384", "attributes": { "award_id": "3U01AI131386-04S1", "title": "High Precision System Analysis of Infant Immune Responses", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 6621, "first_name": "Mercy R.", "last_name": "Prabhudas", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-06-18", "end_date": "2022-07-31", "award_amount": 1668904, "principal_investigator": { "id": 21219, "first_name": "Jacques F", "last_name": "Banchereau", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 873, "ror": "https://ror.org/021sy4w91", "name": "Jackson Laboratory", "address": "", "city": "", "state": "ME", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 7275, "first_name": "Octavio", "last_name": "Ramilo", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 879, "ror": "", "name": "RESEARCH INST NATIONWIDE CHILDREN'S HOSP", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true } ] } ], "awardee_organization": { "id": 879, "ror": "", "name": "RESEARCH INST NATIONWIDE CHILDREN'S HOSP", "address": "", "city": "", "state": "OH", "zip": "", "country": "United States", "approved": true }, "abstract": "This project seeks to surmount current limitations in our understanding of early infant immunity through longitudinal genomic and cellular studies of immune development and primary responses to routine two-month vaccines. Infants and young children are more susceptible to invasive infections than adults owing to overall reduced competency of protective immune responses, including to vaccines, which require administration of multiple doses over several months for adequate long-term protection. While immunization programs have dramatically decreased the global morbidity and mortality caused by infections, it remains that infectious diseases are the most frequent cause of death in infants and young children. The cellular, molecular and genomic mechanisms that contribute to this vulnerability are largely unknown. Ever more powerful tools in genomics and systems biology offer exciting opportunities to resolve these knowledge gaps through detailed analysis of the transcriptomic, epigenomic and functional signatures of infant immune cell populations. However, such studies have been limited by the difficulty in accessing clinical samples from infants, the incompatibility of many genomic technologies for use in small-volume samples, and the lack of bioinformatic tools for integrating and interpreting complimentary yet complex datasets. This proposal will capitalize on our experience studying the infant immune response, our access to infant populations, and our expertise in developing immunogenomic assays for use in human blood-derived immune cells (PBMCs). Specifically, we propose a longitudinal analysis of PBMCs from infants i) at 2, 6 and 12 months, to establish the baseline cellular, phenotypic and genomic signatures of immune development (Aim 1), and ii) at key time points over the course of routine two-month vaccinations, to identify the cellular, phenotypic and genomic signatures associated with primary immune responses to vaccines (Aim 2). We will use an innovative immunogenomic Profiling and Analysis Pipeline (iPAP) we developed that allows us to extract maximal transcriptomic (RNA-seq), epigenomic (ATAC-seq), isoformic (SMRT-seq), cytometric (50-parameter flow cytometry) and immunophenotypic (CyTOF) information from a single infant blood sample, and to integrate these distinct datasets for unparalleled depth of insight into the correlated cellular and genomic signatures of immune development and vaccine responsiveness. Our approach is unbiased, multifaceted and highly technology-driven, combining many of the most cutting-edge genomic and quantitative cell-based technologies with our deep experience in applying these technologies for use in human infant immune cells. In line with the goals of this RFA, this project will yield a comprehensive dataset from infants that can be used to identify fundamental mechanisms and pathways associated with immune development and primary responses to vaccines, and will set the stage for future studies aimed at designing new interventions that induce more potent and protective immune responses for young infants.", "keywords": [ "ATAC-seq", "Adult", "Affect", "Age-Months", "Antibody Response", "Antigens", "Bacterial Infections", "Biological Assay", "Blood", "Blood Volume", "Blood specimen", "Cause of Death", "Cells", "Characteristics", "Child", "Chromatin", "Clinical", "Code", "Communicable Diseases", "Competence", "Complex", "Custom", "Cytometry", "Data", "Data Set", "Development", "Disease", "Dose", "Flow Cytometry", "Foundations", "Future", "Gene Expression", "Gene Expression Profiling", "Genes", "Genetic Transcription", "Genomics", "Goals", "Human", "Hybrids", "Immune", "Immune response", "Immune system", "Immunity", "Immunization Programs", "Immunogenomics", "Immunophenotyping", "Infant", "Infant Health", "Infection", "Intervention", "Knowledge", "Life", "Maps", "Molecular", "Molecular Profiling", "Morbidity - disease rate", "Pathway interactions", "Peripheral Blood Mononuclear Cell", "Phenotype", "Population", "Protein Isoforms", "Regulation", "Resolution", "Sample Size", "Sampling", "Shapes", "Systems Analysis", "Systems Biology", "Technology", "Time", "Transcript", "Untranslated RNA", "Vaccination", "Vaccines", "Work", "age related", "analysis pipeline", "analytical tool", "base", "bioinformatics tool", "cell type", "cohort", "design", "epigenome", "epigenomics", "experience", "flexibility", "genomic signature", "high risk", "immune function", "imprint", "innovation", "innovative technologies", "insight", "longitudinal analysis", "mortality", "neutralizing antibody", "response", "single molecule real time sequencing", "tool", "transcriptome", "transcriptome sequencing", "transcriptomics" ], "approved": true } }, { "type": "Grant", "id": "9268", "attributes": { "award_id": "1R01AI157513-01", "title": "Genetic architecture of host response to tickborne disease in Peromyscus leucopus", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 25007, "first_name": "Nadine", "last_name": "Bowden", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-09-17", "end_date": "2025-08-31", "award_amount": 724038, "principal_investigator": { "id": 25008, "first_name": "Alan G.", "last_name": "Barbour", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 971, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 25009, "first_name": "ANTHONY Douglas", "last_name": "LONG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 971, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Lyme disease, one of the most commonly reported infectious diseases in North America, is caused by the tick-borne bacterium Borreliella burgdorferi. Although humans and other large mammals can be infected by B. burgdorferi, in order to complete its life-cycle in the wild the bacteria relies on rodent reservoirs, the major one being Peromyscus leucopus, the white-footed deermouse. The role of P. leucopus in Lyme disease and several other tick-borne diseases is analogous to that of bats as reservoirs for SARS coronaviruses and Ebola virus. In this proposal we continue the development of P. leucopus as an emerging genetic model system for the study of infectious and other diseases by maintaining and expanding genomic and biological resources for this species. These resources are the starting point for any gene-focused experiments in the Peromyscus genus. The primary goal of this proposal is to identify segregating genetic factors that impact the competence of P. leucopus as a reservoir of B. burgdorferi. The trait of reservoir competence is measured as the prevalence of infection and corresponding bacterial burdens among a cohort of nymphs that had molted from larvae previously fed on experimentally-infected deermice. Secondary endpoints include rates of growth and decline of the bacteria in the blood and skin of the animals and selected host responses, such as antibodies to the agent and inflammation of tissues, over the time course of the infection. It would normally be extremely difficult to carry-out large-scale genotyping and/or genetic crosses in an emerging rodent model. Here we show that our genome assembly for P. leucopus in concert with low pass short read sequences from a long-term closed colony of deermice can be leveraged to accurately impute SNP and haplotype genotypes on a genome- wide scale. These genotypes are then used to identify genes contributing to the remarkable capacity of P. leucopus to serve as a key reservoir host for B. burgdorferi and other disease agents. Finally, a subset of identified genes will be validated via CRISPR/Cas9 gene knock-outs in P. leucopus spearheaded by the person who pioneered transgenics for this genus. The identification of reservoir competence mediating genes may suggest better interventions to block transmission and provide insights into the management of human infections.", "keywords": [ "ATAC-seq", "Adult", "Animals", "Antibodies", "Bacteria", "Biological", "Biological Models", "Blood", "Borrelia burgdorferi", "Breeding", "CRISPR gene drive", "CRISPR/Cas technology", "Candidate Disease Gene", "Chiroptera", "Chromatin", "Chromosome Mapping", "Chromosomes", "Communities", "Competence", "Coupled", "Data", "Deer Mouse", "Development", "Diploidy", "Disease", "Disease Notification", "Ebola virus", "Enhancers", "Equilibrium", "Euthanasia", "Female", "Gene Targeting", "Genes", "Genetic", "Genetic Crosses", "Genetic Models", "Genetic Structures", "Genome", "Genomic Segment", "Genomics", "Genotype", "Goals", "Growth", "Haplotypes", "High Prevalence", "Human", "Immune response", "Immunity", "Infection", "Inflammation", "Intervention", "Knock-out", "Larva", "Life Cycle Stages", "Linkage Disequilibrium", "Lyme Disease", "Mammals", "Measurement", "Measures", "Mediating", "Modeling", "Molting", "Muridae", "Mus", "North America", "Nymph", "Organ", "Parasites", "Pathology", "Peromyscus", "Persons", "Phenotype", "Population", "Prevalence", "Process", "Resources", "Rodent", "Rodent Model", "Role", "SARS coronavirus", "Sample Size", "Skin", "Tick-Borne Diseases", "Ticks", "Time", "Tissues", "Transgenic Model", "Transgenic Organisms", "United States", "Variant", "Vector-transmitted infectious disease", "Wild Animals", "animal colony", "base", "chronic infection", "cohort", "combat", "experimental study", "foot", "forward genetics", "genetic approach", "genetic architecture", "genome browser", "genome wide association study", "genome-wide", "insight", "inter-individual variation", "interest", "knockout gene", "male", "microbial", "pathogen", "primary endpoint", "promoter", "rate of change", "secondary endpoint", "success", "tick-borne", "trait", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "9269", "attributes": { "award_id": "5R01AI157513-02", "title": "Genetic architecture of host response to tickborne disease in Peromyscus leucopus", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Institute of Allergy and Infectious Diseases (NIAID)" ], "program_reference_codes": [], "program_officials": [ { "id": 25007, "first_name": "Nadine", "last_name": "Bowden", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2020-09-17", "end_date": "2025-08-31", "award_amount": 691155, "principal_investigator": { "id": 25008, "first_name": "Alan G.", "last_name": "Barbour", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 971, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [ { "id": 25009, "first_name": "ANTHONY Douglas", "last_name": "LONG", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "awardee_organization": { "id": 971, "ror": "", "name": "UNIVERSITY OF CALIFORNIA-IRVINE", "address": "", "city": "", "state": "CA", "zip": "", "country": "United States", "approved": true }, "abstract": "Lyme disease, one of the most commonly reported infectious diseases in North America, is caused by the tick-borne bacterium Borreliella burgdorferi. Although humans and other large mammals can be infected by B. burgdorferi, in order to complete its life-cycle in the wild the bacteria relies on rodent reservoirs, the major one being Peromyscus leucopus, the white-footed deermouse. The role of P. leucopus in Lyme disease and several other tick-borne diseases is analogous to that of bats as reservoirs for SARS coronaviruses and Ebola virus. In this proposal we continue the development of P. leucopus as an emerging genetic model system for the study of infectious and other diseases by maintaining and expanding genomic and biological resources for this species. These resources are the starting point for any gene-focused experiments in the Peromyscus genus. The primary goal of this proposal is to identify segregating genetic factors that impact the competence of P. leucopus as a reservoir of B. burgdorferi. The trait of reservoir competence is measured as the prevalence of infection and corresponding bacterial burdens among a cohort of nymphs that had molted from larvae previously fed on experimentally-infected deermice. Secondary endpoints include rates of growth and decline of the bacteria in the blood and skin of the animals and selected host responses, such as antibodies to the agent and inflammation of tissues, over the time course of the infection. It would normally be extremely difficult to carry-out large-scale genotyping and/or genetic crosses in an emerging rodent model. Here we show that our genome assembly for P. leucopus in concert with low pass short read sequences from a long-term closed colony of deermice can be leveraged to accurately impute SNP and haplotype genotypes on a genome- wide scale. These genotypes are then used to identify genes contributing to the remarkable capacity of P. leucopus to serve as a key reservoir host for B. burgdorferi and other disease agents. Finally, a subset of identified genes will be validated via CRISPR/Cas9 gene knock-outs in P. leucopus spearheaded by the person who pioneered transgenics for this genus. The identification of reservoir competence mediating genes may suggest better interventions to block transmission and provide insights into the management of human infections.", "keywords": [ "ATAC-seq", "Adult", "Animals", "Antibodies", "Bacteria", "Biological", "Biological Models", "Blood", "Borrelia burgdorferi", "Breeding", "CRISPR gene drive", "CRISPR/Cas technology", "Candidate Disease Gene", "Chiroptera", "Chromatin", "Chromosome Mapping", "Chromosomes", "Communities", "Competence", "Coupled", "Data", "Deer Mouse", "Development", "Diploidy", "Disease", "Disease Notification", "Ebola virus", "Enhancers", "Equilibrium", "Euthanasia", "Female", "Gene Targeting", "Genes", "Genetic", "Genetic Crosses", "Genetic Models", "Genetic Structures", "Genome", "Genomic Segment", "Genomics", "Genotype", "Goals", "Growth", "Haplotypes", "High Prevalence", "Human", "Immune response", "Immunity", "Infection", "Inflammation", "Intervention", "Knock-out", "Larva", "Life Cycle Stages", "Linkage Disequilibrium", "Lyme Disease", "Mammals", "Measurement", "Measures", "Mediating", "Modeling", "Molting", "Muridae", "Mus", "North America", "Nymph", "Organ", "Parasites", "Pathology", "Peromyscus", "Persons", "Phenotype", "Population", "Prevalence", "Process", "Resources", "Rodent", "Rodent Model", "Role", "SARS coronavirus", "Sample Size", "Skin", "Tick-Borne Diseases", "Ticks", "Time", "Tissues", "Transgenic Model", "Transgenic Organisms", "United States", "Variant", "Vector-transmitted infectious disease", "Wild Animals", "animal colony", "base", "chronic infection", "cohort", "combat", "experimental study", "foot", "forward genetics", "genetic approach", "genetic architecture", "genome browser", "genome wide association study", "genome-wide", "insight", "inter-individual variation", "interest", "knockout gene", "male", "microbial", "pathogen", "primary endpoint", "promoter", "rate of change", "secondary endpoint", "success", "tick transmission", "tick-borne", "trait", "transmission process" ], "approved": true } }, { "type": "Grant", "id": "8081", "attributes": { "award_id": "3UM1HG009382-04S1", "title": "Mapping of Novel Candidate Functional Elements with Bru-Seq Technology", "funder": { "id": 4, "ror": "https://ror.org/01cwqze88", "name": "National Institutes of Health", "approved": true }, "funder_divisions": [ "National Human Genome Research Institute (NHGRI)" ], "program_reference_codes": [], "program_officials": [ { "id": 23002, "first_name": "Daniel A", "last_name": "Gilchrist", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [] } ], "start_date": "2021-02-01", "end_date": "2022-01-31", "award_amount": 460492, "principal_investigator": { "id": 23972, "first_name": "MATS", "last_name": "LJUNGMAN", "orcid": null, "emails": "", "private_emails": "", "keywords": null, "approved": true, "websites": null, "desired_collaboration": null, "comments": null, "affiliations": [ { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true } ] }, "other_investigators": [], "awardee_organization": { "id": 770, "ror": "", "name": "UNIVERSITY OF MICHIGAN AT ANN ARBOR", "address": "", "city": "", "state": "MI", "zip": "", "country": "United States", "approved": true }, "abstract": "The ENCODE project has provided a tremendous resource for scientists with a treasure trove of data from a large set of different cell types describing RNA expression (RNA-seq), epigenetic signatures (ChIP-seq), chromatin structure (DNase-seq, ATAC-seq, Hi-C, ChIA-PET) and binding patterns of specific proteins to both DNA and RNA (ChIP-seq, CLIP-seq, RIP-seq). While RNA- seq data is very informative in providing signatures of steady-state levels of RNA expressed for particular genes, individual contributions of RNA synthesis and degradation to the steady-state- level of RNA cannot be determined. Furthermore, these expression data sets are static and do not provide dynamic information on specific cell responses. Regarding the ChIP-seq analyses of specific histone modifications, such as high H3K1me1 and H3K27ac and low H3K4me3, they are valuable for the identification of putative enhancer elements in a particular cell type but does not inform on whether such functional elements are functionally active. We have recently developed a set of techniques that are based on the specific labeling of nascent RNA with bromouridine (Bru) followed by lysis, capturing of the Bru-labeled RNA using specific antibodies and deep sequencing. Bru-seq captures the “nascent RNA transcriptome”, a signature of ongoing transcription in the genome where the relative rates of transcription of all genes can be obtained. In BruChase-seq, cells are labeled with Bru and then chased in uridine for different periods of time to allow for the determination of the “RNA stabilome” where the relative RNA degradation rates genome-wide are assessed. Finally, BruUV-seq allows for the capturing of RNA species that normally are rapidly turned over by the RNA exosome and allows for a different view of the nascent transcriptome where active enhancer elements and other candidate functional elements generating unstable RNAs are identified genome-wide. In this UM1 granting period we have used our Bru-seq suite of assays on human cell lines to complement existing data that have previously been generated using various genomic assays. In year 5 of this granting period, we are planning to extend the Bru-seq analysis for 1) COVID-19 cell line experiments, 2) immune/blood cell samples and 3) genetic perturbations.", "keywords": [ "ATAC-seq", "Antibodies", "Binding", "Biological Assay", "Blood Cells", "Bromouridine", "COVID-19", "Cell Line", "Cells", "ChIP-seq", "Chromatin Interaction Analysis by Paired-End Tag Sequencing", "Chromatin Structure", "Complement", "Cytolysis", "DNA", "DNase I hypersensitive sites sequencing", "Data", "Data Set", "Elements", "Enhancers", "Epigenetic Process", "Genes", "Genetic", "Genetic Enhancer Element", "Genetic Transcription", "Genome", "Genomics", "Goals", "Grant", "Hi-C", "Human", "Human Cell Line", "Human Genome", "Immune", "Individual", "Label", "Pattern", "Proteins", "RNA", "RNA Degradation", "RNA Splicing", "RNA chemical synthesis", "RNA immunoprecipitation sequencing", "Regulation", "Regulatory Element", "Resources", "Sampling", "Scientist", "Techniques", "Technology", "Time", "Transcript", "Translations", "Uridine", "base", "cell type", "crosslinking and immunoprecipitation sequencing", "deep sequencing", "exosome", "experimental study", "genome-wide", "histone modification", "novel", "promoter", "response", "transcriptome" ], "approved": true } } ], "meta": { "pagination": { "page": 1392, "pages": 1405, "count": 14046 } } }