Document text
Principal Investigator: GREGORY C GIBSON
Organization: GEORGIA INSTITUTE OF TECHNOLOGY
Fiscal Year: 2019
Award: $175,023
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Project Summary
Over the past decade, the NIDDK IBDGC (Inflammatory Bowel Disease Genetics Consortium) has
generated extraordinary datasets in support of genetic analysis of the onset, progression, and therapeutic
response to Crohn's disease and ulcerative colitis. This Ancillary project will complement ongoing IBDGC
research by providing parallel statistical genetic analyses focused on transcriptomics, while also developing
a novel strategy for genetic manipulation of patient-derived epithelial cells. There are four major
biomedical genomics focus areas addressed by the research, namely fine mapping of loci influencing
inflammatory bowel disease, elucidation of the cell and molecular function of causal genes, understanding
how polymorphism influences pathology, and translating quantitative genetic discoveries into clinical
outcomes. Specifically, integrative genomics expertise will be used to refine the credible intervals
responsible for complex association signals at individual loci, enhance transcriptional risk scores (TRS) that
have recently been shown to provide much greater prediction of disease and progression than genetic risk
scores, and explore the potential of in silico predicted transcriptome-wide association studies in the context
of IBD. These studies will utilize the IBDGC datasets through collaborative arrangements mediated by data
coordinating center. In addition, proof of principle for the use of lipid nanoparticles as an efficient and
specific delivery system for genome editing and/or pharmaceutical delivery to targeted cell types in gut-
derived organoids will be demonstrated. Single cell RNA-Seq will be used to partition variability in gut
epithelial gene expression in the half dozen most common organoid cell types into contributions of the
ethnicity, location of the biopsy, type of disease, and source laboratory. This data will serve as a foundation
for evaluating the effects of a half dozen gene knock-outs across cell types using the lipid nanoparticle
delivery system. All analyses and reagents will be made available to consortium members as expected for
collaborative IBDGC research.
Terms: <Address><Affect><African American><Afro American><Afroamerican><Alleles><Allelomorphs><American><Ancillary Study><Architecture><Area><Assay><Award><Bioassay><Biologic Assays><Biological Assay><Biology><Biopsy><Black Populations><Blood><Blood Reticuloendothelial System><CRISPR><CRISPR method><CRISPR methodology><CRISPR technique><CRISPR technology><CRISPR-CAS-9><CRISPR-based method><CRISPR-based technique><CRISPR-based technology><CRISPR-based tool><CRISPR/Cas method><CRISPR/Cas system><CRISPR/Cas technology><CRISPR/Cas9><CRISPR/Cas9 technology><Cas nuclease technology><Categories><Cell Body><Cell Communication and Signaling><Cell Signaling><Cell-Extracellular Matrix><Cells><Clinical><Clustered Regularly Interspaced Short Palindromic Repeats><Complement><Complement Proteins><Complex><Computer Models><Computer Simulation><Computer based Simulation><Computerized Models><Crohn disease><Crohn's><Crohn's disease><Crohn's disorder><Cytokine Signal Transduction><Cytokine Signaling><DNA><DNA Therapy><Data><Data Coordinating Center><Data Coordination Center><Data Set><Dataset><Deoxyribonucleic Acid><Development><Disease><Disease Progression><Disorder><Drug Delivery><Drug Delivery Systems><Dysfunction><ECM><Engineering / Architecture><Epithelial><Epithelial Cells><Ethnic Origin><Ethnicity><European><Extracellular Matrix><Foundations><Functional disorder><GWA study><GWAS><Gene Expression><Gene Transcription><Gene Transfer Clinical><Genes><Genetic><Genetic Diseases><Genetic Engineering><Genetic Engineering Biotechnology><Genetic Engineering Molecular Biology><Genetic Intervention><Genetic Polymorphism><Genetic Risk><Genetic Transcription><Genetic analyses><Genomic approach><Genomics><Granulomatous Enteritis><Guide RNA><Human><Immune><Immunes><Individual><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Inflammatory Intestinal Disease><Inflammatory Intestinal Disorder><Intestinal><Intestines><Intracellular Communication and Signaling><Investigators><Knock-out><Knockout><Laboratories><Location><Mathematical Model Simulation><Mathematical Models and Simulations><Mediating><Messenger RNA><Mitochondria><Modern Man><Molecular><NIDDK><National Institute of Diabetes and Digestive and Kidney Diseases><Organ Culture><Organ Culture Techniques><Organoids><Outcome><Pathogenesis><Pathology><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pharmaceutical Agent><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Pharmacology><Physiopathology><Play><Predisposition gene><Protocol><Protocols documentation><Quantitative Genetics><RNA Expression><Reagent><Recombinant DNA Technology><Research><Research Personnel><Research Resources><Researchers><Resources><Risk><Risk Assessment><Risk-associated variant><Role><Side><Signal Transduction><Signal Transduction Systems><Signaling><Site><Source><Susceptibility Gene><System><Transcript><Transcription><Translating><Ulcerated Colitis><Ulcerative Colitis><Variant><Variation><aptamer><base><biological signal transduction><black American><bowel><causal allele><causal gene><causal mutation><causal variant><causative mutation><causative variant><cell type><computational modeling><computational models><computational simulation><computer based models><computerized modeling><computerized simulation><developmental><discover genes><eleocolitis><entire genome><full genome><gRNA><gain of function><gene discovery><gene therapy><gene-based therapy><genetic analysis><genetic approach><genetic condition><genetic disorder><genetic manipulation><genetic profiling><genetic therapy><genetically engineered><genome editing><genome sequencing><genome wide association><genome wide association scan><genome wide association studies><genome wide association study><genomewide association scan><genomewide association studies><genomewide association study><genomic editing><genomic effort><genomic strategy><genomic therapy><global gene expression><global transcription profile><improved><in silico><in vitro Organ Culturing><in vitro vertebrate organ culturing><in vivo><knockout gene><lipid nanoparticle><mRNA><member><mitochondrial><nano particle><nano particle delivery><nano-sized particle><nanoparticle><nanoparticle delivered><nanoparticle delivery><nanosized particle><new approaches><novel><novel approaches><novel strategies><novel strategy><pathophysiology><polymorphism><predisposing gene><rectal><regional enteritis><response><response to treatment><risk allele><risk gene><risk genotype><risk loci><risk locus><risk variant><scRNA-seq><single cell RNA-seq><single-cell RNA sequencing><social role><susceptibility allele><susceptibility locus><susceptibility variant><therapeutic evaluation><therapeutic response><therapeutic testing><transcriptome><transcriptomics><treatment response><virtual simulation><whole genome><whole genome association analysis><whole genome association studies><whole genome association study>