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17,054 grants matching “genome editing”
Maintenance and Expansion of the TIGR Annotation Engine Service
$225,000Michelle Gwinn Giglio · University Of Maryland Baltimore · R01 · FY2009 · GM
Development of CRISPR/Cas system for study of trans-sialidase family genes in T. cruzi
$225,000Rick L Tarleton · University Of Georgia · R21 · FY2017 · AI
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** DECADES OF STUDYING PLANT GENE FUNCTION HAVE REVEALED THAT DNA THAT DOES NOT ENCODE PROTEINS IS FAR FROM JUNK DNA, RATHER, IT HAS A STRONG AND WIDESPREAD IMPACT ON PLANT TRAITS. IN CORN, FOR EXAMPLE, GENETIC VARIATION IN NONCODING REGIONS EXPLAINS ON AVERAGE 40% OF THE GENETIC VARIATION ACROSS AGRONOMIC TRAITS. ON A MOLECULAR LEVEL, WE KNOW THAT BINDING BETWEEN SHORT SEGMENTS OF NONCODING DNA AND CERTAIN PROTEINS DICTATES THE EXTENT, TIME AND SPACE AT WHICH A PARTICULAR GENE IS EXPRESSED (OR SILENCED). THERE ARE TENS OF THOUSANDS OF SUCH NONCODING REGULATORY DNA SEGMENTS IN A GENOME THAT POTENTIALLY OPERATE AND INTERACT TO CONTROL GENE EXPRESSION, AND ULTIMATELY, AGRONOMIC TRAITS. WE KNOW THAT VARIATION IN THESE NONCODING DNA ELEMENTS EXPLAINSAGRONOMIC PERFORMANCE, AND THAT TARGETED CHANGES TO SPECIFIC NONCODING SEQUENCES CAN ALTER AGRNOMIC TRAITS SUCH AS YIELD. HOWEVER, PREDICTING PHENTOYPIC OUTCOMES FROM CHANGES TO INDIVIDUAL REGULATORY DNA SEQUENCES REMAINS CHALLENGING. CONSEQUENTLY, OUR LIMITED UNDERSTANDING OF NONCODING DNA LIMITS CROP IMPROVEMENT.THE OVERARCHING GOAL IS TO UNCOVER PUTATIVE REGUALTORY DNA ELEMENTS AS CONSERVED NONCODING SEQUENCES WITHIN GRASS GENOMES, ESTABLISH CORRELATIONS BETWEEN CONSERVED NONCODING SEQUENCE VARIATION AND AWN TRAITS, AND DISSECT THE FUNCTION OF CNSS WITH SUSPECTED ROLES IN AWN TRAITS. TWO PRIMARY QUESTIONS WILL BE ADDRESSED: 1) HOW DOES VARIATION IN CONSERVED NONCODING SEQUENCES RELATE TO AWN TRAITS OVER DEEP EVOLUTIONARY TIME? 2) HOW DO SPECIFIC CONSERVED NONCODING SEQUENCES REGULATE AWN DEVELOPMENT? THE CENTRAL HYPOTHESIS IS THAT AWNS REPEATEDLY EVOLVED IN THE GRASSES VIA CIS-REGULATORY MODIFICATION TO A CONSERVED LEAF BLADE DEVELOPMENTAL PROGRAM. ULTIMATELY, THE PROPOSED WORK WILL UNVEIL PRINCIPLES AND STRATEGIES FOR PRECISELY ENHANCING CROP PLANTS THROUGH TARGETED EDITING OF REGULATORY DNA ELEMENTS.THIS PROJECT AIMS TO DISSECT THE FUNCTION OF SPECIFIC NONCODING DNA ELEMENTS. TO DO SO, I WILL ASK HOW VARIATION IN PUTATIVE REGULATORY DNA ELEMENTS IS CORRELATED WITH IMPORTANT AGRONOMIC TRAITS ACROSS GRASS SPECIES, USING THE GRASS AWN AS AN EXAMPLE. AWNS IMPACT AGRICULTURAL YIELD, PLAYING ROLES IN PHOTOSYNTHESIS, SEED DISPERSAL AND SPROUTING, AND DEFENSE. WHILE MANYGRASSES HAVE AWNS, THEY ARE NOT ESSENTIAL AND ARE THOUGHT TO HAVE ARISEN AT LEAST 12 TIMES INDEPENDENTLY. STRUCTURALLY, AWNS ARE A MODIFIED LEAF BLADE, WHICH ARE PRESENT IN ALL GRASSES, SUGGESTING THAT THE AWN ARISES THROUGH EXPRESSIONOF CONSERVED LEAF BLADE GENES IN A NEW TIME AND PLACE, POSSIBLY THROUGH MODIFICATION OF REGULATORY DNASEQUENCES NEAR GENES KNOWN TO BEREQUIRED TO FORMLEAF BLADES. DESCRIPTIONS OF AWN TRAITS ARE AVAILABLE FOR OVER 11,000 GRASS SPECIES AND THE GENOMES OF APPROXIMATELY 180 GRASS SPECIES HAVE BEEN SEQUENCED,PROVIDING A WEALTH OF PHENOTYPIC AND GENETIC DATA TO ASSOCIATE VARIATION IN NONCODING SEQUENCE WITH SPECIES-LEVEL TRAITS. FURTHERMORE, GENOME EDITING TOOLS ARE AVAILABLE FOR MULTIPLE GRASS SPECIES.FIRST, I WILL USE,CONSERVATORY, A RECENTLY DEVELOPED ALGORITHM, TO GENERATE A COMPREHENSIVE DATABASE OF PUTATIVE REGULATORY DNA ELEMENTS AMONG 180 SEQUENCED GENOMES REPRESENTING GRASS DIVERSITY. SECOND, I WILL ASSOCIATE REGULATORY DNA VARIATION WITH PUBLICLY AVAILABLE AWN PHENOTYPES, FOCUSING ON GENES EXPRESSED IN DEVELOPING AWNS. FINALLY, TO INVESTIGATE THE FUNCTION OF SPECIFIC NONCODING SEQUENCES, I WILL USE GENOME EDITING TO TEST THE FUNCTION OF INDIVIDUAL OR COMBINATIONS OF PUTATIVE REGULATORY DNA SEQUENCES. INITIAL EDITING WILL BE CARRIED OUT IN MAIZE AND BRACHYPODIUM DISTACHYON, WITH A FOCUS ON FIVE CANDIDATE REGULATORY SEQUENCES NEAR A GENE REQUIRED FOR AWN DEVELOPMENT KNOWN AS DROOPING LEAF (DL).
$225,000University Of Massachusetts · · FY2024 · National Institute of Food and Agriculture
**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THE HIGH PATHOGENIC AVIAN INFLUENZA VIRUS, AN INFLUENZA A VIRUS, HAS BEEN A DEVASTATING ISSUE WORLDWIDE, INCLUDING THE OUTBREAK THAT HAS RESULTED IN THE LOSS OF OVER 40 MILLION BIRDS IN THE UNITED STATES IN 2022. ALTHOUGH THE ECONOMIC IMPACT OF THE CURRENT OUTBREAK STILL REMAINS UNDETERMINED, AN OUTBREAK COMES WITH MULTIPLE LAYERS OF ECONOMIC IMPACTS, I.E., THE RECENT 2014-15 OUTBREAK THAT RESULTED IN BILLION-DOLLAR LOSSES TO THE POULTRY INDUSTRY. THE 2014-15 OUTBREAK RESULTED IN THE DEATH OF MORE THAN 50 MILLION BIRDS IN THE U.S. WHICH COMPRISED 12% AND 8% OF THE ANNUAL LAYER AND TURKEY POPULATIONS, RESPECTIVELY. AS A RESULT, APPROXIMATELY 13% OF POULTRY EXPORTS DROPPED DURING THE FIRST HALF OF 2015 DUE TO THE EXPORT BAN ON U.S. PRODUCED POULTRY, WHICH AFFECTED AS MANY AS 233,000 POULTRY FARMS. DEPSITE THE HUGE IMPACTS AND ASTRONOMICAL BIRD LOSSES, THERE REMAINS A LACK OF STRATEGIES AGAINST THE AVIAN INFLUENZA VIRUS (AIV) BEYOND THE PASSIVE BIOSECURITY MEASURES SUCH AS SURVEILLANCE, QUARANTINE, AND PERIMETER DEPOPULATION. FURTHERMORE, THE EMERGENCE OF INFLUENZA A VIRUSES FROM ZOONOTIC RESERVOIRS POSES A GREAT THREAT TO HUMAN HEALTH AND CONTROLLING THE DISEASE IN THE ANIMAL SOURCE IS CRITICAL TO DECREASE RISK TO HUMANS AS INFLUENZA VIRUSES ARE IMPOSSIBLE TO ERADICATE.BASED ON THE CURRENT AND POTENTIAL THREAT OF AIV OUTBREAKS, IT IS URGENT TO DEVELOP BETTER AND MORE ACTIVE STRATEGIES TO LIMIT THE DAMAGE CAUSED BY THE VIRUS. PREVIOUS STUDIES HAVE MOSTLY FOCUSED ON IDENTIFYING AND UNDERSTANDING VIRAL HOST FACTORS RELATED TO HUMAN INFLUENZA A VIRUS (IAV) INFECTION, HOWEVER VERY FEW HAVE FOCUSED ON IDENTIFYING THESE FACTORS IN POULTRY. ON THE MAMMALIAN SIDE, MULTIPLE GENOME-WIDE SCREENING APPROACHES HAVE BEEN EMPLOYED TO IDENTIFY HOST FACTORS INVOLVED IN IAV INFECTION. ALTHOUGH SOME COMMON HITS AND PATHWAYS HAVE BEEN REVEALED, META-ANALYSES HAVE DEMONSTRATED VERY LITTLE OVERLAP IN IDENTIFIED IAV HOST FACTORS WHICH COULD BE DUE TO A NUMBER OF THINGS INCLUDING DIFFERENCESIN STRAINS USED, TIME POINTS ASSAYED AND FUNCTIONAL READOUTS CHOSEN. FURTHERMORE, HOST FACTORS IDENTIFIED IN MAMMALIAN MODELS HAVE VERY LITTLE OR ZERO TRANSLATION TO POULTRY DUE TO THE SMALLER REPERTOIRE OF IMMUNE GENES IN AVIAN SPECIES. THUS, ALTERNATIVE SCREENING STRATEGIES ARE NECESSARY TO UNCOVER HOST FACTORS AND PATHWAYS INVOLVED IN AIV INFECTION IN POULTRY AND THE RECENT ADVANCEMENTS IN CRISPR/CAS9 TECHNOLOGIES PROVIDE A NEW METHOD TO DO THIS.CRISPR SCREENS ARE A POWERFUL SOURCE OF BIOLOGICAL DISCOVERY, ENABLING THE UNBIASED INTERROGATION OF GENE FUNCTION IN A WIDE RANGE OF APPLICATIONS AND SPECIES. IN POOLED CRISPR SCREENS, VARIOUS ENCODED PERTURBATIONS ARE INTRODUCED INTO POOLS OF CELLS THROUGH LENTIVIRAL TRANSDUCTION WHICH ALLOWS US TO INTRODUCE ONE PERTURBATION IN A SINGLE CELL. THE PERTURBED CELLS PROLIFERATE/SURVIVE UNDER A BIOLOGICAL CHALLENGE SUCH AS VIRAL INFECTION. SUBSEQUENTLY, THE PERTURBATION-INDUCED EFFECTS ARE EVALUATED BY NEXT-GENERATION SEQUENCING- BASED IDENTIFI,CATION OF THE GUIDE RNA'S THAT SPECIFY EACH PERTURBATION RESULTING IN A PARTICULAR PHENOYTPE. THE TYPICAL OUTPUT OF SUCH SCREENS ARE RANKED LISTS OF GENES THAT CONFER SENSITIVITY OR RESISTANCE TO THE BIOLOGICAL CHALLENGE OF INTEREST, SUCH AS VIRAL INFECTION. IN ADDITION, IT IS NOW POSSIBLE TO STUDY THE MOLECULAR MECHANISM OF EACH PERTURBATION AT THE SINGLE-CELL LEVEL DUE TO THE DEVELOPMENT OF SINGLE-CELL-BASED TRANSCRIPTOMICS.APPLYING THESE NEW TECHNOLOGIES TO ANIN VITROAVIAN MODEL WILL ALLOW FOR THE STREAMLINED IDENTIFICATION OF THE CANDIDATE HOST FACTORS INVOLVED IN RESISTANCE TO AVIAN INFLUENZA VIRUS. WHILE THESE FACTORS COULD BE IDENTIFIED BY OTHER MOLECULAR BIOLOGY-BASED APPROACHES, SEARCHING FOR VIRAL RESISTANCE HOST FACTORS ONE BY ONE IS BOTH COSTLY AND TIMELY. WE WILL UTILIZE WHOLE-GEMONE KNOCKOUT CRISPR SCREENING TO IDENTIFY CANDIDATE GENE(S) INVOLVED IN AVIAN INFLUENZA RESISTANCE IN ANIN VITROAVIAN CELL CULTURE MODEL AND UTILIZE FUNCTIONAL GENOMICS TO ANNOTATE AND CHARACTERIZE IDENTIFIED HOST FACTORS THAT MAY PLAY A ROLE IN AVIAN INFLUENZA RESISTANCE. THESE EXPERIMENTS WILL PROVIDE FOUNDATIONAL KNOWLEDGE THAT WILL EXPAND OUR KNOWLEDGE IN POTENTIAL CANDIDATE GENE(S) THAT MAY PLAY A ROLE IN AVIAN INFLUENZA RESISTANCE IN THE CHICKEN. IDENTIFICATION OF CANDIDATE GENES AND UNDERSTANDING THEIR FUNCTIONS WILL HELP DEVELOP ANTIVIRAL STRATEGIES AND AID IN THE DEVELOPMENT OF INFLUENZA VIRUS RESILIENT GENOME EDITED CHICKENS.
$225,000The Pennsylvania State University · · FY2023 · National Institute of Food and Agriculture
New Transformation Technology for Gene Editing of Human Mitochondrial DNA Associated With Mitochondrial Diseases
$225,000Hajime Sakai · Napigen, Inc. · R43 · FY2022 · GM
Novel methods to improve nuclease mediated homologous recombination
$225,000Jifeng Zhang · Atgc, Inc. · R41 · FY2017 · GM
Novel reporter cell lines for neurotoxicant assays
$225,000Eric M Ostertag · Hera Testing Laboratories, Inc. · R43 · FY2014 · ES
Define the role of NUCKS1 in homologous recombination DNA repair and cancer biology
$225,000Claudia Wiese · Colorado State University · R56 · FY2019 · ES
A 3D osteoarthritis model targeting patient populations with high risk genetic polymorphisms
$225,000Vincent P Willard · Cytex Therapeutics Inc. · R43 · FY2017 · AR
Biosynthesis of novel and natural plant alkaloid compounds for drug production and discovery
$225,000Kristy Hawkins · Antheia, Inc. · R43 · FY2017 · AT
Comprehensive Solution for Transcriptome Profiling of Archived Tissues
$225,000Brian Clifton Haynes · Asuragen, Inc. · R43 · FY2014 · ES
Genetic toolkit for genome editing of the Lactobacillus genus.
$224,999Ewa Lis · Koliber Biosciences, Inc. · R43 · FY2018 · GM
Nanobodies for detecting and manipulating A to I editing enzymes and their modified RNA products
$224,975Hiep T Tran · Abzyme Therapeutics, Llc · R43 · FY2014 · DA
Assay of chemicals for Parkinsonâs toxicity in human iPSC-derived neurons
$224,926Patrick M McDonough · Vala Sciences, Inc. · R43 · FY2015 · ES
Development of a cannabinoid yeast factory: improving geranyl pyrophosphate production through metabolic engineering
$224,920Anthony Neal Farina · Librede, Inc. · R43 · FY2016 · GM
The Role of Non-Coding RNA Editing in MET Signaling in NSCLC
$224,918Mario Acunzo · Virginia Commonwealth University · R21 · FY2023 · CA
A Platform Technology for High-Throughput Screening of Gene Regulatory Elements
$224,881Gregory E Crawford · Element Genomics, Inc. · R41 · FY2016 · GM
Development of mitochondrial disease mouse models
$224,856Neil Otto · B-Mogen Biotechnologies, Inc. · R41 · FY2018 · OD
Targeted Gene Insertion by Directed Evolution of ΦC31 Integrase for Therapeutic Gene Editing
$224,854Ruby Yanru Chen-Tsai · Applied Stemcell, Inc. · R44 · FY2020 · GM
Genetic Modification of the Rabbit for Development of Single Chain Antibodies
$224,850Thomas Zeyda · Ingenious Targeting Laboratory, Inc. · R43 · FY2019 · AI
Mechanism of APBB2 contributions to glaucoma
$224,797Michael G Anderson · University Of Iowa · R21 · FY2021 · EY
Project 4 Genetic Variation of Murine Serotonergic Phenotypes
$224,776Elaine Sanders Bush · Vanderbilt University · P50 · FY2009 · MH
Project 4 Genetic Variation of Murine Serotonergic Phenotypes
$224,776Elaine Sanders Bush · Vanderbilt University · P50 · FY2008 · MH
Development and Characterization of a Preclinical Swine Model of Osteogenesis Imperfecta
$224,773Adrienne Leigh Watson · Recombinetics, Inc. · R43 · FY2019 · DE
Genome-wide CRISPR screen to identify pro-myogenic factors for cell therapy of DMD
$224,725Louis M Kunkel · Myofinity Biosciences Inc · R41 · FY2018 · AR