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17,054 grants matching “genome editing”
Miniaturized AD/ADRD Microphysiological Systems Platform for High-throughput Screening
$500,000Wayne W Poon · Neucyte, Inc. · R41 · FY2023 · AG
COMPARATIVE EVALUATION OF THE PHENOTYPE, GENOME AND ANIMAL PRODUCTS DERIVED FROM OFFSPRING OF A GENOME EDITED, HORNLESS BULL AND CONTROLS.
$500,000University Of California, Davis · · FY2017 · National Institute of Food and Agriculture
CAREER: Nanoparticle-mediated genome engineering of plants and plastids
$500,000Markita P Landry · University Of California-Berkeley · · FY2021 · ENG
**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** GENE EDITING TECHNOLOGY PROVIDES A POWERFUL TOOL FOR SITE-SPECIFIC MANIPULATING OF DNA METHYLATION FOR CROP IMPROVEMENT, BUT ITS UNINTENDED EFFECTS ARE NOT WELL STUDIED. BETTER UNDERSTANDING OF ITS UNINTENDED EFFECTS ON DNA METHYLATION WILL ENCOURAGE ITS USE FOR DEVELOPING NEW CROPS THAT ARE MORE NUTRITIOUS AND MORE PRODUCTIVE.THIS PROJECT AIMS TO STUDY THE UNINTENDED EFFECTS OF CRISPR/DCAS-MEDIATED EDITING OF DNA METHYLATION IN TOMATO. TOMATO IS ONE OF THE MOST POPULAR AND NUTRITIOUS FOOD PRODUCTS AND ALSO ITS FRUIT QUALITY ATTRIBUTES ARE LARGELY INFLUENCED BY DNA METHYLATION EVENTS. WE WILL USE A CRISPR/DCAS-DNA METHYLTRANSFERASE SYSTEM TO PRODUCE SITE-SPECIFIC DNA METHYLATION-EDITED TOMATO PLANTS AND ALSO TO PRODUCE TOMATO PLANTS USING CONVENTIONAL TISSUE CULTURE IN-VITRO REGENERATION AND GENETIC TRANSFORMATION TECHNIQUES. TOMATO FRUITS FROM THESE PLANTS WILL BE USED FOR WHOLE GENOME BISULFITE SEQUENCING, RNA-SEQ, FRUIT QUALITY AND OTHER PHENOTYPIC ANALYSES. WE WILL CONDUCT A SIDE-BY-SIDE COMPARISON FOR THE UNINTENDED EFFECTS GENERATED FROM USING CONVENTIONAL PLANT TISSUE CULTURE, GENETIC TRANSFORMATION AND GENE EDITING TECHNOLOGIES.THE PROJECT GOAL IS CLOSELY ALIGNED WITH THE BRAG PROGRAM AREA 5F: COMPARISON OF THE TYPES AND FREQUENCIES OF NUCLEIC ACID CHANGES INTRODUCED INTO IMPORTANT CROP GENOMES, VIA GENETIC ENGINEERING TECHNIQUES VERSUS OTHER PLANT BREEDING TECHNIQUES. THE KNOWLEDGE GENERATED FROM THIS STUDY WILL AID PLANT BREEDERS PRACTICING DNA METHYLATION EDITING IN CROPS, AND FACILITATE THE POLICY- AND DECISION-MAKING PROCESS AT FEDERAL REGULATORY AGENCIES. WE WILL ALSO INCORPORATE THE SCIENCE-BASED KNOWLEDGE GENERATED FROM THIS PROJECT INTO OUR PUBLIC EDUCATION EFFORTS TO IMPROVE SOCIETY'S UNDERSTANDING ABOUT THE GENE EDITING TECHNOLOGY.
$500,000University Of Connecticut · · FY2021 · 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.** PLANT RHABDOVIRUSES REPRESENT THE NEXT GENERATION OF VIRAL VECTORS FOR DELIVERY OF PROTEINS AND RNAS TO PLANTS AND INSECTS. BECAUSE OF THEIR LARGE CARRYING CAPACITY, THERE IS SIGNIFICANT INTEREST IN USING RHABDOVIRUSES FOR GENOME EDITING. RHABDOVIRUSES REPLICATE IN THEIR PLANT HOSTS AND INSECT VECTORS, THUS CREATING A COMPLEX OPPORTUNITY FOR UNDERSTANDING RISKS ASSOCIATED WITH USING THESE TYPES OF VIRUSES AS DELIVERY SYSTEMS. WE PROPOSE TO USE OUR RECENTLY DEVELOPED INFECTIOUS CLONE FOR MAIZE MOSAIC VIRUS (MMV) AS A MODEL FOR UNDERSTANDING RISKS ASSOCIATED WITH RHABDOVIRUS VECTORS. WE WILL CHARACTERIZE THE ENVIRONMENTAL RISK FOR VECTOR TRANSMISSION OF GENETICALLY MODIFIED MMV TO AGRONOMIC AND WILD GRASS SPECIES (FAMILY POACEAE). WE WILL STUDY VIRUS RECOMBINATION OF THE GENETICALLY MODIFIED VIRUS TO DETERMINE THE POTENTIAL FOR GENETIC EXCHANGE BETWEEN MODIFIED MMV AND WILDTYPE (WT) MMV. TO REDUCE RISK OF VIRUS ESCAPE AND INCREASE UTILITY IN THE FIELD WE WILL CREATE REDUCED-RISK VIRAL VECTORS THAT ARE COMPETENT FOR PLANT INFECTION BUT ARE NO LONGER INSECT TRANSMISSIBLE. THE PROJECT OUTCOMES WILL PROVIDE FEDERAL REGULATORY AGENCIES WITH IMPORTANT INFORMATION ABOUT THE SPECIFIC HOST RANGE OF MMV AND THE UTILITY OF THIS SPECIFIC VIRUS VECTOR. THE PROJECT TEAM IS WELL EQUIPPED TO CONDUCT THE PROPOSED RESEARCH WITH GENETICALLY MODIFIED VIRUSES AND VECTORS AND ALL WORK WILL BE CONDUCTED IN PROPER CONTAINMENT FACILITIES AND WITH APPROPRIATE PERMITS.
$500,000North Carolina State University · · FY2022 · National Institute of Food and Agriculture
KNOWLEDGE OF THE GENETICS AND MECHANISMS OF PEST RESISTANCE IS URGENTLY NEEDED TO ASSESS AND MANAGE THE RISK OF RESISTANCE FOR WIDELY ADOPTED TRANSGENIC BT CROPS, YET THIS INFORMATION IS LACKING FOR HELICOVERPA ZEA (CORN EARWORM, CEW), ONE OF THE MOST ECONOMICALLY IMPORTANT CROP PESTS IN THE UNITED STATES. SOME POPULATIONS OF THIS PEST HAVE EVOLVED RESISTANCE TO CRY1 AND CRY2 TOXINS CURRENTLY DEPLOYED IN BT CROPS, AND VIP3AA REMAINS THE ONLY BT TOXIN IN MULTI-TOXIN BT CORN AND COTTON THAT IS HIGHLY EFFECTIVE AGAINST POPULATIONS OF THIS PEST IN SEVERAL REGIONS.TO IMPROVE KNOWLEDGE ON PEST RESISTANCE TO CROPS PRODUCING VIP3AA, THIS PROJECT WILL USE A GENOME WIDE ASSOCIATION STUDY, HIGH-RESOLUTION MAPPING, RNA SEQUENCING, AND CRISPR/CAS9 GENE EDITING TO IDENTIFY GENES CONFERRING RESISTANCE TO VIP3AA IN CEW. BY DEVELOPING GENOMIC TOOLS FOR MOLECULAR DETECTION OF VIP3AA RESISTANCE IN CEW, WE WILL ENHANCE RESISTANCE RISK ASSESSMENT AND MANAGEMENT FOR CEW AND PROVIDE NEW TOOLS FOR PRESERVING EFFICACY OF BT CROPS IN THE U.S. SPECIFICALLY, WE WILL IDENTIFY GENES CONFERRING RESISTANCE TO VIP3AA IN LAB- AND FIELD-SELECTED POPULATIONS OF CEW AND COMPARE THE RESISTANCE GENES BETWEEN THE LAB- AND FIELD-SELECTED POPULATIONS. WE WILL CONFIRM THE ROLE OF IDENTIFIED GENES BY USING CRISPR/CAS9 GENE EDITING TO CREATE KNOCKOUT MUTATIONS IN A VIP3AA-SUSCEPTIBLE STRAIN THAT DISRUPT CANDIDATE RESISTANCE GENES FOR VIP3AA. THE NEW KNOWLEDGE ON GENES CONFERRING RESISTANCE TO VIP3AA WILL BE USED TO TRACK THE FREQUENCY OF ALLELES CONFERRING RESISTANCE TO VIP3AA OVER FOUR YEARS ACROSS CEW POPULATIONS FROM FIVE STATES (AR, LA, MS, TN AND TX) WHERE THE RESISTANCE RISK IS HIGH.THIS PROJECT WILL FACILITATE REGULATOR'S DECISIONS IN RESPONSE TO EVOLUTION OF PEST RESISTANCE TO BT CROPS. THIS RESEARCH SHOULD CONTRIBUTE IN MAINTAINING THE DURABILITY OF BT TRAITS AND THUS BENEFIT GROWERS AND SEED PROVIDERS. THE NOVEL TECHNIQUES DEVELOPED AND FUNDAMENTAL KNOWLEDGE GAINED IN THIS PROJECT MAY HAVE IMMEDIATE AND BROAD APPLICATIONS FOR MONITORING AND MANAGING RESISTANCE IN OTHER SYSTEMS, AND THUS BENEFIT OTHER SCIENTISTS/RESEARCHERS. WE ANTICIPATE THAT TWO POST-DOCS (ONE INDIVIDUAL FOR ONE YEAR; THE OTHER FOR SEVERAL MONTHS) AND SEVERAL UNDER GRADUATE STUDENTS (TWO PER YEAR, 10 H PER WEEK) WILL BE INVOLVED IN THIS RESEARCH AND RECEIVE TRAINING IN ENTOMOLOGY AND MOLECULAR ASPECTS OF BT RESISTANCE.
$500,000University Of Arizona · · FY2020 · National Institute of Food and Agriculture
THE PRODUCTION EFFICIENCY CAN BE ENHANCED FOR THE CATFISH INDUSTRY THROUGH THE APPLICATION OF MONO-SEX CULTURE SYSTEM, BECAUSE CATFISH MALES GROW FASTER THAN FEMALES BY ~ 60%. HOWEVER, IT HAS NOT BEEN POSSIBLE TO TAKE ADVANTAGE OF SUCH SEX DIMORPHISM BECAUSE OF THE LACK OF INFORMATION NEEDED TO DEVELOP THE SEX MANIPULATION TECHNOLOGIES. OUR OVERARCHING HYPOTHESIS IS THAT SEX-SPECIFIC EXPRESSION OF CERTAIN GENES WITHIN THE SEX DETERMINATION REGION ARE AFFECTED BY EPIGENETIC DNA MODIFICATIONS, WHICH IN TURN, DETERMINES CATFISH SEX. IN THIS PROJECT, WE WILL TEST THIS HYPOTHESIS BY ACHIEVING THE FOLLOWING SPECIFIC OBJECTIVES: 1) DETERMINE THE SEX-SPECIFIC EPIGENETIC MODIFICATIONS (METHYLATION) IN GENETIC MALES AND FEMALES DURING EARLY SEX DIFFERENTIATION; 2) DETERMINE THE INVOLVEMENT OF SUCH EPIGENETIC MODIFICATIONS IN REGULATION AND SEX-SPECIFIC EXPRESSION OF GENES WITHIN THE SEX DETERMINATION REGION; 3) DETERMINE THE INVOLVEMENT OF EPIGENETIC MODIFICATIONS IN TEMPERATURE-INDUCED SEX REVERSAL; AND 4) FUNCTIONAL ANALYSIS OF THE SEX DETERMINATION CANDIDATE GENE (BCAR1) IN CATFISH THROUGH KNOCKOUT AND GENOME EDITING. ACHIEVING THESE GOALS WILL ALLOW US TO LEARN ABOUT MOLECULAR MECHANISMS OF SEX DETERMINATION IN CATFISH, PROVIDING INFORMATION FOR SEX MANIPULATION IN CATFISH. SUCH INFORMATION WILL DESIGNING OF STRATEGIES TO DEVELOP MONOSEX TECHNOLOGIES FOR CATFISH AQUACULTURE. IN THE LONG TERM, THIS WORK WILL PROVIDE INFORMATION FOR MORE EFFICIENT PRODUCTION OF CATFISH, ENHANCING PRODUCTION AND PROFIT MARGINS FOR THE US CATFISH INDUSTRY. ?
$500,000Syracuse University · · FY2019 · National Institute of Food and Agriculture
DUE TO EASE OF USE, CRISPR-CAS9 HAS ADVANCED REMARKABLY IN THE PAST FEW YEARS AND HAS BECOME A UBIQUITOUS GENOME-EDITING METHOD BEING APPLIED TO AN INCREASING NUMBER OF SPECIES. WHILE SEVERAL SUCCESSFUL CASES OF CROP IMPROVEMENT USING VARIOUS GENOME- EDITING PLATFORMS INCLUDING CRISPR SYSTEMS AND TALENS HAVE BEEN REPORTED, CONCERNS OF GENOME WIDE OFF-TARGETS HAVE NOT BEEN THOROUGHLY ADDRESSED. TREMENDOUS PROGRESS HAS BEEN MADE IN INCREASING THE SPECIFICITY AND THUS REDUCING OFF-TARGETING BY ENGINEERING CAS9 VARIANTS SUCH AS THE HYPER-ACCURATE CAS9 VARIANT, AN ALTERNATIVE CRISPR-CPF1 SYSTEM ANALOGOUS TO CRISPR-CAS9, AND A NEW BASE EDITING APPROACH, WHICH DOESN'T REQUIRE DNA CLEAVAGE TO INCORPORATE SPECIFIC MUTATIONS. REGULATORY AGENCIES NEED TO EVALUATE THE PRECISION OF THESE NEW AND EMERGING GENE- EDITING REAGENTS. WE PROPOSE TO USE THE CURRENT AND EMERGING GENOME-EDITING REAGENTS FOR TARGETED MUTAGENESIS OF COMMERCIALLY IMPORTANT CANDIDATE GENES IN TWO DIFFERENT CROP SPECIES, POTATO AND CAMELINA, WHICH HAVE CONTRASTING GENOMIC ARCHITECTURE AND MODES OF REPRODUCTION. IN POTATOMECHANICALDAMAGE TOTUBERS DURING HARVEST AND POST-HARVEST PROCEDURES LEAD TO DISCOLORATION DUE TO ENZYMATIC BROWNING CAUSED BY THE CANDIDATE GENEPOTATO POLYPHENOL OXIDASE (PPO). PPO CATALYZES THE CONVERSION OF O-DIHYDROXYPHENOLS TO O-QUINONES. THE QUINONES POLYMERIZE AND REACT WITH AMINO ACIDS RESULTING IN THE FORMATION OF BLACK/BROWN PIGMENTATION. OUR SECOND CANDIDATE GENE, DELTA-12-DESATURASE (FAD2) CONVERTS OLEIC ACID (18:1) FATTY ACID TO 18:2. BY KNOCKING OUTFAD2 WE RETAIN HIGH OLEIC ACID WHICH IS DESIRABLE IN INDUSTRIAL OILS.WE WILL COMPARE THE GENOME WIDE OFF-TARGET EFFECTS CAUSED BY THESE REAGENTS USING WHOLE GENOME SEQUENCING AND DETERMINE THE TYPE AND FREQUENCY OF ON- AND OFF-TARGET VARIATION ATTRIBUTABLE BY GENOME-EDITING REGEANTS. THIS STUDY WOULD PROVIDE A COMPREHENSIVE RISK ASSESSMENT OF GENOME- EDITED CROPS WITH CURRENT TECHNOLOGIES. THIS PROPOSAL ADDRESSES THE BRAG FOCUS AREA OF COMPARISON OF THE TYPES AND FREQUENCIES OF NUCLEIC ACID CHANGES INTRODUCED INTO IMPORTANT CROP GENOMES, VIA GENETIC INSERTION/MODIFICATION TECHNIQUES VERSUS OTHER PLANT BREEDING TECHNIQUES - OFF TARGET EFFECTS OF GENOME-EDITING TECHNOLOGIES.
$500,000Michigan State University · · FY2018 · National Institute of Food and Agriculture
EDGE CMT: Dissecting complex traits in wild isolates of yeast by high-throughput genome editing
$500,000Lars M Steinmetz · Stanford University · R01 · FY2022 · HG
SORGHUM IS A MAJOR RESOURCE EFFICIENT CROP WITH IMMENSE POTENTIAL FOR EXPANDED PRODUCTION AS A GLUTEN-FREE SOURCE OF CALORIES AND PROTEIN IN U.S. AND WORLDWIDE. HOWEVER, THE DOMINANT ACCUMULATION OF KAFIRIN STORAGE PROTEINS IN THE KERNELS RESULTS IN GRAIN WITH LOW LEVELS OF LYSINE AND PROTEIN WITH POOR DIGESTIBILITY. KAFIRINS ARE DEVOID OF LYSINE, AN ESSENTIAL AMINO ACID IN THE DIETS OF HUMANS AND MONO-GASTRIC LIVESTOCK. THE POOR PROTEIN QUALITY AND PROTEIN AVAILABILITY SIGNIFICANTLY LIMIT THE CURRENT VALUE OF SORGHUM AS A PROTEIN SOURCE FOR HUMANS AND LIVESTOCK. TO SOLVE BOTH OF THESE LIMITATIONS, AND ALLOW BETTER REALIZATION OF SORGHUM'S AGRONOMIC ADVANTAGES, THE PI APPLIED CRISPR/CAS9, A STATE-OF-THE-ART GENE EDITING APPROACH, IN WHICH THE WHOLE, 20 MEMBER K1C ALPHA-KAFIRIN STORAGE PROTEIN GENE FAMILY WAS TARGETED FOR SUPPRESSION USING A SINGLE GUIDE RNA. CRISPR/CAS9 HAS THE GAME-CHANGING ADVANTAGE OF BEING ABLE TO PRODUCE NON-TRANSGENIC END-PRODUCTS WHICH ALLOWS RAPID UTILIZATION OF THE PRODUCTS FOR HUMAN AND ANIMAL NUTRITION. THE WORK ALREADY DEMONSTRATED PROOF-OF-CONCEPT BY GENERATING SORGHUM LINES WITH REDUCED KAFIRINS, AND INCREASED NON-KAFIRINS THROUGH THE PROCESS OF PROTEOME REBALANCING. THIS RESULTED IN LINES WITH INCREASED LYSINE, PROTEIN DIGESTIBILITY AND TOTAL PROTEIN IN THE GRAIN.THE PROJECT INVOLVES CROSSING THE KAFIRIN GENE EDITED LINES TO SORGHUM LINES WITH AND WITHOUT THE WAXY, HIGH AMYLOPECTIN TRAIT CONFERRED BY A MUTATION IN THE WAXY1 GENE ENCODING GRANULE BOUND STARCH SYNTHASE. THERE IS EVIDENCE THAT BOTH THE HIGH PROTEIN DIGESTIBILITY TRAIT AND THE HIGH AMYLOPECTIN TRAIT, WHICH CAN INCREASE STARCH SOLUBILITY, CAN ALONE AND ADDITIVELY IMPROVE THE DOUGH-MAKING CHARACTERISTICS OF SORGHUM FLOUR. THE WORK WILL CHARACTERIZE THE VARIOUS PARAMETERS OF DOUGH QUALITY OF THE HIGH AMYLOPECTIN LINES. THE NEXT PHASE OF THE PROJECT WILL REMOVE THE TRANSGENE, CURTAILING FURTHER KAFIRIN EDITING AND LEAVING BEHIND JUST THE BENEFICIAL REDUCED KAFIRIN PHENOTYPE. GENOMIC DNA SEQUENCING AND RNA-SEQUENCING WILL BE USED TO CHARACTERIZE THE STABLE KAFIRIN EDITS AND DETERMINE THEIR EFFECTS ON EXPRESSION OF INDIVIDUAL K1C KAFIRIN FAMILY GENES.RNA-SEQUENCING WILL ALSO BE USED TO ASSESS THE NATURE AND REGULATION OF THE INCREASE IN THE NON-KAFIRIN GENES WHICH LEAD TO PROTEOME REBALANCING EFFECT AND IMPROVED GRAIN NUTRITIONAL QUALITY. OTHER METHODS WILL BE USED TO ASSESS IF EPIGENETIC FACTORS SUCH AS GENOME METHYLATION AND CHROMATIN ACCESSIBILITY ARE INVOLVED IN GENE EXPRESSION CHANGES THAT LEAD TO PROTEOME REBALANCING. THESE DATA WILL BE RELEVANT TO MORE GENERAL STUDIES AIMED AT DISSECTING NITROGEN UTILIZATION DURING SEED STORAGE PROTEIN ACQUISITION.AFTER TRANSGENE-FREE LINES WITH OPTIMAL KAFIRIN EDITS ARE IDENTIFIED, FURTHER SELECTIONS WILL BE MADE USING LARGE-SCALE FIELD TRIALS WHICH WILL LIKELY CONFIRM THAT ALTERING THE SEED PROTEOME BALANCE DOES NOT HAVE ADVERSE PLANT PERFORMANCE OR YIELD EFFECTS. THE FINAL PHASE WILL BE TO CONFIRM SMALL-SCALE PREVIOUS IN VITRO RESULTS IN ONE EDITED LINE, WITH AND WITHOUT INTROGRESSION OF THE WAXY TRAIT, BY CONDUCTING MONO-GASTRIC ANIMAL PROTEIN DIGESTIBILITY ASSAYS AND FEEDING STUDIES USING PIGS AS THE MODEL SYSTEM. WHILE CONCEPTUALLY STRAIGHTFORWARD, THIS WORK WILL TAKE SOME TIME. THE PROJECT WILL EFFECT A PLAN FOR ACHIEVING THE GOALS AND DELIVERING A FINISHED PRODUCT WITHIN A THREE-YEAR TIMESCALE.
$500,000Board Of Regents Of The University Of Nebraska · · FY2021 · 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 US CARROT CROP HAS AN ANNUAL VALUE OF $863 MILLION. CARROTS ARE THE 7TH MOST CONSUMED FRESH VEGETABLE IN THE US, AND THE US IS THE 4TH LARGEST PRODUCER OF CARROTS IN THE WORLD. CARROT IS WIDELY RECOGNIZED FOR ITS CONTRIBUTIONS TO HUMAN HEALTH THROUGH THE HIGH CONTENT OF PROVITAMIN A Β-CAROTENE IN ITS ROOT. THE PRODUCTION OF SUNFLOWERS FOR BOTH OIL AND NON-OIL PURPOSES HAS AN ANNUAL VALUE OF >$350 MILLION. SUNFLOWER IS ALSO THE #4 OIL CROP PRODUCED GLOBALLY. THE SUSTAINED COMMERCIAL INTEREST IN SUNFLOWER IS BASED IN LARGE PART BECAUSE OF THE INTRODUCTION OF HIGH- AND MID-OLEIC ACID OIL GERMPLASM THAT IS HIGHLY DESIRED FOR THE MANUFACTURE OF TRANS FAT-FREE BAKED AND FRIED FOODS.PLANTS ARE MASTER MANUFACTURERS OF USEFUL CHEMICALS, OR NATURAL PRODUCTS, THAT THEY NORMALLY USE TO PROTECT THEMSELVES AGAINST HERBIVORES AND MICROBIAL PATHOGENS, OR TO ATTRACT POLLINATORS. NATURAL PRODUCTS ACCOUNT FOR ONE-THIRD OF ALL FOOD AND DRUG ADMINISTRATION-APPROVED NOVEL DRUGS OR NEW MOLECULAR ENTITIES (NMES); 25% OF THESE ARE DERIVED FROM PLANTS. SIMILARLY, 11% OF THE 252 DRUGS CONSIDERED ESSENTIAL BY THE WORLD HEALTH ORGANIZATION ORIGINATED FROM FLOWERING PLANTS. DESPITE THEIR PREVALENCE AS THE SOURCE OF NUMEROUS PHARMACEUTICALS, THE ENTIRE SUITE OF BIOCHEMICAL MACHINERY NECESSARY FOR THE SYNTHESIS OF RELATIVELY FEW NATURAL PRODUCTS HAS BEEN IDENTIFIED.ONE IMPORTANT CLASS OF PLANT-DERIVED NATURAL PRODUCTS IS THE FALCARINS. FALCARINS ARE KNOWN TO ORIGINATE FROM LIPIDS FOUND IN ESSENTIALLY ALL LIVING ORGANISMS BUT THEIR SYNTHESIS IS RESTRICTED TO A HANDFUL OF PLANT FAMILIES WHICH INCLUDE FRESH-MARKET AND PROCESSING CROPS SUCH CARROTS AND OILSEEDS LIKE SUNFLOWER. FALCARINS ARE KNOWN FOR THEIR HEALTH PROMOTING, ANTI-CANCER AND ANTIMICROBIAL ACTIVITIES AND ARE THOUGHT TO BE CRITICAL FOR PLANT DEFENSE AGAINST AGRONOMICALLY-DEVASTATING PATHOGENS. ADDITIONALLY, SPECIFIC FALCARINS ARE KNOWN TO BE A COMPONENT OF THE BITTER TASTE OF CARROTS. DESPITE KNOWLEDGE OF THEIR EXISTENCE IN PLANTS FOR MORE THAN 50 YEARS, ONLY MODERATE PROGRESS HAS BEEN MADE ON UNDERSTANDING HOW PLANTS MAKE FALCARINS, WHICH IN TURN HAS RESULTED IN LITTLE IF ANY EMPHASIS ON THE USE OF THESE NATURAL PRODUCTS IN CROP IMPROVEMENT EFFORTS.THE GOAL OF THE PROPOSED RESEARCH IS TO FULLY IDENTIFY AND CHARACTERIZE THE BIOCHEMICAL MACHINERY THAT PLANTS USE TO MAKE FALCARINS USING CARROT AND SUNFLOWER AS AGRONOMICALLY-RELEVANT PLANT SPECIES. TO ACCOMPLISH THIS, CUTTING-EDGE GENOMICS AND GENOME EDITING TECHNIQUES, SUCH AS CRISPR, WILL BE EMPLOYED. THROUGH THIS WORK, CARROT GERMPLASM WITH ALTERED FALCARIN CONTENT AND COMPOSITION WILL BE GENERATED. THE GERMPLASM AND INFORMATION GENERATED THROUGH THIS RESEARCH WILL PROVIDE A VALUABLE RESOURCE FOR PLANT BREEDING EFFORTS AIMED AT IMPROVING CROP RESILIENCE, ENHANCING FLAVOR PROFILES, AND IMPROVING THE NUTRITIONAL QUALITY OF CARROTS THAT WILL TRANSLATABLE TO OTHER CROP SPECIES. THIS RESEARCH FURTHER STANDS TO ELEVATE THE IMPORTANCE OF FALCARINS FOR HUMAN HEALTH,AS ANTI-CANCER COMPONENTS THAT PROVIDE ADDED VALUE AND BENEFITS TO CARROT AND SUNFLOWER PRODUCTION AND CONSUMPTION. GIVEN THE DEMONSTRATED HEALTH-PROMOTING PROPERTIES OF FALCARINS, WE ENVISION THAT THIS RESEARCH WILL ADVANCE THE USE OF CARROT IN FUNCTIONAL FOOD APPLICATIONS, A GROWING SEGMENT OF THE FOOD MARKET.
$500,000Board Of Regents Of Nevada System Of Higher Education · · FY2021 · National Institute of Food and Agriculture
Center for Functional Validation and Evaluation of ENCODE Enhancer Regions
$500,000Barbara E Stranger · University Of Chicago · UM1 · FY2018 · HG
Enhancing Animal Care in a New High-Throughput Rodent Behavior Analysis Core Facility
$500,000Serge E Przedborski · Columbia University Health Sciences · G20 · FY2016 · OD
FMSG: Bio: Advancing Extracellular Vesicle Biomanufacturing of CRISPR-Edited Human iPSC-derived MSCs with Next-Generation Purification
$500,000Zhen Ma · Syracuse University · · FY2023 · BIO
CAREER: Smartphone-Based CRISPR Biosensor for Point-of-Care HIV Viral Load Testing
$500,000Qingshan Wei · North Carolina State University · · FY2020 · ENG
Functions and mechanisms of A-to-I RNA editing in Fusarium graminearum
$500,000Jin-Rong Xu · Purdue University · · FY2018 · BIO
NanoLuciferase-based AD/ADRD Microphysiological Systems Platform for High-throughput Screening
$500,000Wayne W Poon · Neucyte, Inc. · R41 · FY2024 · AG
Advancing Transfer RNA Discovery, Research and Resources
$500,000Todd Michael Lowe · University Of California Santa Cruz · R01 · FY2012 · HG
III:Small:Algorithms for Tandem Repeat Variant Discovery Using Next Generation Sequencing Data
$500,000Gary Benson · Trustees Of Boston University · · FY2010 · CSE
Neonatal Research Network Data Coordinating Center (DCC)
$499,999Abhik Das · Research Triangle Institute · U10 · FY2017 · HD
Systematic identification of oncogenic KRAS synthetic lethal interactions
$499,996William C Hahn · Broad Institute, Inc. · U01 · FY2019 · CA
Development of a nanoparticle-based gene editing technology for neurological applications
$499,996Krystof S Bankiewicz · Ohio State University · UH3 · FY2022 · NS
National Swine Resource and Research Center 1
$499,943Randall S Prather · University Of Missouri-Columbia · U42 · FY2020 · OD
GENETIC MODIFICATION (GM) TECHNOLOGY SHOWS PROMISING RESULTS FOR INCREASING NUTRITIONAL QUALITY AND YIELD OF CROPS. MORE RECENTLY, GENOME EDITING (GE) TECHNOLOGY USING CRISPR (CLUSTERED REGULARLY INTERSPERSED SHORT PALINDROMIC REPEATS) ASSOCIATED CAS9/SGRNA SYSTEM SHOWS GREAT POTENTIAL FOR CROP IMPROVEMENT. HOWEVER, CONSUMERS HARBOR NEGATIVE VIEWS TOWARD GM AND GE FOOD PRODUCTS. CONSUMER CONCERNS INCLUDE THE POTENTIAL FOR GENOMIC VARIANTS AND UNPREDICTABLE PHENOTYPIC CONSEQUENCES DUE TO THE INSERTION OF A TRANSGENE OR OFF-TARGET MUTATIONS GENERATED BY CRISPR/CAS9. MODERN NON-TRANSGENIC PLANT BREEDING TECHNIQUES (E.G., IRRADIATION OR CHEMICAL MUTAGENESIS, TISSUE CULTURE, SOMATIC HYBRIDIZATION, AND WIDE CROSSING) ARE USED ON A WIDE SCALE, AND MORE THAN 2,000 CROP VARIETIES DERIVED FROM MODERN NON-TRANSGENIC PLANT BREEDING TECHNIQUES HAVE ENTERED THE FOOD SUPPLY WITHOUT SPECIFIC SAFETY REGULATIONS. HOWEVER, THESE TECHNIQUES ALSO CREATE A VARIETY OF PLANT GENOME MUTATIONS THAT ARE COMPARABLE TO THOSE CREATED BY TRANSGENIC AND GENE EDITING PLANT BREEDING, AND IT IS STILL QUESTIONABLE WHETHER THESE MUTATIONS ARE OF A SIMILAR MAGNITUDE AND TYPE TO THOSE INTRODUCED BY GM AND GE PLANT BREEDING METHODS.USING TOMATO, WHICH IS ONE OF THE HIGHEST PRODUCED EDIBLE CROPS IN THE WORLD AND IS AN EXCELLENT MODEL PLANT FOR THE STUDY OF COMPARATIVE GENOMICS AND PHENOMICS, THE GOAL OF THIS STUDY IS TO COMPARE AND CONTRAST THE TYPES AND FREQUENCIES OF GENOMIC CHANGES ASSOCIATED WITH UNINTENDED PHENOTYPIC VARIATIONS RESULTING FROM CRISPR/CAS9-MEDIATED GENOME-EDITED TOMATO VERSUS EMS-MUTAGENIZED TOMATO, AS WELL AS TRANSGENIC TOMATO VERSUS TISSUE CULTURE-DERIVED NON-TRANSGENIC TOMATO. THE SPECIFIC OBJECTIVES ARE PROPOSED: WE WILL 1) GENERATE CRISPR/CAS9-MEDIATED PURPLE-KNOCKOUT TOMATO LINES AND EMS-MUTAGENIZED PURPLE-LOSS TOMATO LINES; 2) PERFORM WHOLE GENOME SEQUENCING IN THE CRISPR/CAS9-MEDIATED PURPLE-KNOCKOUT LINES AND EMS-MUTAGENIZED PURPLE-LOSS LINES, ALONG WITH TRANSGENIC PURPLE-MONITORING TOMATO LINES EXPRESSING DEL/ROS1 TRANSGENE AND TISSUE CULTURE-DERIVED NON-TRANSGENIC LINES WHICH ARE NOT ASSOCIATED WITH INSERTION OF THE TRANSGENE; 3) PERFORM COMPARATIVE TRANSCRIPTOMIC PROFILING AND WHOLE-GENOME DNA METHYLATION PROFILING IN THE SET OF THOSE LINES; AND 4) INVESTIGATE PHENOTYPIC VARIATIONS AND POTENTIAL CONSEQUENCES IN THE LINES. THE RESULTS OF A WHOLE GENOME SEQUENCING, COMPARATIVE TRANSCRIPTOME PROFILING, DNA METHYLATION PROFILING, AND OTHER PHENOTYPING APPROACHES WILL PROVIDE FEDERAL REGULATORY AGENCIES WITH RELEVANT NEW GENOMIC AND UNINTENDED PHENOTYPIC INFORMATION OF TRANSGENIC AND GENE EDITING CROPS. THIS PROJECT ALIGNS WITH USDA BRAG PROGRAM AREA #5: OTHER RESEARCH TOPICS DESIGNED TO FURTHER THE PURPOSES OF THIS PROGRAM: COMPARISON OF THE TYPES AND FREQUENCIES OF NUCLEIC ACID CHANGES INTRODUCED INTO IMPORTANT CROP GENOMES, VIA GENETIC ENGINEERING TECHNIQUES VERSUS OTHER PLANT BREEDING TECHNIQUES.
$499,894Kansas State University · · FY2019 · National Institute of Food and Agriculture
Research Resources for Model Amphibians
$499,886Stephen Randal Voss · University Of Kentucky · R24 · FY2023 · OD