Sort
17,054 grants matching “genome editing”
CAREER: Mechanistic Investigations of Conformational Activation and Catalysis in Emerging CRISPR-Cas Systems
$650,111Giulia Palermo · University Of California-Riverside · · FY2022 · MPS
(PQ3) Cellular and Molecular Mechanisms Driving Myeloid Compartment Variation in Human Triple Negative Breast Cancer
$650,064Anna Karolina Palucka · Jackson Laboratory · R01 · FY2019 · CA
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** BIOTECHNOLOGY FOR CROP GENETIC IMPROVEMENT BECOMES INCREASINGLY IMPORTANT FOR ENHANCING AGRICULTURAL PRODUCTION. HOWEVER, WHEN INTRODUCING FOREIGN GENES INTO TARGET CROPS USING TRANSGENIC APPROACH, OR MANIPULATING ENDOGENOUS GENE EXPRESSION IN TARGET CROPS USING GENOME EDITING FOR TRAIT MODIFICATION, THE PRESENCE OF UNDESIRABLE DNAS PERMANENTLY RESIDING IN THE HOST GENOMES OF THE FINAL TRANSGENIC PRODUCTS RAISES QUESTIONS OF POTENTIAL HAZARDS OR ADVERSE EFFECTS OF THESE COMPONENTS TO THE HOST, ENVIRONMENT AND HUMAN HEALTH. IT IS THEREFORE CRITICAL TO REMOVE THESE UNDESIRABLE DNAS IN THE FINAL PRODUCTS. SITE-SPECIFIC DNA RECOMBINASES CATALYZE RECIPROCAL DNA EXCHANGE BETWEEN SPECIFIC DNA TARGET SITES AND THEREFORE CAN ALTER GENOMIC DNA SEQUENCES IN SPECIFIC WAYS PROVIDING POWERFUL TOOLS IN PLANT BIOTECHNOLOGY AND BIOSAFETY, FOR EXAMPLE THEIR USE FOR DNA EXCISION IN REMOVING UNDESIRABLE DNA TO PRODUCE CLEAN AND ENVIRONMENTALLY FRIENDLY TRANSGENICS, AND THEIR USE IN DEVELOPING GENE CONTAINMENT STRATEGIES. HOWEVER, THE OBSERVATIONS OF RECOMBINASES-MEDIATED UNEXPECTED PHENOTYPIC IMPACT ON MODEL AND CROP PLANTS RAISE VALID CONCERNS ABOUT THE POTENTIALLY UNINTENDED AND OFF-TARGET HOST PHENOTYPIC, GENOME AND EPIGENOME MODIFICATIONS BY RECOMBINASES. THE MAJOR OBJECTIVE OF THIS PROJECT IS TO INVESTIGATE HOW THE COMMONLY USED SITE-SPECIFIC RECOMBINASE GENES, CRE, FLP AND PHIC31, WHEN CONSTITUTIVELY EXPRESSED OR INDUCED IN CREEPING BENTGRASS - AN ECONOMICALLY AND ENVIRONMENTALLY IMPORTANT MONOCOT PERENNIAL GRASS SPECIES, AND IN ARABIDOPSIS - A DICOT MODEL PLANT, WOULD HAVE UNINTENDED OFF-TARGET EFFECTS TO HOST GENOMES, EPIGENOMES AND PHENOTYPES, AND THUS NEGATIVELY OR POSITIVELY AFFECT PLANT TRAITS INCLUDING DEVELOPMENT, GROWTH, AND STRESS RESPONSES AND PRESENT HAZARDS TO ENVIRONMENT. WE WILL EXAMINE WHETHER AND HOW THE RECOMBINASES-MEDIATED PHENOTYPIC CHANGES ARE ASSOCIATED WITH UNINTENDED AND OFF-TARGET MODIFICATIONS IN HOST GENE EXPRESSION AND EPIGENETIC MODIFICATIONS AT GLOBAL SCALE. DATA OBTAINED WILL ALLOW FEASIBILITY EVALUATION OF SITE-SPECIFIC RECOMBINATION SYSTEM AS A VIABLE PLATFORM FOR GENE EXCISION TO FACILITATE PLANT TRANSFORMATION AND ENABLE EXPANDED APPLICATION OF GENOME EDITING AND OTHER BIOTECHNOLOGY STRATEGIES FOR CROP PERFORMANCE AND BIOSAFETY ENHANCEMENT. THE RESEARCH WILL PROVIDE INFORMATION FOR REGULATORY AGENCIES TO ASSESS SITE-SPECIFIC RECOMBINATION SYSTEM-RELATED BIOTECHNOLOGY STRATEGIES DEVELOPED FOR TRANSGENE EXCISION AND CONTAINMENT. THE PROJECT SPECIFICALLY ADDRESSES PROGRAM AREA 5A: RESEARCH ADDRESSING PHENOTYPIC EFFECTS ASSOCIATED WITH UNINTENDED AND OFF-TARGET MODIFICATIONS IN GE ORGANISMS DEVELOPED USING GENOME EDITING TECHNOLOGY OR OTHER GENETIC ENGINEERING TECHNIQUES AND POTENTIAL HAZARDS OR ADVERSE EFFECTS (E.G., RESISTANCE) ASSOCIATED WITH THESE PHENOTYPIC EFFECTS TO THE ENVIRONMENT. THE PROJECT ALSO INDIRECTLY ADDRESSES PROGRAM AREA 1D, DEVELOPMENT OR EVALUATION OF EFFECTIVE STRATEGIES, INCLUDING MOLECULAR AND/OR GENETIC,,TO LIMIT GENE TRANSFER (GENE FLOW) OR OUTCROSSING TO SEXUALLY COMPATIBLE ORGANISMS OR TRANSFER OF GENETIC MATERIAL BETWEEN VIRUSES, INSECTS, OR MICROORGANISMS.
$650,000Clemson University · · FY2024 · National Institute of Food and Agriculture
IMPROVING WHEAT YIELD POTENTIAL TO MEET FUTURE DEMANDS FOR FOOD WHILE REDUCING LAND USE AND PROMOTING SUSTAINABLE FARMING REQUIRES CONCERTED EFFORTS OF RESEARCH AND BREEDING COMMUNITY AIMED AT 1) DISCOVERING GENETIC VARIANTS CONTROLLING PHYSIOLOGICAL AND DEVELOPMENTAL PROCESSES THAT CONTRIBUTE TO TRAITS OF AGRONOMIC IMPORTANCE, ESPECIALLY PRODUCTIVITY AND NUTRITIONAL VALUE TRAITS, 2) EVALUATING THE PHENOTYPIC EFFECTS OF INDIVIDUAL AND STACKED BENEFICIAL VARIANTS IN ADAPTED GERMPLASM UNDER REALISTIC AGRICULTURAL SETTINGS, AND THEN 3) USING THIS KNOWLEDGE TO REDESIGN WHEAT PLANT BY STRATEGICALLY COMBINING THOSE ALLELES WHOSE INTERACTION GREATLY ENHANCES TRAIT EXPRESSION. WHILE PROGRESS WAS MADE TOWARDS IDENTIFYING THE GENETIC BASIS OF MANY AGRONOMIC TRAITS, WE STILL NEED TO EXPAND GENETIC DIVERSITY ACCESSIBLE FOR BREEDING BY EITHER INTRODUCING NEW DIVERSITY FROM THE ANCESTRAL POPULATIONS OF WILD RELATIVES OR LANDRACES, OR BY CREATING NOVEL VARIANTS BY MUTAGENESIS OR GENE EDITING. WE STILL HAVE LIMITED UNDERSTANDING OF HOW DISCOVERED GENES AND THEIR ALLELES WILL PERFORM IN DIVERSE GENETIC BACKGROUNDS OR ENVIRONMENTS, OR HOW TRAITS AFFECTING DIFFERENT ASPECTS OF WHEAT BIOLOGY WILL INTERACT WITH EACH OTHER ONCE COMBINED. TO ADDRESS THESE CHALLENGES, URGENT INTEGRATION OF INNOVATIVE TECHNOLOGIES AND BREEDING STRATEGIES INTO THE TRANSLATIONAL ACTIVITIES IS REQUIRED.OVER THE LAST DECADE, BY THE EFFORTS OF NATIONAL AND INTERNATIONAL WHEAT RESEARCH PROGRAMS, THE GENETIC BASIS OF MANY AGRONOMIC TRAITS HAS BEEN ESTABLISHED. THE RELEASE OF THE ANNOTATED WHEAT GENOME SEQUENCE AND DEVELOPMENT OF COMPARATIVE GENOMICS TOOLS AND RESOURCES PROVIDED A POWERFUL FRAMEWORK FOR EXTRAPOLATING GENE MAPPING INFORMATION FROM OTHER CROPS INTO WHEAT. THESE DISCOVERIES NOW PROVIDE UNIQUE OPPORTUNITY TO REDESIGN BIOLOGICAL PATHWAYS UNDERLYING MAJOR AGRONOMIC TRAITS IN WHEAT BY INTRODUCING THE FAVOURABLE ALLELES OF CAUSAL GENES INTO THE BREEDING PIPELINES.MANY STUDIES DEMONSTRATED THAT THE CRISPR-CAS SYSTEM CAN TAKE FULL ADVANTAGE OF THESE NEW GENOMIC RESOURCES AND FACILITATE THE CHARACTERIZATION AND DEPLOYMENT OF THE NOVEL GENE VARIANTS. OUR PROJECT WILL ESTABLISH PLANT BREEDING PARTNERSHIP INCLUDING KANSAS STATE UNIVERSITY (KSU) AND THE UNIVERSITY OF SASKATCHEWAN (CANADA) WITH THE AIM TO INTEGRATE THE CRISPR-CAS-BASED TECHNOLOGY INTO THE WHEAT PRE-BREEDING PIPELINES AND IMPROVE WHEAT PRODUCTIVITY AND NUTRITIONAL QUALITY TRAITS IN ADAPTED GERMPLASM. THIS PROJECT WILL BUILD ON THE RESOURCES GENERATED IN THE ON-GOING GENE EDITING PROJECTS CONDUCTED BY THE PROJECT DIRECTORS AND COLLABORATORS. THE PROJECT ACTIVITIES WILL BE INTEGRATED WITH THE WHEAT CAP AND IWYP PROJECTS, AND THE FUTURE NIFA IWYP WINTER WHEAT BREEDING INNOVATION HUB IN MANHATTAN (KS).HERE, WE WILL CREATE VARIATION IN THE PROTEIN CODING OR REGULATORY REGIONS OF GENES THAT CAN INFLUENCE PLANT GROWTH, SPIKE AND GRAIN DEVELOPMENT, AND NUTRIENT ACCUMULATION IN GRAIN. WE WILL MAKE USE OF CRISPR-EDITED WHEAT LINES GENERATED BY OUR TEAM IN A PREVIOUS PROJECT WITH MUTATIONS IN THE GENES AFFECTING GRAIN SIZE AND WEIGHT, AND NUMBER OF GRAINS PER HEAD.WE WILL TEST A NEW STRATEGY TO CREATE NOVEL PHENOTYPIC VARIATION BY MUTATING THE REGULATORY REGIONS OF GENES CONTROLLING NITROGEN UPTAKE, CARBON FIXATION, GROWTH AND NUTRIENT REMOBILIZATION. CURRENTLY, WE HAVE LIMITED UNDERSTANDING OF THE RANGE OF POSSIBLE QUANTITATIVE VARIATION FOR THESE TRAITS THAT CAN BE GENERATED BY EDITING THE REGULATORY REGIONS OF GENES. IN THIS PROJECT, WE WILL INVESTIGATE PHENOTYPES PRODUCED BY THE CRISPR-CAS9-EDITED PROMOTER VARIANTS AND ASSESS THEIR UTILITY FOR WHEAT IMPROVEMENT. BY COMBINING AND TESTING DIFFERENT REGULATORY VARIANTS OF GENES SHOWING DIFFERENT LEVELS OF EXPRESSION, WE WILL IDENTIFY OPTIMAL COMBINATIONS OF VARIANTS SUPPORTING EFFECTIVE NITROGEN UPTAKE AND PLANT GROWTH.THE IDENTIFICATION AND ASSEMBLY OF POSITIVELY INTERACTING COMBINATIONS OF GENES AFFECTING WHEAT PRODUCTIVITY TRAITS HAS A POTENTIAL TO SUBSTANTIALLY INCREASE YIELD. ONE OF THE PRE-REQUISITES FOR THE IMPLEMENTATION OF THIS STRATEGY IS THE IDENTIFICATION OF ALLELES THAT DO NOT SHOW NEGATIVE INTERACTION. BY TRANSFERRING THE CRISPR-EDITED GENE VARIANTS INTO THE ADAPTED GERMPLASM ALREADY SELECTED FOR OTHER BENEFICIAL AND COMPLEMENTARY TRAITS (E.G. HIGH BIOMASS, IMPROVED PLANT ARCHITECTURE, ETC.), THIS PROJECT WILL INVESTIGATE THE UTILITY OF QUANTITATIVE TRAIT VARIATION INDUCED BY GENE EDITING FOR WHEAT IMPROVEMENT, AND IDENTIFY THE COMBINATIONS OF GERMPLASM AND CRISPR-CAS INDUCED ALLELES CAPABLE OF SUPPRESSING NEGATIVE INTERACTION AMONG THE WHEAT PRODUCTION TRAITS.WITH GENE EDITING BECOMING ONE OF THE VALUABLE ASSETS IN THE BREEDER'S CROP IMPROVEMENT TOOLBOX, TRAINING OPPORTUNITIES FOR GRADUATE STUDENTS AND POSTDOCTORAL RESEARCHERS THAT INTEGRATE GENE EDITING SYSTEM WITH BREEDING METHODOLOGIES, BIOINFORMATICS, COMPARATIVE GENOMICS, AND MOLECULAR GENETICS ARE REQUIRED.IN OUR PROJECT, WE WILL DEVELOP EDUCATIONAL MODULES FOR POSTDOCTORAL RESEARCHERS AND PHD STUDENTS TO PROVIDE TRAINING IN APPLICATIONS OF GENE EDITING TECHNOLOGY FOR CROP IMPROVEMENT, REGULATORY ASPECTS OF CROP BIOTECHNOLOGY AND SCIENCE COMMUNICATION. THESE TRAINING IS INTENDED TO PREPARE THE NEW GENERATION OF CROP SCIENTISTS TO FACE THE CHALLENGES OF COMMUNICATING THEIR DISCOVERIES TO THE PUBLIC, CONSUMER GROUPS AND POLICYMAKERS TO ENSURE THAT THE SCIENCE-BASED POLICIES PREVAIL.
$650,000Kansas State University · · FY2020 · 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.** EXCESSIVE FAT ACCRETION CAUSES DECREASED FEED EFFICIENCY, LEADING TO ECONOMIC LOSSES IN THE POULTRY INDUSTRY. DISCOVERY OF NUTRITIONAL, HORMONAL, AND GENETIC FACTORS WHICH INFLUENCE ADIPOSE DEVELOPMENT WILL PROVIDE THE NECESSARY FOUNDATIONAL EVIDENCE TO DEVELOP STRATEGIES FOR IMPROVING PRODUCTION EFFICIENCY. VITAMIN A (AS RETINOL) AND ITS METABOLITE, RETINOIC ACID (RA), REGULATES FAT ACCRETION. MOST IN VIVO STUDIES WITH DIETARY CHALLENGES OR INJECTION OF RA SHOWED A DECREASED FAT ACCRETION RATE BY ACTIVATING BREAKDOWN OF STORED FAT IN MATURE ADIPOCYTES OF ADULT ANIMALS. HOWEVER, OUR PRELIMINARY DATA SHOWED PROMOTION OF PREADIPOCYTE DIFFERENTIATION IN VITRO AND INCREASED FAT ACCRETION DURING EMBRYO DEVELOPMENT BY RA. WE DISCOVERED AN ADIPOSE-SPECIFIC GENE, RETINOL BINDING PROTEIN 7 (RBP7), THAT INCREASES CELLULAR RA CONCENTRATION AND PROMOTES ADIPOCYTE DIFFERENTIATION IN VITRO. THEREFORE, IT IS HYPOTHESIZED THAT RA HAS DUAL FUNCTIONS IN POULTRY: 1) RA PROMOTES ADIPOCYTE DIFFERENTIATIONDURING EMBRYONIC AND EARLY POST-HATCH AGES, AND 2) RA ENHANCES BREAKDOWN STORED FAT IN MATURE ADIPOCYTES, DECREASING FAT ACCRETION IN ADOLESCENT AND MATURE BIRDS. TO TEST OUR HYPOTHESIS, WE WILL PURSUE TWO OBJECTIVES; 1) DEFINE THE CONTRIBUTION OF THE RBP7 GENE TO FAT ACCRETION IN QUAIL VIA A TARGETED GENOME-EDITION IN RBP7 GENE, AND 2) DETERMINE TO WHAT EXTENT CONCENTRATIONS OF RA IN EGGS FOR EMBRYOS AND DIETS FOR CHICKS CHANGE FAT ACCRETION IN BROILERS. OUTCOMES FROM THE PROPOSED STUDIES WILL LEAD TO ESTABLISHING RBP7 AS A GENETIC MARKER FOR SELECTION OF POULTRY BREEDERS WITH LESS FAT AND DEVELOPING DIETARY STRATEGIES WITH RA TO REDUCE ADIPOSE GROWTH AND INCREASE FEED EFFICIENCY.
$650,000Ohio State University, The · · FY2022 · 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.** MAJOR PLANT OIL CROPS PRODUCE TRIACYLGLYCEROLS (TAG, E.G. OIL) COMPOSED OF PREDOMINANTLY FIVE COMMON FATTY ACIDS. HOWEVER, THE PLANT KINGDOM PRODUCES MORE THAN 450 UNUSUAL FATTY ACIDS THAT CAN BE USEFUL AS CHEMICAL FEED STOCKS IN A WIDE RANGE OF INDUSTRIES. FOR EXAMPLE, CASTOR OIL (PRODUCED MOSTLY IN INDIA) IS WORTH OVER $1 BILLION USD PER YEAR AND THE HYDROXY FATTY ACIDS (HFA) CONTAINED IN THE OIL ARE USED FOR PHARMACEUTICALS, COSMETICS, PLASTICS, BIODEGRADABLE POLYESTERS, AND BIOFUELS. THE US IS A MAJOR IMPORTER OF CASTOR OIL FOR THE OLEOCHEMICAL INDUSTRY. RESEARCH TO ENGINEER HFA PRODUCTION INTO A CURRENT DOMESTIC OILSEED CROP HAS HAD VERY LIMITED SUCCESS. HOWEVER, PHYSARIA FENDLERI IS A BURGEONING OILSEED CROP NATIVE TO THE US THAT PRODUCES HFA SIMILAR TO CASTOR. OUR RECENT RESEARCH IN P. FENDLERI INDICATES IT UTILIZES A NOVEL TAG REMODELING BIOSYNTHETIC PATHWAY TO EFFICIENTLY ACCUMULATE HFA AND OVERCOME THE METABOLIC BOTTLENECKS THAT ARE PRESENT WHEN HFA PRODUCTION IS ENGINEERED INTO OTHER CROP SPECIES. THIS PROPOSAL WILL: (1) UTILIZE A NEWLY DEVELOPED FUNCTIONAL GENOMICS APPROACH IN P. FENDLERI TO ELUCIDATE THE EFFICIENT MECHANISMS OF HFA ACCUMULATION, THAT COULD BE USED FOR ENGINEERING DESIGNER OIL COMPOSITIONS INTO CROP PLANTS; (2) UTILIZE GENE EDITING TO ENHANCE P. FENDLERI AS A DOMESTIC SOURCE OF HFA BY INCREASING SEED OIL, HFA CONTENT, AND TOTAL SEED YIELDS; (3) EVALUATE THE USE OF P. FENDLERI (AND ITS NOVEL TAG REMODELING MECHANISMS) AS A DOMESTIC PLATFORM CROP FOR PRODUCTION OF VARIOUS INDUSTRIALLY VALUABLE FATTY ACIDS.
$650,000Washington State University · · FY2023 · 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.** NATURAL PRODUCTS OR PHYTOCHEMICALS MADE BY PLANTS HAVE VALUABLE FUNCTIONS AS FOOD INGREDIENTS AND PHARMACEUTICALS, AND IN INDUSTRIAL PRODUCTION. THIS PROJECT INVESTIGATES A SPECIAL CLASS OF PLANT NATURAL PRODUCTS THAT OCCURS IN CARROTS AND IN RELATED AROMATIC HERBS SUCH AS FENNEL AND PARSLEY AS WELL AS IN SPICES SUCH AS NUTMEG. THESE PHYTOCHEMICALS, ALSO KNOWN AS PHENYLPROPENES, HAVE BEEN VALUED BY HUMANS FOR CENTURIES FOR THEIR FLAVORING, ANTIMICROBIAL, INSECTICIDAL, AND MEDICINAL ATTRIBUTES BUT ARE ALSO RECOGNIZED FOR THEIR TOXIC AND PSYCHOACTIVE EFFECTS. THE PROPOSED RESEARCH WILL UNRAVEL THE FORMATION OF THESE COMPOUNDS AND UNLOCK THEIR VAST POTENTIAL FOR AGRICULTURAL, PHARMACEUTICAL, AND BIOTECHNOLOGICAL APPLICATIONS WHILE PROVIDING GENETIC INFORMATION TO CONTROL THEIR LEVELS IN SPICES AND FOOD CROPS.THE RESEARCH PROJECT WILL USE GENOMIC, BIOCHEMICAL, AND ANALYTICAL TECHNIQUES TO IDENTIFY THE GENES INVOLVED IN THE BIOSYNTHESIS OF PHENYLPROPENE NATURAL PRODUCTS IN CARROT AND RELATED HERBS AS WELL AS IN NUTMEG. GENE EDITING WILL BE APPLIED TO MINIMIZE BITTERNESS CAUSED BY THE PHENYLPROPENE COMPOUNDS IN CARROT ROOTS, AND ENGINEERING APPROACHES WILL BE EMPLOYED TO ENHANCE THE FORMATION OF THE COMPOUNDS IN CARROT LEAVES AS NATURAL DEFENSES AGAINST SEVERE CARROT PESTS. OUTCOMES OF THE PROJECT WILL ALLOW CROP IMPROVEMENT BY TARGETED BREEDING OF CARROT AND BIOTECHNOLOGICAL TRANSFER TO RELATED CROPS AND SPICES TO BETTER CONTROL PHENYLPROPENE LEVELS. THE WORK WILL FURTHER SET THE STAGE FOR THE SUSTAINABLE BIOTECHNOLOGICAL PRODUCTION OF THESE COMPOUNDS IN THE DEVELOPMENT OF PHARMACEUTICALS AND AS CRITICAL CHEMICAL STARTERS FOR HIGH VALUE INDUSTRIAL PRODUCTS.
$650,000Virginia Polytechnic Institute & State University · · 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.** POTATO (SOLANUM TUBEROSUM) IS THE THIRD MOST-CONSUMED FOOD CROP IN THE WORLD GROWN IN ROUGHLY 130 COUNTRIES, 95 OF WHICH ARE DEVELOPING COUNTRIES. POTATO IS CONSIDERED A FOOD SECURITY CROP FOR DEVELOPING NATIONS, IN WHICH POTATO PRODUCTION HAS RAMPED UP SUBSTANTIALLY OVER THE PAST 30 YEARS. THE US REMAINS THE FOURTH LARGEST PRODUCER OF POTATOES IN THE WORLD. POTATO IS A TOP FIVE COMMODITY CROP IN THE PDS' HOME STATE OF NEVADA. POTATO HAS AN ANNUAL VALUE OF $4.2 BILLION IN THE USA. UP TO 33% OF THE US POTATO TUBER CROP IS LOST DUE TO POSTHARVEST ISSUES LIKE WOUNDING, BRUISING, AND PATHOGEN ATTACK. THESE LOSSES CAN REACH AS HIGH AS 50% IN DEVELOPING NATIONS DUE TO FACTORS SUCH AS LACK OF PROPER STORAGE CONDITIONS. THE ECONOMIC IMPORTANCE OF POTATO EXTENDS BEYOND THE VALUE OF THE HARVESTED CROP. THE GLOBAL POTATO PROCESSING MARKET IS CURRENTLY VALUED AT $27.4 BILLION AND IS EXPECTED TO GROW TO $35.4 BILLION BY 2026.IT IS WELL KNOWN THAT WOUND HEALING AND DEPOSITION OF THE CORKY MATERIAL SUBERIN IN WOUND SITES IS OF CRITICAL IMPORTANCE TO THE THE POST-HARVEST STORAGE LIFE OF POTATOES. WOUND SUBERIN DEPOSITION CAPACITY AND STORAGE LIFE ARE POSITIVELY CORRELATED. THAT IS TO SAY, POTATO CULTIVARS WITH BETTER WOUND SUBERIN DEPOSITION CAPACITY TEND TO HAVE LONGER STORAGE LIFE. EFFORTS TO IMPROVE WOUND HEALING CAPACITY OF THE USA'S NUMBER ONE VEGETABLE CROP MUST BE INFORMED BY UNDERSTANDING THE FUNDAMENTAL PROCESSES THAT GOVEN WOUND HEALING. THIS CAN BE ACCOMPLISHED BY UNDERSTANDING THE GENES AND SIGNALING PROCESSES THAT GOVERN WOUND SUBERIN DEPOSITION. THISRESEARCH PROJECT AIMS TO DO EXACTLY THAT, TO PROVIDE AN IN-DEPTH UNDERSTANDING OF THE GENETIC AND SIGNALING FACTORS THAT REGULATE WOUND HEALING IN A CROP SPECIES IMPORTANT FORNATIONAL AND GLOBAL FOOD SECURITY, POTATO.TO ACCOMPLISH THIS, CUTTING-EDGE GENOMICS AND GENOME EDITING TECHNIQUES, SUCH AS CRISPR AND HIGH-THROUGHPUT DNA/RNA SEQUENCINGWILL BE EMPLOYED. THROUGH THIS WORK, POTATO GERMPLASM WITH ALTERED WOUND SUBERIN DEPOSITION CAPACITY WILL BE GENERATED. THE GERMPLASM AND INFORMATION GENERATED THROUGH THIS RESEARCH WILL PROVIDE A VALUABLE RESOURCE FOR PLANT BREEDING EFFORTS AIMED AT REDUCING POST-HARVEST POTATO TUBER LOSSESTHAT WILL TRANSLATABLE TO OTHER CROPS THAT UNDERGO LONG-TERM STORAGE (E.G. SWEET POTATO, RUTABAGA, CARROT, ETC.).
$650,000Board Of Regents Of Nevada System Of Higher Education · · FY2024 · National Institute of Food and Agriculture
RUI: DNA replication in Chlamydomonas reinhardtii
$650,000Amy Ikui · Cuny Brooklyn College · · FY2025 · BIO
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** CHICKEN EMBRYONIC STEM CELLS (ESC) AND PRIMORDIAL GERM CELLS (PGC) ARE PRECURSORS OF SPERM CELLS AND OVA. THEY ARE ESSENTIAL IN GENOME EDITING, PRECISION BREEDING, CELLULAR ENGINEERING, AND MECHANICAL RESEARCH DURING CHICKEN GROWTH DEVELOPMENT AND REPRODUCTION. HOWEVER, OUR UNDERSTANDING OF THE REGULATIONS REGARDING STEM CELLS IN SEX CONTROL IS STILL LIMITED. CHARACTERIZATION OF EPIGENETIC REGULATION WILL PROVIDE A COMPREHENSIVE VIEW OF THE MOLECULAR MECHANISMS THAT GOVERN SELF-RENEWAL AND LINEAGE COMMITMENT. THIS PROJECT HYPOTHESIZES THAT REGULATORY ELEMENTS EPIGENETICALLY DETERMINE THE PROLIFERATION AND TRANSITION OF CHICKEN ESC TO PGC. THE PROJECT AIMS TO PROVIDE DETAILED FUNCTIONAL REGULATORY ELEMENTS, NCRNAS, CHROMATIN STATUS, AND CRUCIAL MOLECULAR PATHWAYS OF THE CHICKEN EMBRYONIC GERM CELLS. THE VALUABLE INFORMATION WILL HELP US ASCERTAIN THE MECHANISMS OF THE DIFFERENTIATION AND PROLIFERATION OF CHICKEN GERM CELLS. WITH A DEEP UNDERSTANDING OF THE FORMATION OF THE PGC MECHANISMS, WE WILL IMPROVE THE EFFICIENCY OF ESC TRANSITION TO PGCS FOR PRESERVING, REGENERATING, CLONING, AND GENOME EDITING OF POULTRY, THUS ENHANCING POULTRY GENETICS AND BREEDING. WE FORESEE THAT THE PROGRESS MAY FURTHER SHORTEN GENERATION INTERVALS AND IMPROVE CHICKEN GENOME EDITING AND COMPARATIVE GENOMICS, EPIGENETICS, AND SEX CONTROL, THUS GENERATING ENORMOUS BENEFITS FOR POULTRY STAKEHOLDERS. LASTLY, THE DATA FROM THE PROJECT ARE SUBSTANTIALLY COMPLEMENTARY TO THE ANNOTATION OF THE CHICKEN GENOME. THE PROJECT WILL IMPROVE CHICKEN GROWTH AND DEVELOPMENT, GENOME ANNOTATION, AND REPRODUCTIVE EFFICIENCY, WHICH ARE OF SIGNIFICANT INTEREST TO POULTRY SCIENCE RESEARCHERS AND STAKEHOLDERS.
$650,000University Of Maryland, College Park · · FY2023 · National Institute of Food and Agriculture
CRISPR Capture, Destroy, and Counter-Attack Mechanisms
$650,000Michael P Terns · University Of Georgia · R35 · FY2021 · GM
THE PROPOSED RESEARCH ALIGNS WITH PROGRAM AREA #5: OTHER RESEARCH TOPICS DESIGNED TO SUPPORT THE PURPOSES OF THE BRAG PROGRAM. OUR PROPOSAL AIMS AT TESTING THE EFFICACY AND SPECIFICITY OF MULTIPLEX MUTAGENESIS IN CIS-REGULATORY REGIONS USING GENOME EDITING TO ENGINEER BROAD AND DURABLE DISEASE RESISTANCE AGAINST TWO FUNGAL PATHOGENS IN THE VEGETABLE CROP TOMATO. TO ACHIEVE THIS, WE WILL 1) EVALUATE THE EFFICIENCY OF GENOME EDITING AT INDUCING MULTIPLE TARGETED MUTATIONS IN AT LEAST FOUR SUSCEPTIBILITY GENES, 2) CHARACTERIZE TRAIT EFFICACY AND POTENTIAL PLEIOTROPIC EFFECTS IN AGRONOMIC PERFORMANCE AND 3) DETERMINE POTENTIAL OFF-TARGETS AND OTHER COMPLEX STRUCTURAL VARIATION THAT COULD ORIGINATE FROM MULTIPLEX GENOME EDITING. OUR RESULTS WILL PROVIDE AN EXTENSIVE DATASET TO EVALUATE THE EFFICACY AND SPECIFICITY OF MORE COMPLEX GENOME EDITING APPROACHES IN THE VEGETABLE CROP TOMATO. PHENOTYPIC AND GENOMIC DATA WILL BE USED FOR DETERMINING WHETHER MULTIPLEX EDITING IS A VIABLE OPTION TO DEPLOY BROAD AND DURABLE DISEASE RESISTANCE AND TO ASSESS ANY UNINTENDED OFF-TARGET AND PLEIOTROPIC EFFECTS THAT COULD AFFECT AGRONOMIC PERFORMANCE. THE DATA AND RESULTS GENERATED MAY BE USED TO DETERMINE INTENDED OR UNINTENDED EFFECTS BEYOND THOSE THAT MAY BE OBTAINED BY OTHER TECHNOLOGIES.
$649,999University Of Maryland, College Park · · FY2025 · National Institute of Food and Agriculture
MULTIPLEX GENOME EDITING IS A POWERFUL TOOL FOR CROP IMPROVEMENT, BUT IT ALSO RAISES CONCERNS ABOUT UNINTENDED CHROMOSOME REARRANGEMENTS AND CHANGES IN GENE EXPRESSION. THESE UNINTENDED EFFECTS MAY POSE CHALLENGES FOR PLANT BREEDERS, REGULATORY AGENCIES, AND AGRICULTURAL STAKEHOLDERS. THIS PROJECT WILL USE TOMATO AS A MODEL SYSTEM TO SYSTEMATICALLY INVESTIGATE THE UNINTENDED CONSEQUENCES OF MULTIPLEX GENOME EDITING AT THE CHROMOSOMAL, GENE EXPRESSION, AND PHENOTYPIC LEVELS. BY COMPARING MULTIPLEX-EDITED PLANTS WITH GENETICALLY TRANSFORMED PLANTS, THE STUDY WILL PROVIDE VALUABLE INSIGHTS TO GUIDE THE SAFE AND EFFECTIVE APPLICATION OF GENOME EDITING. THE ULTIMATE GOAL IS TO GENERATE SCIENCE-BASED INFORMATION THAT SUPPORTS RESPONSIBLE USE OF GENOME EDITING IN AGRICULTURE, STRENGTHENS REGULATORY DECISION-MAKING, AND FOSTERS PUBLIC CONFIDENCE.
$649,998University Of Connecticut · · FY2025 · 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.** OUR RESEARCH AIMS TO DEVELOP A NEW METHOD FOR PRODUCING HYBRID SEEDS IN WHEAT AND BARLEY, WHICH COULD SIGNIFICANTLY INCREASE YIELDS OF THESE IMPORTANT CEREAL CROPS. WE HAVE PREVIOUSLY DISCOVERED A GENETIC PATHWAY IN DURUM WHEAT THAT CAN INDUCE CONDITIONAL MALE STERILITY - THE INABILITY TO SELF-POLLINATE - WHEN DISRUPTED. THIS STERILITY CAN BE TRIGGERED BY ENVIRONMENTAL FACTORS LIKE DAY LENGTH OR TEMPERATURE. IN THIS PROJECT, WE WILL APPLY ADVANCED GENE EDITING (CRISPR) AND PLANT TRANSFORMATION TECHNIQUES TO DISABLE THE SAME KEY GENE IN DIVERSE VARIETIES OF BREAD WHEAT AND BARLEY. THIS SHOULD RENDER THE PLANTS MALE-STERILE UNDER CERTAIN ENVIRONMENTAL CONDITIONS, WHILE ALLOWING NORMAL FERTILITY UNDER PERMISSIVE CONDITIONS. WE WILL GROW THE GENETICALLY MODIFIED WHEAT AND BARLEY PLANTS AND EVALUATE THEIR MALE FERTILITY ACROSS DIFFERENT TEMPERATURE AND DAY LENGTH REGIMES. THIS WILL ALLOW US TO OPTIMIZE THE ENVIRONMENTAL TRIGGERS FOR SWITCHING BETWEEN MALE-STERILE AND FERTILE STATES. IN-DEPTH ANALYSES WILL EXAMINE THE DEVELOPMENTAL IMPACTS IN THE PLANT'S ANTHERS (POLLEN-PRODUCING STRUCTURES) RESULTING FROM THIS GENETIC DISRUPTION. THE RESEARCH TEAM HAS EXPERTISE SPANNING SMALL RNAS, PLANT GENOMICS, REPRODUCTIVE BIOLOGY, ANTHER DEVELOPMENT, AND HYBRID SEED PRODUCTION METHODS. PRELIMINARY DATA SUGGESTS THIS INNOVATIVE APPROACH IS FEASIBLE ACROSS DIVERSE CROP VARIETIES. IF SUCCESSFUL, THIS ENVIRONMENTALLY-CONTROLLED MALE STERILITY SYSTEM COULD ENABLE WIDESPREAD HYBRID SEED PRODUCTION FOR WHEAT AND BARLEY. THIS COULD BOOST YIELDS BY AT LEAST 15% - REPRESENTING MILLIONS OF TONS OF ADDITIONAL GRAIN PRODUCED USING THE SAME AGRICULTURAL INPUTS AND LAND AREA. IN SUMMARY, WE AIM TO LEVERAGE A NEWLY DISCOVERED GENETIC PATHWAY TO DEVELOP A ROBUST TECHNOLOGY FOR HYBRID WHEAT AND BARLEY PRODUCTION, UNLOCKING SIGNIFICANT POTENTIAL YIELD INCREASES FOR THESE GLOBALLY IMPORTANT CEREAL CROPS.
$649,976University Of California, Davis · · 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 PROPOSED PROJECT ADDRESSES THE PROGRAM AREA PLANT BREEDING FOR AGRICULTURAL PRODUCTION (A1141). THE LONG-TERM GOAL OF THIS RESEARCH IS TO REMOVE IMMUNOGENIC-GLUTEN PROTEINS, NOT WHEAT, FROM THE DIET. THIS GOAL WILL BE ACHIEVED BY DEVELOPING REDUCED IMMUNOGENICITY, LYSINE-RICH WHEAT GENOTYPES USING CONVENTIONAL AND GENOME-EDITING METHODS. THESE REDUCED-IMMUNOGENICITY GENOTYPES OFFER AN EASY-TO-INTEGRATE SOLUTION IN THE CURRENT PRODUCTION, PROCESSING, AND DISTRIBUTION SYSTEMS, HENCE OFFERING AN AFFORDABLE SOLUTION TO ALL IRRESPECTIVE OF THEIR SOCIOECONOMIC STRATA. THE FOLLOWING SPECIFIC OBJECTIVES WILL BE UNDERTAKEN TO ACHIEVE THE PROPOSED GOAL. 1) DEVELOP NON-IMMUNOGENIC WHEAT GENOTYPES BY STACKING NULL-MUTANTS AT WHEAT GLIADIN AND GLUTENIN LOCI. THIS OBJECTIVE WILL BE ACHIEVED BY THE GENETIC CROSSING OF REDUCED-GLUTEN MUTANTS OR USING A NOVEL COMBINATION OF MULTI-GENE EDITING AND NANOPARTICLE-BASED GENE DELIVERY METHOD. 2) EVALUATE SELECTED REDUCED-IMMUNOGENICITY WHEAT GENOTYPES FOR SUITABILITY FOR HUMAN CONSUMPTION. THIS OBJECTIVE WILL BE ACHIEVED BY A DETAILED CHARACTERIZATION OF WHEAT GENOTYPES WITH STACKED GLIADIN AND GLUTENIN NULL MUTANTS FOR THEIR BIOCHEMICAL AND IMMUNOLOGICAL PROPERTIES USING ELECTROPHORESIS, LIQUID CHROMATOGRAPHY, MASS SPECTROMETRY, AND IMMUNOLOGICAL ASSAYS (ELISA AND T-CELL). SELECTED LINES WILL BE ACCESSED FOR END-USE PERFORMANCE. 3) ASSESS THE SOCIAL AND COMMERCIAL ACCEPTANCE OF THE REDUCED-IMMUNOGENICITY WHEAT LINES. THE OBJECTIVE WILL BE ACHIEVED BY SURVEYING CONSUMERS' OPINIONS, INCLUDING CELIAC PATIENTS, WHEAT PRODUCERS, MILLERS, AND BAKERS, ON USING GENOME EDITING TO DEVELOP REDUCED-IMMUNOGENICITY, HIGH-LYSINE WHEAT LINES. THESE INTERACTIONS WILL ALLOW RESEARCHERS TO ENHANCE THEIR UNDERSTANDING OF THE PUBLIC PERCEPTION OF THE PROPOSED SOLUTIONS AND CONSIDER THIS INFORMATION TO READJUST THE RESEARCH BASED ON PUBLIC OPINION.
$649,942Clemson University · · FY2023 · National Institute of Food and Agriculture
Regulation of Craniofacial Development by ALX Transcription Factors
$649,936Rulang Jiang · Cincinnati Childrens Hosp Med Ctr · R01 · FY2024 · DE
Enhancements to the GMOD Suite of Genome Annotation and Visualization Tools
$649,922Ian H Holmes · University Of California Berkeley · R01 · FY2025 · HG
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** ADVANCES IN BIOLOGY ARE ENABLING MORE EFFICIENT GENETIC TRANSFORMATION AND EDITING, INCLUDING FOR BIOSAFETY-PROMOTING TRAITS SUCH AS FOR GENETIC CONTAINMENT. MANY ASEXUALLY PROPAGATED SPECIES, SUCH AS THE FOREST TREES WE PROPOSE FOR STUDY, ARE NOTABLY RECALCITRANT TO TRANSFORMATION YET IN NEED OF BIOSAFETY-PROMOTING TRANSGENES OR EDITS DUE TO THEIR POTENTIAL LARGE ECOLOGICAL IMPACTS AND PROPENSITY FOR LONG DISTANCE GENE FLOW. HOWEVER, THE GENES EMPLOYED (SUCH AS CRISPR/CAS9) OFTEN NEED TO BE EXCISED (REMOVED) TO FACILITATE REGULATORY APPROVAL OR ENSURE PLANT HEALTH--PARTICULARLY IN THESE SPECIES FOR WHICH SEXUAL SEGREGATION IS DIFFICULT OR IMPOSSIBLE. THE MOST COMMON TOOLS FOR EXCISION ARE THE CRE AND FLP RECOMBINASES, HOWEVER, THEIR ACTIVITY IS CONSTRAINED BY TARGET-SITE DNA METHYLATION IN PLANTS, MAKING THEIR USE INEFFICIENT. VARIOUS MEANS FOR DEMETHYLATION ARE KNOWN TO ENHANCE EFFICIENCY, BUT HAVE NOT BEEN COMPARED OR OPTIMIZED, NOR HAVE THEIR OFF-TARGET IMPACTS EXAMINED AT THE LOCUS, GENOME, OR PHENOTYPIC LEVELS. USING TOBACCO, ARABIDOPSIS, AND POPLAR AS STUDY SYSTEMS, WE WILL: 1) DEVELOP NOVEL RECOMBINASE TARGET SITES THAT ARE DEVOID OF POTENTIALLY METHYLATED CYTOSINES BUT ARE ACTIVE IN SUPPORTING EXCISION; 2) TEST A VARIETY OF CONSTITUTIVE, INDUCIBLE, AND SITE-SPECIFIC METHYLATION INHIBITORS FOR ENHANCEMENT OF TRANSGENE EXCISION; AND 3) EXAMINE LOCAL, GENOME-SCALE AND PHENOTYPIC IMPACTS OF THE MOST EFFECTIVE METHYLATION CONTROL SYSTEMS. THIS WORK WILL HELP ENHANCE GENOME TRANSFORMATION AND ENGINEERING TOOLS RELEVANT TO BIOSAFETY TECHNOLOGY APPLICATIONS AND INFORM REGULATORS OF THE DEGREE TO WHICH THEY SHOULD BE CONCERNED WITH OFF-TARGET IMPACTS WHEN RECOMBINASES ARE USED FOR GENOME MODIFICATION.
$649,916Oregon State University · · FY2023 · National Institute of Food and Agriculture
Development and Support of the Pathway Tools Software
$649,906Peter D Karp · Sri International · R01 · FY2010 · GM
Systems Control of Normal Aging and Alzheimer's Disease
$649,874Catherine Cook Kaczorowski · Jackson Laboratory · R01 · FY2017 · AG
**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS PROJECT ADDRESSES REGIONAL AND NATIONAL AGRICULTURAL NEEDS AND OPPORTUNITIES BY DEVELOPING GERMPLASM AND GENOMIC RESOURCES IN SUPPORT OF MOLECULAR BREEDING INITIATIVES IN QUINOA (CHENOPODIUM QUINOA), A HIGHLY NUTRITIOUS, HIGH VALUE PSEUDOCEREAL CROP. CURRENTLY AVAILABLE QUINOA VARIETIES ARE NOT WELL-ADAPTED FOR PROFITABLE CULTIVATION IN MANY REGIONS OF THE UNITED STATES, INCLUDING BUT NOT LIMITED TO THE NORTHEAST AND OTHER REGIONS OF HIGH HUMIDITY. HOWEVER, THE EXISTENCE AND SUCCESS OF WILD, WEEDY RELATIVES OF QUINOA IN THESE SAME GEOGRAPHIC REGIONS INDICATES THE POTENTIAL OF QUINOA TO RESPOND TO MODERN BREEDING PRACTICES AIMED AT DEVELOPING LOCALLY ADAPTED COMMERCIAL VARIETIES. THE PROJECT APPROACH RECOGNIZES THE GENETIC COMPLEXITY OF QUINOA, WHICH STEMS FROM ITS HYBRID ORIGIN AND POLYPLOID GENOMIC CONSTITUTION. SPECIFICALLY, THE QUINOA GENOME CONSISTS OF FOUR SETS OF CHROMOSOMES (ALLOTETRAPLOIDY), RATHER THAN THE MORE USUAL TWO SETS (DIPLOIDY), WHEREBY TWO OF QUINOA'S CHROMOSOME SETS ARE EVOLUTIONARILY DESCENDED FROM ITS A GENOME DIPLOID ANCESTOR AND TWO SETS ARE DESCENDED FROM ITS B GENOME DIPLOID ANCESTOR. THUS, QUINOA'S ALLOTETRAPLOID CHROMOSOME COMBINATION, ALSO FOUND IN ITS IMMEDIATE WILD RELATIVE C. BERLANDIERI, ORIGINALLY AROSE VIA NATURAL HYBRIDIZATION BETWEEN THE TWO ANCESTRAL DIPLOIDS. THIS NATURAL HYBRIDIZATION EVENT PRODUCED THE WILD ALLOTETRAPLOID ANCESTOR C. BERLANDIERI, FROM WHICH ALLOTETRAPLOID QUINOA THEN EVOLVED UNDER DOMESTICATION PRIMARILY IN THE HIGH PLAINS REGION OF SOUTH AMERICA. OUR AIM IS TO DEVELOP THE ANCESTRAL B GENOME DIPLOID CHENOPODIUM FICIFOLIUM AS A SIMPLIFIED GENETIC MODEL SYSTEM IN WHICH TO IDENTIFY AND CHARACTERIZE GENES INFLUENCING ECONOMIC TRAITS, INCLUDING TRAITS OF INTEREST TO GROWERS (E.G., FAVORABLE PLANT ARCHITECTURE, REDUCED DAYS TO MATURITY, DISEASE RESISTANCE, AND OTHERS), AND TRAITS OF INTEREST TO CONSUMERS (SEED SIZE AND FLAVOR, NUTRITIONAL VALUE, COST, ETC). ONCE GENES OF INTEREST ARE IDENTIFIED, WE WILL SURVEY GENE-SPECIFIC DNA SEQUENCE DIVERSITY IN A DIVERSE SET OF GERMPLASM, INCLUDING REPRESENTATIVE QUINOA VARIETIES, GERMPLASM SAMPLES OF QUINOA'S WEEDY IMMEDIATE ANCESTOR, C. BERLANDIERI, AND IN REPRESENTATIVES OF THE ANCESTRAL A AND B GENOME DIPLOIDS. GENETIC CHARACTERIZATION OF THE MOST FAVORABLE GENE VARIANTS (ALLELES) WILL PROVIDE BREEDERS WITH INCREASED POWERS TO INCORPORATE FAVORABLE ALLELE COMBINATIONS INTO NEWLY BRED VARIETIES. FINALLY, WE WILL ASSESS THE EFFECTS OF TARGETED GENE MANIPULATION VIA GENE EDITING TECHNIQUES IN C. FICIFOLIUM, C. BERLANDIERI, AND IN QUINOA WITH THE ULTIMATE AIM OF FURTHER ACCELERATING BREEDING PROGRESS IN THIS PROMISING CROP. GENETIC, GERMPLASM, AND KNOWLEDGE RESOURCES GENERATED BY THIS PROJECT WILL BE WIDELY SHARED TO THE POTENTIAL BENEFIT OF QUINOA BREEDERS THROUGHOUT THE WORLD. THE ANTICIPATED OUTCOME OF THIS PROJECT IS THAT QUINOA BREEDERS IN DIFFERING ENVIRONMENTS WILL GAIN INCREASED POWERS TO ACHIEVE AND ACCELERATE THE DEVELOPMENT OF NEW QUINOA CULTIVARS THAT COMBINE ECONOMIC TRAITS WITH THE CHARACTERISTICS THAT IMPART ADAPTATION TO THE RESPECTIVE GEOGRAPHIC REGION AND ITS AGRONOMIC PRACTICES, THEREBY ENABLING MORE GROWERS AND CONSUMERS TO MORE WIDELY SHARE IN THE BENEFITS OF THIS NUTRITIOUS AND INCREASINGLY POPULAR FOOD CROP.
$649,825University System Of New Hampshire · · FY2022 · National Institute of Food and Agriculture
NF2-associated meningiomas: From omics discovery to targeted therapy
$649,818Vijaya Ramesh · Massachusetts General Hospital · R01 · FY2020 · NS
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS RESEARCH PROJECT ADDRESSES THE BRAG PROGRAM AREA OF INVESTIGATION AND MITIGATION OF UNINTENDED AND OFF-TARGET MODIFICATIONS BY GENOME EDITING TECHNOLOGIES. THE CYTOSINE BASE EDITORS (CBES), ENGINEERED FROM THE CRISPR-CAS SYSTEMS, ARE POISED TO REVOLUTIONIZE MODERN CROP BREEDING DUE TO THEIR PROMISING APPLICATIONS FOR TARGETED MUTAGENESIS, ALLELE REPLACEMENT, AND ENGINEERING OF QUANTITATIVE TRAITS. CBES CAN INTRODUCE PREMATURE STOP CODONS TO KNOCK OUT GENES AND EFFICIENTLY GENERATE HOMOZYGOUS MUTANTS WITHIN ONE GENERATION. HENCE, CBES HOLD GREAT PROMISE FOR MULTIPLEXED EDITING IN CROPS. IT HAS BEEN RECENTLY SHOWN THAT MULTIPLEXED EDITING BY CAS12A NUCLEASES COULD LEAD TO CHROMOSOMAL REARRANGEMENTS CAUSED BY CONCURRENT DNA DOUBLE-STRAND BREAKS (DSBS) IN PLANTS. UNLIKE CAS9 AND CAS12A NUCLEASES, CBES DERIVED FROM CAS9 AND CAS12A GENERALLY DO NOT PRODUCE DSBS IN THE PLANT GENOME. FOR EXAMPLE, CAS9-BASED CBES MAINLY NICK DNA, AND CAS12A-BASED CBES CANNOT CUT DNA. HENCE, IT IS ANTICIPATED THAT CBES ARE UNLIKELY TO GENERATE CHROMOSOMAL REARRANGEMENTS IN A MULTIPLEXED EDITING SETTING. TO INVESTIGATE THIS IMPORTANT ISSUE, WE WILL FIRST DEVELOP MULTIPLE IMPROVED CAS9-CBES AND CAS12A-CBES FOR HIGH-EFFICIENCY MULTIPLEXED EDITING IN RICE. THEN WE WILL CONDUCT GENOME-WIDE OFF-TARGET INVESTIGATIONS IN THE RICE PLANTS WITH MULTIPLEXED EDITS USING WHOLE-GENOME SEQUENCING. THE RELEVANCE OF THE PROPOSED PROJECT TO THE BRAG PROGRAM IS VERY SIGNIFICANT BECAUSE THE RESULTS WILL PROVIDE CRITICAL INFORMATION FOR THE GLOBAL REGULATORY AGENCIES TO COME UP WITH SCIENCE-BASED REGULATORY POLICIES AS WELL AS TO GUIDE REGULATORY DECISIONS ABOUT THE INTRODUCTION OF CRISPR-CAS GENERATED ORGANISMS INTO THE ENVIRONMENT. THE KNOWLEDGE GENERATED FROM OUR WORK WILL GREATLY AID PLANT SCIENTISTS PRACTICING GENE EDITING IN CROPS AS WELL AS FACILITATE THE DECISION-MAKING PROCESS AT REGULATORY AGENCIES SUCH AS THE USDA AND FDA.
$649,753University Of Maryland, College Park · · FY2024 · National Institute of Food and Agriculture
Genetic and physiologic regulation of pig islet development and function
$649,675Seung K Kim · Stanford University · R01 · FY2022 · DK
Cross-species development and credentialing of pediatric AML models
$649,623Jeffrey Alan Magee · Washington University · R01 · FY2025 · CA