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17,828 grants matching “crispr”
CRISPR Capture, Destroy, and Counter-Attack Mechanisms
$650,000Michael P Terns · University Of Georgia · R35 · FY2021 · GM
** 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
Regulation of Craniofacial Development by ALX Transcription Factors
$649,936Rulang Jiang · Cincinnati Childrens Hosp Med Ctr · R01 · FY2024 · DE
** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** LONG-LIVED PERENNIAL PLANTS LIKE TREES ARE IMPORTANT IN PROVIDING FOOD, FIBER AND ECOSYSTEM SERVICES. NITROGEN IS AN ESSENTIAL NUTRIENT THAT IMPACTS PLANT GROWTH AND PRODUCTIVITY. ANNUAL PLANTS MUST ACQUIRE AND ASSIMILATE NITROGEN FROM SOIL TO SUPPORT GROWTH AND DEVELOPMENT. IN CONTRAST, NITROGEN ACQUISITION AND USE IN PERENNIAL PLANTS AND TREES IS MORE COMPLEX THAN ANNUAL PLANTS SINCE A MAJOR PORTION OF NITROGEN DEMAND IS MET BY INTERNAL SEASONAL CYCLING THAT REUSES ASSIMILATED AND REDUCED NITROGEN. SEASONAL NITROGEN CYCLING IS AN ANNUAL RECURSIVE PROCESS THAT INCREASINGLY CONTRIBUTES TO THE NITROGEN BUDGET AS TREES AGE. CONSEQUENTLY, SEASONAL NITROGEN CYCLING AFFORDS A COMPETITIVE ADVANTAGE IN NITROGEN LIMITED ENVIRONMENTS AND IS IMPORTANT TO THE ECOLOGY OF NITROGEN USE IN TREES AND IS A MAJOR FACTOR CONTRIBUTING TO NITROGEN USE EFFICIENCY.THE CONTRIBUTION OF STORED NITROGEN TO FOREST TREE NUTRIENT BUDGETS VARIES AMONG SPECIES. AND FOR POPLARS (POPULUS) SPRING GROWTH RELIES ALMOST EXCLUSIVELY ON NITROGEN FROM STORAGE RESERVES. BESIDES BEING IMPORTANT TO FOREST TREES, SEASONAL NITROGEN CYCLING AND NITROGEN RESERVE MOBILIZATION HAS LONG BEEN RECOGNIZED AS BEING IMPORTANT IN FRUIT TREES. IN THIS PROJECT, STATE-OF-THE-ART CRISPR GENE EDITING METHODS WILL BE USED IN COMBINATION WITH MOLECULAR BIOLOGY RESEARCH APPROACHES TO UNDERSTAND THE MOLECULAR AND GENETIC BASIS OF HOW SEASONAL NITROGEN CYCLING IS CONTROLLED AND REGULATED IN POPLAR. THIS BUILDS UPON THE DISCOVERY THAT THE PLANT HORMONE ETHYLENE REPRESSES THE EXPRESSION OF THE POPLAR BARK STORAGE PROTEIN GENES, WHICH PLAY A CENTRAL ROLE IN SEASON NITROGEN CYCLING. THIS WILL BE ACCOMPLISHED THROUGH (1) CRISPR GENE EDITING OF GENES THAT APPEAR TO REGULATE THIS PROCESS, (2) BIOCHEMICAL APPROACHES TO TEST IF THE PROTEINS ENCODED BY THESE GENE INTERACT, (3) MOLECULAR BIOLOGY APPROACHES TO DETERMINE IF THESE PROTEIN FACTORS BIND TO DNA REGULATORY SEQUENCES IN THE BARK STORAGE PROTEIN GENES, AND (4) DISCOVER IF OTHER REGULATORY FACTORS REGULATE BARK STORAGE PROTEIN GENE EXPRESSION AND SEASONAL NITROGEN CYCLING USING CRISPR-BASED SCREENS.THIS RESEARCH WILL ADVANCE UNDERSTANDING OF SEASONAL NITROGEN CYCLING AND DIRECTLY ADDRESSES THE RESEARCH PRIORITIES OF THE PHYSIOLOGY OF AGRICULTURAL PLANTS PROGRAM (A1152). SPECIFICALLY, THIS RESEARCH FALLS WITHIN THE RESEARCH PRIORITY OF NUTRIENT UPTAKE, ASSIMILATION, ACCUMULATION, AND/OR UTILIZATION, PARTICULARLY INCREASE EFFICIENCY IN USING NITROGEN, OR PHOSPHORUS OR OTHER SUPPLEMENTAL NUTRIENTS. IN ADDITION, THIS PROJECT WILL ALSO ADVANCE KNOWLEDGE CONCERNING REGULATORY FACTORS INVOLVED IN THE ESTABLISHMENT AND REGULATION OF N SOURCE-SINK RELATIONSHIPS.
$649,929University Of Maryland, College Park · · FY2024 · National Institute of Food and Agriculture
CRISPR-enhanced adipocyte browning to improve glucose tolerance in obesity and diabetes
$649,900Michael P Czech · Univ Of Massachusetts Med Sch Worcester · R01 · FY2021 · DK
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
** 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 SPOTTED WING DROSOPHILA, DROSOPHILA SUZUKII, IS A WORLDWIDE CROP PEST OF SOFT-SKINNED FRUITS. CURRENT METHODS TO CONTROL MANY AGRICULTURAL PESTS, SUCH AS D. SUZUKII, RELY ON EXPENSIVE, BROAD-SPECTRUM INSECTICIDES, WHICH HAVE VARIABLE EFFICACY, ARE CHALLENGING TO USE DUE TO THE TIMING OF FRUIT INFESTATION AND INCREASE THE RISK D. SUZUKII EVOLVING RESISTANCE TO THE INSECTICIDE. HOWEVER, THERE ARE NO PRACTICAL ALTERNATIVES TO MANAGING D. SUZUKII INFESTATION, AND IT IS LIKELY THAT, UNLESS MORE EFFECTIVE CONTROL MEASURES ARE DEVELOPED, THIS PEST WILL CONTINUE TO SPREAD AND NEGATIVELY IMPACT FRUIT PRODUCTION.GENETIC TECHNOLOGIES CAN COMPLEMENT EXISTING PEST MANAGEMENT STRATEGIES FOR D. SUZKUII AND OTHER AGRICULTURAL PESTS. THIS PROPOSAL AIMS TO GENERATE TOOLS TO MONITOR, IMPROVE, AND BETTER UNDERSTAND THE BEHAVIOR OF A NEW GENETIC TECHNOLOGY, PRECISION-GUIDED STERILE INSECT TECHNIQUE (PGSIT), AND OTHER CRISPR-BASED TECHNOLOGIES IN THE FIELD. THE FIRST TOOL, SENSITIVE ENZYMATIC NUCLEIC ACID SEQUENCE REPORTER (SENSR), IS A DIAGNOSTIC SYSTEM DESIGNED TO RAPIDLY DETECT PGSIT-SPECIFIC AND CRISPR-ASSOCIATED DNA. RAPID IDENTIFICATION OF THE DNA OF THESE TECHNOLOGIES IS VITAL FOR ASSESSING THE RISK AND PERFORMANCE OF GENETIC BIOCONTROL TOOLS. THEY CAN BE USED AS A RAPID TOOL TO MONITOR THE BEHAVIOR OF GENETICALLY ENGINEERED (GE) TECHNOLOGIES IN THE FIELD AND THEIR POTENTIAL SPREAD INTO NEARBY AREAS.ANOTHER TECHNOLOGY WE AIM TO DEVELOP IN D. SUZUKII IS SEPARATOR (SEXING ELEMENT PRODUCED BY ALTERNATIVE RNA-SPLICING OF A TRANSGENIC OBSERVABLE REPORTER). SEPARATOR CAN IMPROVE THE QUALITY AND ACCURACY OF FIELD RELEASES OF D. SUZUKII. FOR EXAMPLE, ONLY D. SUZUKII FEMALES CAUSE DAMAGE TO FRUIT, SO WE WANT TO REDUCE CROP DAMAGE WE ONLY WANT TO RELEASE MALES IN GENETIC CONTROL PROGRAMS. ADDITIONALLY, IF THERE ARE FREQUENT ERRORS IN THE SEX-SORTING OF PGSIT LINES PRIOR TO MATING IN THE LABORATORY, THEN THERE IS A HIGHER RISK OF RELEASING FERTILE FLIES. WE WILL, THEREFORE, ENGINEER AND OPTIMIZE A SEPARATOR SYSTEM IN D. SUZUKII THAT SHOULD MINIMIZE OR ELIMINATE THE RISK OF MATING ERRORS THAT MIGHT RESULT IN THE RELEASE OF FEMALES THAT DAMAGE CROPS OR FERTILE INDIVIDUALS.WE WILL ALSO EVALUATE THE BEHAVIOR OF PGSIT IN RESPONSE TO CHANGES IN ENVIRONMENTAL CONDITIONS AND WHETHER PGSIT COULD HELP MITIGATE THE GENE FLOW OR SPREAD OF GENE TECHNOLOGIES. THESE STUDIES WILL ENSURE WE UNDERSTAND HOW PGSIT WILL PERFORM IN A CHANGING ENVIRONMENT AND HOW IT CAN BE USED TO REMOVE OTHER GE TECHNOLOGIES FROM THE FIELD. THESE STUDIES WILL BE PERFORMED IN THE LABORATORY AND MODELED TO UNDERSTAND HOW THEY WILL BEHAVE ON A LARGER SCALE.STUDIES OF THESE EMERGING TECHNOLOGIES ARE ESSENTIAL FOR THE RESPONSIBLE DEVELOPMENT AND MANAGEMENT OF GENETICALLY ENGINEERED (GE) TECHNOLOGIES FOR AGRICULTURAL PEST CONTROL. THIS WORK WILL FOCUS ON A MORE COMPREHENSIVE EVALUATION OF THE CRISPR-BASED SIT TECHNOLOGY, PGSIT, FOR D. SUZUKII CONTROL AND TECHNOLOGIES THAT COMPLEMENT ITS MONITORING AND SUCCESS IN,THE FIELD. THIS WILL ALLOW US TO BUILD TOOLS AND KNOWLEDGE TO SUPPRESS PEST POPULATIONS AND BETTER CONFINE AND MANAGE MORE INVASIVE GENETIC TECHNOLOGIES.
$649,414University Of California, San Diego · · FY2024 · National Institute of Food and Agriculture
Proteomics Integration and Expansion of Downstream Analysis Capabilities into the CReD Portal
$649,398Nevan J Krogan · University Of California, San Francisco · U01 · FY2020 · MH
Structure And Function In Retinal Neurons
$649,058Ralph Nelson · National Institute Of Neurological Disorders And Stroke · ZIA · FY2021 · NS
Functional Characterization of Glioma GWAS Variants
$649,042Rose Kamyee Lai · University Of Southern California · R01 · FY2017 · CA
Functional Characterization of Glioma GWAS Variants
$649,042Rose Kamyee Lai · University Of Southern California · R01 · FY2018 · CA
MG53 function in muscle aging
$649,040Jianjie Ma · University Of Virginia · R01 · FY2022 · AG
Mapping heritable chromatin loop variants with allele-specific Hi-C analysis
$648,910Fulai Jin · Case Western Reserve University · R01 · FY2025 · HG
Folic Acid Supplementation and Colitis-associated Colon Carcinogenesis
$648,814Margie L. Clapper · Research Inst Of Fox Chase Can Ctr · R01 · FY2025 · CA
Sequence analysis of hemotological traits in African Americans
$648,810Ethan Mather Lange · University Of Colorado Denver · R01 · FY2018 · HL
Activation and Inhibition Mechanisms of Calcium-Activated Nonselective Cation Channels
$648,594Jie Zheng · University Of California At Davis · R01 · FY2025 · NS
Targeting proteostatic mechanisms to inhibit LRRK2-mediated neurodegeneration and neuropathology
$648,555Annie E Hiniker · University Of California, San Diego · R01 · FY2023 · NS
Project 1: Determination of molecular differences caused by tauopathy-associated H1 and H2 haplotypes
$648,438Alison M Goate · Icahn School Of Medicine At Mount Sinai · U54 · FY2025 · NS
Defining the role of cytomegalovirus in glioblastoma therapies
$648,427Sean Edward Lawler · Brown University · R01 · FY2023 · CA
Characterization of novel insulin resistance genes by gene editing, high-throughput phenotyping and in vivo studies
$648,352Joshua Wiley Knowles · Stanford University · R01 · FY2020 · DK
Define the oncogenic role of METTL3 in the pathogenesis of chronic lymphocytic leukemia
$648,241Lili Wang · Beckman Research Institute/City Of Hope · R01 · FY2025 · CA
PI3K Pathway Mutations in Head and Neck Cancer
$648,229Jennifer R Grandis · University Of California, San Francisco · R01 · FY2019 · DE
A Versatile Chemical-Genetic Approach to Determine Bases for Arrhythmogenesis and Sodium Channelopathies
$648,192Christopher A Ahern · University Of Iowa · R01 · FY2025 · HL
Binding of Epstein Barr Virus EBNA2 Unifies Multiple Sclerosis Genetic Mechanisms
$648,175Matthew Tyson Weirauch · Cincinnati Childrens Hosp Med Ctr · R01 · FY2023 · NS