Sort
17,828 grants matching “crispr”
DROSOPHILA SUZUKII, ALSO KNOWN AS SPOTTED WING DROSOPHILAD. SUZUKII LARVAE ARE CAPABLE OF INFESTING A WIDE RANGE OF HOST FRUIT BUT APPEAR TO BE MOST SIGNIFICANT PESTS IN STONE FRUITS (PEACH, CHERRY, AND PLUM) AND BERRIES (CANEBERRIES, BLUEBERRIES, AND STRAWBERRIES). UNLIKE MOST OTHER DROSOPHILA SPECIES, FEMALE D. SUZUKII ARE ABLE TO PIERCE THE SKIN OF SOFT FRUITS AND LAY THEIR EGGS INSIDE THE FRUIT. D. SUZUKII HAS A SHORT GENERATION TIME AND MULTIPLE GENERATIONS PER YEAR. IN CONTRAST, THE LARGER FRUIT FLIES (RHAGOLETIS SP.) NATIVE TO NORTH AMERICA HAVE ONLY ONE GENERATION PER YEAR. D. SUZUKII IS ENDEMIC IN ASIA BUT IN 2008 THE FLY WAS FOUND IN CALIFORNIA. SINCE THEN, D. SUZUKII HAS SPREAD RAPIDLY AND IS NOW FOUND IN TEMPERATE REGIONS IN NORTH AMERICA AND EUROPE. IMPORTANTLY, IN THE USA, ANY FRUIT THAT CONTAIN DEVELOPING D. SUZUKII LARVAE CAN CAUSE AN ENTIRE SHIPMENT TO BE REJECTED! GROWERS ARE CURRENTLY USING BROAD SPECTRUM INSECTICIDES TO PROTECT FRUIT FROM DAMAGE CAUSED BY D. SUZUKII. FOR EXAMPLE, GROWERS IN NORTH CAROLINA ARE USING MORE FREQUENT INSECTICIDE APPLICATIONS TO MANAGE THIS INVASIVE FRUIT FLY BUT THE EFFECTIVENESS OF THESE TREATMENTS IS WEATHER DEPENDENT. IT IS ALSO ANTICIPATED THAT D. SUZUKII WILL DEVELOP RESISTANCE TO SOME OF THE MORE COMMONLY USED INSECTICIDES. THEREFORE, NON-CHEMICAL MEANS FOR CONTROLLING D. SUZUKII ARE NEEDED.COCHLIOMYIA HOMINIVORAX, ALSO KNOWN AS THE NEW WORLD SCREWWORMC. HOMINIVORAX IS ADEVASTATING PEST OF WARM-BLOODED ANIMALS AND CAUSES MAJOR ECONOMIC LOSSES (>$4BILLION ANNUALLY). FEMALE SCREWWORM FLIESLAY THEIR EGGS IN OPEN WOUNDS OR A NATURAL ORIFICE. THE HATCHED LARVAE THEN FEED ON THE ANIMAL'S LIVING TISSUE. ANIMALS WITH SEVERE SCREWWORM INFESTATIONS MAY DIE IF UNTREATED. HOWEVER, MOST CASES ARE LESS SEVERE BUT THEY ARE ECONOMICALLY IMPORTANT BECAUSE THE ANIMAL SUFFERS WEIGHT LOSS AND CARCASSES AND HIDES ARE DAMAGED. IN THE FIRSTAND ARGUABLY MOST SUCCESSFUL GENETIC CONTROL PROGRAM, C. HOMINIVORAX WAS ERADICATED FROM THE USA, MEXICO AND CENTRAL AMERICA THROUGH USE OF THE STERILE INSECT TECHNIQUE OR SIT. SIT INVOLVES REGULAR RELEASES OF LARGE NUMBERS OF STERILE FLIES OVER THE TARGETED AREA. FEMALE FLIES IN THE AREA THAT MATE WITH STERILE MALES DO NOT PRODUCE ANY OFFSPRING. SCREWWORM REMAINS IN THE LARGE CARIBBEAN ISLANDS (E.G. CUBA, HISPANIOLA, JAMAICA) AND MOST OF SOUTH AMERICA. TO PREVENT RE-INFESTATION FROM SOUTH AMERICA, STERILIZED FLIES ARE CURRENTLY BEING CONSTANTLY RELEASED IN A "BUFFER ZONE" IN PANAMA ALONG THE BORDER WITH COLOMBIA. THE SCREWWORM MASS REARING FACILITY IS IN PACORA, PANAMA AND IS RUN BY THE U.S.-PANAMANIAN COMMISSION FOR THE ERADICATION AND PREVENTION OF SCREWWORMS (COMISIÓN PANAMÁ-ESTADOS UNIDOS PARA LA ERRADICACIÓN Y PREVENCIÓN DEL GUSANO BARRENADOR DEL GANADO OR COPEG). CURRENTLY ABOUT 20 MILLION FLIES ARE REARED EACH WEEK. ALL OF OUR WORK ON SCREWWORM GENETIC ENGINEERING HAS BEEN CONDUCTED IN THIS FACILITY.THEOUTBREAK OF SCREWWORM IN 2016 IN THE FLORIDA KEYS SHOWS THAT THE USA REMAINS VULNERABLE TO THE REINTRODUCTION OF THIS PEST SPECIES. FORTUNATELY, WITH REGULAR RELEASES OF STERILE FLIES FROM THE PANAMA FACILITY, THE OUTBREAK WAS STOPPED BEFORE FLIES SPREAD TO THE MAINLAND, WHERE THEY WOULD HAVE BEEN A DANGER TO THE FLORIDA LIVESTOCK INDUSTRY.WHILE SUCCESSFUL, SIT IS EXPENSIVE DUE TO THE LARGE NUMBERS OF FLIES THAT NEED TO BE REARED. MORE EFFICIENT GENETIC CONTROL METHODS ARE NEEDED IF SCREWWORM IS TO BE ERADICATED FROM THE CARIBBEAN OR SOUTH AMERICA.OUR APPROACH: Y-LINKED CRISPR/CAS9 SYSTEMS THAT CAUSE FEMALE LETHALITYTHE CRISPR REVOLUTION OF GENE EDITING COULD LEAD TO SEVERAL NOVEL GENETIC SYSTEMS FOR EFFICIENT METHODS FOR SUPPRESSION OF PEST POPULATIONS. ONE SYSTEM THAT HAS RECEIVED CONSIDERABLE ATTENTION IN THE POPULAR PRESS AND SCIENTIFIC LITERATURE ARE CAS9-BASED HOMING GENE DRIVES.THESE GENETIC SYSTEMS HAVE THE POTENTIAL TO BE VERY EFFICIENT AND THUS VERY ECONOMICAL FOR PEST SUPPRESSION. HOWEVER, THE RELEASED INSECTS WOULD BE VERY DIFFICULT TO CONTAIN AS THE SYSTEM IS SELF-PROPAGATING AND DESIGNED TO SPREAD. THE CURRENT SYSTEMS ALSO APPEAR TO BREAKDOWN VERY QUICKLY DUE TO RESISTANCE. WE ARE PROPOSING TO USE A DIFFERENT SYSTEM KNOWN AS Y-LINKED EDITOR OR YLE. WHILE THIS SYSTEM IS NOT A GENE DRIVE, MODELING HAS SHOWN THAT YLES COULD BE SIGNIFICANTLY MORE EFFICIENT FOR POPULATION SUPPRESSION THAN SIT .THUS, OUR GOAL IS TO MAKE D. SUZUKII AND C. HOMINIVORAX YLE STRAINS AND THEN ASSESS THEIR POTENTIAL FOR POPULATION SUPPRESSION IN LABORATORY CAGE EXPERIMENTS.YLE STRAINSA YLE STRAIN HAS TWO ESSENTIAL COMPONENTS IN ONE GENE CONSTRUCT. THE FIRST COMPONENT IS THE CAS9 NUCLEASE. EXPRESSION OF THE NUCLEASE IS DRIVEN BY A GENE PROMOTER THAT IS ACTIVE IN THE MALE GERMLINE (TESTES). THE SECOND COMPONENT ARE GUIDE RNA(S) THAT AREA ALSO EXPRESSED IN THE MALE GERMLINE. THE GUIDE RNA GUIDE THE CAS9 NUCLEASE TO A GENE. CLEAVAGE OF THE GENE BY CAS9 AND MISREPAIR WILL LEAD TO A MUTANT GENE THAT IS NOT FUNCTIONAL. WE WILL IDENTIFY GUIDE RNAS FOR X-LINKED GENES THAT ARE "HAPLOINSUFFICIENT", THAT IS TWO COPIES OF THE GENE ARE NEEDED FOR VIABILITY. THUS THE SPERM PRODUCED BY THE YLE MALE WILL CARRY MUTANT X-LINKED GENES. AFTER MATING, ANY FEMALE OFFSPRING WILL INHERIT THE MUTANT X CHROMOSOME FROM THEIR FATHER AND WILL NOT BE VIABLE. ANY MALE OFFSPRING WILL INHERIT THE NORMAL CHROMOSOME FROM THEIR MOTHER AND WILL BE VIABLE. THEY WILL ALSO INHERIT THE YLE FROM THEIR FATHER. THE YLE MALES ARE THEN FREE TO SEEK OUT AND MATE WITH WILD TYPE FEMALES AND THE CYCLE IS REPEATED.IN THE INITIAL PHASE OF THIS PROJECT WE WILL IDENTIFY SUITABLE GENE PROMOTERS AND GUIDE RNAS. TRANSGENIC YLE STRAINS WILL THEN BE MADE THROUGH STANDARD INJECTION OF FLY EMBRYOS WITH DNA AND PROTEIN. THE POTENTIAL OF THE YLE STRAINS FOR POPULATION SUPPRESSION WILL BE EVALUATED USING LABORATORY CAGE EXPERIMENTS. ADDITIONAL CAGE EXPERIMENTS WILL BE DONE TO DETERMINE THE POTENTIAL OF YLE TO SPREAD TO A NEIGHBORING POPULATION, WHICH WILL AID ANY FUTURE ASSESSMENT FOR A FIELD RELEASE.
$498,569North Carolina State University · · FY2020 · National Institute of Food and Agriculture
Structure, function, and evolution of the Cryptococcus MAT locus
$498,319Joseph Heitman · Duke University · R01 · FY2022 · AI
Defining and targeting epigenetic plasticity-driven drug resistance and immune escape in melanoma
$498,307Keiran Smalley · H. Lee Moffitt Cancer Ctr & Res Inst · R01 · FY2022 · CA
Leveraging multi-species single cell omic datasets to study the evolution of cell type-specific gene regulatory networks
$498,204Sushmita Roy · University Of Wisconsin-Madison · R01 · FY2022 · HG
Understanding intrinsic resistance to direct KRAS inhibition in colorectal cancers
$498,202John D Gordan · University Of California, San Francisco · R37 · FY2024 · CA
Genetics and Pathobiology of Disorders of Keratinization
$498,170Keith A Choate · Yale University · R01 · FY2015 · AR
Genetic variants guiding pathogenicity of colitogenic T cells
$498,064John Philip Ray · Benaroya Research Inst At Virginia Mason · R01 · FY2024 · DK
The novel smooth muscle-specific lncRNA CARMN is a critical regulator of smooth muscle phenotype
$498,063Jiliang Zhou · Augusta University · R01 · FY2020 · HL
Targeting oncogenic Myb fusions in salivary gland cancer with the elongation inhibitor SVC112
$497,893Antonio Jimeno · University Of Colorado Denver · R01 · FY2025 · DE
Targeting oncogenic Myb fusions in salivary gland cancer with the elongation inhibitor SVC112
$497,893Antonio Jimeno · University Of Colorado Denver · R01 · FY2021 · DE
Targeting oncogenic Myb fusions in salivary gland cancer with the elongation inhibitor SVC112
$497,893Antonio Jimeno · University Of Colorado Denver · R01 · FY2023 · DE
Regulators of Cancer Immunotherapy Response
$497,881Xiaole Shirley Liu · Dana-Farber Cancer Inst · R01 · FY2019 · CA
New Targets for Reproductive Control of Mosquito Vectors
$497,864Laura C Harrington · Cornell University · R01 · FY2018 · AI
Epigenetic mechanisms of transcriptional activation of a novel oncogenic ALK variant in cancer
$497,774Ping Chi · Sloan-Kettering Inst Can Research · R01 · FY2018 · CA
Foxp2 genetic control of sex differences in amygdala-driven social behavior
$497,652Joshua G Corbin · Children'S Research Institute · R21 · FY2024 · MH
Integrating Omics, Networks, and Functional Studies in COPD and IPF
$497,617Edwin K Silverman · Weill Medical Coll Of Cornell Univ · P01 · FY2023 · HL
Novel insulin-sensitizing NASH/diabetes drugs.
$497,526Timothy R Peterson · Bioio, Llc · R42 · FY2021 · DK
Novel insulin-sensitizing NASH/diabetes drugs.
$497,526Timothy R Peterson · Bioio, Llc · R42 · FY2020 · DK
Novel insulin-sensitizing NASH/diabetes drugs.
$497,526Timothy R Peterson · Bioio, Llc · R42 · FY2022 · DK
uORF-mediated Translational Control of Cardiac Transcription Factor Expression
$497,488Peng Yao · University Of Rochester · R01 · FY2024 · HL
Integrating Omics, Networks, and Functional Studies in COPD and IPF
$497,427Edwin K Silverman · Weill Medical Coll Of Cornell Univ · P01 · FY2022 · HL
Characterizing TP53 and PPM1D mutations as resistance drivers to radiation therapy in Diffuse Intrinsic Pontine Gliomas
$497,259Rameen Beroukhim · Broad Institute, Inc. · R01 · FY2019 · CA
Mosquito hydration status as a mechanism that alters pre-feeding host interactions and post-feeding physiology
$497,132Josh B. Benoit · University Of Cincinnati · R01 · FY2023 · AI
BRC-BIO: MediCARGO- Decoding peptide perception during Medicago-Sinorhizobium symbiosis using CRISPR-cas9 As a Reverse Genetics tool
$497,100Sonali Roy · Tennessee State University · · FY2022 · BIO
Biology and novel therapy of AML expressing somatic or germline mutant RUNX1
$496,911Kapil N. Bhalla · University Of Tx Md Anderson Can Ctr · R01 · FY2021 · CA