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65,743 grants matching “single cell sequencing”
Endothelial Metabolism and Redox Imbalance in Vascular Disease
$2,264,097Tohru Fukai · Augusta University · P01 · FY2025 · HL
Endothelial Metabolism and Redox Imbalance in Vascular Disease
$2,264,097Tohru Fukai · Augusta University · P01 · FY2024 · HL
The Aging Pituitary/Gonadal Axis
$2,263,722George R Bousfield · Wichita State University · P01 · FY2023 · AG
YEAST GENETIC INTERACTION MAP
$2,262,200Johns Hopkins University · R01 · FY2004 · HG
Modifiable Drivers of Expansion and Malignant Transformation from Clonal Hematopoiesis
$2,261,447Margaret Goodell · Baylor College Of Medicine · P01 · FY2025 · CA
Center for pediatric tumor cell atlas
$2,261,333Kai Tan · Children'S Hosp Of Philadelphia · U2C · FY2020 · CA
EXPOSURE TO GALACTIC COSMIC RAYS (GCR) PRESENTS A HEALTH RISK TO ASTRONAUTS ON DEEP SPACE MISSIONS. TO STUDY THESE RISKS NASA IS DEVELOPING THE GCR SIMULATOR THAT WILL BE ABLE TO IRRADIATE CELL OR ANIMAL SAMPLES WITH COMBINATIONS OF IONS KNOWN TO BE PRESENT IN GCR. THIS DEVISE WILL BY NECESSITY IRRADIATE THESE SAMPLES AT DOSES AND DOSE RATES CONSIDERABLY HIGH THAN THAT FOUND IN SPACE IN ORDER TO PRODUCE STATISTICALLY MEANINGFUL RESULTS. TO PRODUCE THE BEST SIMULATIONS DOSE RATES AND EXPOSURE SEQUENCES WILL NEED TO BE OPTIMIZED. THIS PROPOSAL WILL ENDEAVOR TO OPTIMIZE THESE PARAMETERS BY MEASURING THE INDUCTION OF CHROMOSOME ABERRATIONS. MOST OF THESE ABERRATIONS ARE EXCHANGES OF CHROMOSOMAL SEGMENTS THAT COME ABOUT WHEN RADIATION DAMAGE SEVERS CHROMOSOMES. NORMALLY CELLS CAN REPAIR THESE BREAKS BUT ON OCCASION IF TWO OR MORE BREAKS ARE CLOSE TO ONE ANOTHER A MISTAKE CAN BE MADE WHEREBY THE CELL JOINS BREAK ENDS TO INAPPROPRIATE PARTNERS CAUSING AN EXCHANGE OF CHROMOSOMAL SEGMENTS. THE DAMAGE FORMING THESE BREAKS IS CAUSED BY IONIZATIONS ALONG THE PATHS (TRACKS) THAT IONS TAKE AS THEY PASS THROUGH A MEDIUM. WHILE IN SOME CASES ALL THE BREAKS NECESSARY FOR AN EXCHANGE TO FORM OCCUR ALONG A SINGLE PARTICLE TRACK IN OTHER CIRCUMSTANCES BREAKS ARE FORMED ALONG SEPARATE AND INDEPENDENT TRACKS IN A PROCESS REFERRED TO AS TRACK INTERACTION. TRACK INTERACTION EVENTS BECOME IMPORTANT AT HIGHER DOSES WHEN THE NUMBER OF TRACKS PRODUCE DAMAGE THAT IS SUFFICIENTLY CLOSE TO INTERACT INCREASES. TRACK INTERACTIONS ARE NOT LIKELY TO OCCUR AT THE DOSES THOUGHT TO BE FOUND IN SPACE BUT WILL CERTAINLY HAPPEN AT THE HIGHER DOSES REQUIRED FOR GCR SIMULATIONS AND POTENTIALLY SKEW THE RESULTS. ONE STRATEGY TO AVOID TRACK INTERACTIONS IS TO LOWER THE DOSE RATE. BY SPACING OUT THE TIME OVER WHICH IONS PASS THROUGH A CELL BREAKS FORMING EARLY IN THE TIME FRAME HAVE AN OPPORTUNITY TO BE REPAIRED BEFORE OTHER BREAKS FORMING SPATIALLY CLOSE ENOUGH TO INTERACT WITH THEM ARRIVE ON THE SCENE. THIS PRODUCES A REDUCTION IN THE FREQUENCY OF CHROMOSOME EXCHANGES. AS THE DOSE RATE DECREASES FURTHER A POINT IS REACHED WHERE VIRTUALLY ALL THE EXCHANGES RESULT FROM SINGLE TRACK ACTION. AT THIS LIMITING LOW DOSE RATE NO ADDITIONAL REDUCTION IN CHROMOSOME EXCHANGE FREQUENCY IS POSSIBLE BY FURTHER REDUCTION IN THE DOSE RATE. THESE RESULTS WILL BE DIRECTLY SCALABLE TO THE LOW DOSES AND DOSE RATES PRESENT IN SPACE. SPECIFIC AIM 1 OF OUR PROPOSAL WILL ENDEAVOR TO DETERMINE THE LIMITING LOW DOSE RATE FOR PROTONS AT THE ENERGY STATED IN THE NRA. THIS WILL BE ACCOMPLISHED BY IRRADIATING CELLS WITH A SERIES OF DOSES AT DOSE RATES WE ESTIMATE WILL BE CLOSE TO THE LIMITING LOW DOSE RATE AND LOOKING FOR CHROMOSOME EXCHANGES. WHEN ADDITIONAL REDUCTION IN DOSES RATE FAILS TO PRODUCE ANY FURTHER DECREASE IN EXCHANGES AS A FUNCTION OF DOSE WE WILL BE AT THE LIMITING LOW DOSE RATE. THE GCR SIMULATOR WILL BE IRRADIATING SAMPLES WITH A NUMBER OF DIFFERENT ION BEAMS IN ORDER TO BETTER SIMULATE THE NATURE OF THE MIXED ION FIELD FOUND IN SPACE. THE HEAVIER IONS IN THE GCR SPECTRUM WILL BEHAVE DIFFERENTLY FROM THE LIGHTER IONS. THE HEAVY IONS PRODUCE MORE DAMAGE ALONG THEIR TRACKS; SO MUCH SO THAT VIRTUALLY ALL CHROMOSOME EXCHANGES ARE FORMED VIA SINGLE TRACK ACTION. IN THIS CASE WE WILL NEED TO DETERMINE THE OPTIMAL TIME NEEDED FOR REPAIR TO OCCUR BETWEEN IRRADIATIONS WITH THE SUBSEQUENT IONS BEAMS TO AVOID TRACK INTERACTION. SPECIFIC AIM 2 WILL ADDRESS THESE CONCERNS BY VARYING THE TIME BETWEEN ION BEAMS. MUCH LIKE THE DOSE RATE EXPERIMENTS AS WE EXTEND THE TIME BETWEEN IRRADIATIONS THE PROBABILITY FOR TRACK INTERACTION SHOULD BE REDUCED. ONCE WE REACH A LEVEL WHERE NO FURTHER CHROMOSOME EXCHANGE FREQUENCY REDUCTIONS ARE OBSERVED WE WILL HAVE REACHED THE OPTIMAL POINT FOR IRRADIATION DELAY. SEQUENCE MAY ALSO BE IMPORTANT IN THAT REGARD AND ADDITIONAL EXPERIMENT WILL SEARCH FOR THE BEST SEQUENCE THAT MINIMIZES TRACK INTERACTION.
$2,261,083University Of Texas Medical Branch At Galveston · · FY2020 · National Aeronautics and Space Administration
Illuminating Function of the Understudied Druggable Kinome
$2,259,159Gary L. Johnson · Univ Of North Carolina Chapel Hill · U24 · FY2020 · DK
Construction of an integrated immune - vascular brain - chip as a platform for the study, drug screening, and treatments of Alzheimer's disease
$2,259,000Li-Huei Tsai · Massachusetts Institute Of Technology · UG3 · FY2019 · NS
Biophysics of Large Membrane Channels
$2,257,973Sergey Bezrukov · Eunice Kennedy Shriver National Institute Of Child Health & Human Development · ZIA · FY2025 · HD
BRAIN CONNECTS: PatchLink, scalable tools for integrating connectomes, projectomes, and transcriptomes
$2,256,846Staci A Sorensen · Allen Institute · U01 · FY2025 · NS
Comparative Analysis Of Completely Sequenced Genomes
$2,255,387Eugene V Koonin · National Library Of Medicine · ZIA · FY2025 · LM
COBRE: Center for Computational Biology of Human Disease
$2,253,073David M Rand · Brown University · P20 · FY2023 · GM
Mechanism Of Action And Functions Of The Gli-related Proteins Glis 1-3
$2,252,832Anton M Jetten · National Institute Of Environmental Health Sciences · ZIA · FY2024 · ES
Isogenic Human Pluripotent Stem Cell-Based Models of Human Disease Mutations
$2,252,820Chad Albert Cowan · Broad Institute, Inc. · R01 · FY2016 · DK
Development and validation of AAV vectors to manipulate specific neuronal subtypes and circuits involved in epilepsy and psychiatric disorders across mammalian species.
$2,252,723Gordon J Fishell · Broad Institute, Inc. · UH3 · FY2024 · MH
Phylodynamics of Cell Populations
$2,252,479Kenneth Hoehn · Dartmouth College · R35 · FY2025 · GM
SPORE: Targeted Therapies for Glioma
$2,252,175Tracy T Batchelor · Brigham And Women'S Hospital · P50 · FY2021 · CA
Illuminating Function of the Understudied Druggable Kinome
$2,252,146Gary L. Johnson · Univ Of North Carolina Chapel Hill · U24 · FY2022 · DK
Illuminating Function of the Understudied Druggable Kinome
$2,251,844Gary L. Johnson · Univ Of North Carolina Chapel Hill · U24 · FY2021 · DK
Revealing the single cell determinants of brain relevant to persistent HIV infection and opioid use disorder
$2,251,781Tariq M Rana · University Of California, San Diego · U01 · FY2021 · DA
Role of apoE-mediated meningeal lymphatic remodeling in the pathophysiology of Alzheimerâs disease
$2,250,745Sandro Da Mesquita · Mayo Clinic Jacksonville · RF1 · FY2023 · AG
Innate and Adaptive Immune Responses in SARS-CoV-2 infection (COVID-19)
$2,250,196Daniel Cesar Douek · National Institute Of Allergy And Infectious Diseases · ZIA · FY2023 · AI
SPORE: Targeted Therapies for Glioma
$2,250,039Tracy T Batchelor · Brigham And Women'S Hospital · P50 · FY2022 · CA
Impact of Bacterial-Animal Lateral Gene Transfer on Human Health
$2,250,000Julie Dunning Hotopp · University Of Maryland Baltimore · DP2 · FY2010 · OD