grant
Project 2 - Verification and Molecular Mechanisms of T1D Modifier Mutations
Organization UT SOUTHWESTERN MEDICAL CENTERLocation DALLAS, UNITED STATESPosted 13 Jun 2023Deadline 31 May 2028
NIHUS FederalResearch GrantFY20251-Ethyl-1-nitrosoureaAccelerationActin FilamentsActinsAffectAllelesAllelomorphsAnimalsAntigenic DeterminantsApoproteinsApoptoticAssayAttentionB blood cellsB cellB cellsB-CellsB-LymphocytesB-cellB9 endocrine pancreasBeta CellBindingBinding DeterminantsBioassayBiological AssayBody TissuesBrittle Diabetes MellitusCD152CD152 AntigenCD152 GeneCRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCTLA 4CTLA-4 GeneCTLA4CTLA4 geneCTLA4-TMCachectin ReceptorsCandidate Disease GeneCandidate GeneCas nuclease technologyCausalityCell BodyCell Communication and SignalingCell FunctionCell IsolationCell LocomotionCell MigrationCell MovementCell PhysiologyCell ProcessCell SegregationCell SeparationCell Separation TechnologyCell SignalingCell SurvivalCell ViabilityCellsCellular FunctionCellular MigrationCellular MotilityCellular PhysiologyCellular ProcessClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCommunicationCommunitiesComplexCrystallizationCytotoxic T-Lymphocyte Protein 4Cytotoxic T-Lymphocyte-Associated Antigen 4Cytotoxic T-Lymphocyte-Associated Protein 4Cytotoxic T-Lymphocyte-Associated Serine Esterase-4DNA mutationDNase-I FootprintingDataDevelopmentDiabetes MellitusDiseaseDisease remissionDisorderENUEducational process of instructingEndocrine PancreasEngineeringEpitopesEthylnitrosoureaEtiologyExclusionFunctional RNAFundingGenesGeneticGenetic ChangeGenetic defectGenetic mutationGenotoxinsGerm LinesHumanIDDMImmuneImmunesIn VitroInduced DNA AlterationInduced MutationInduced Sequence AlterationInsulin CellInsulin Secreting CellInsulin-Dependent Diabetes MellitusIntracellular Communication and SignalingInvestigationIslands of LangerhansIslets of LangerhansIsoformsJuvenile-Onset Diabetes MellitusKetosis-Prone Diabetes MellitusKnock-outKnockoutKnowledgeLeadLocationMapsMass Photometry/Spectrum AnalysisMass SpectrometryMass SpectroscopyMass SpectrumMass Spectrum AnalysesMass Spectrum AnalysisMeasuresMeiosisMethodologyMethodsMiceMice MammalsMicrofilamentsMissense MutationModern ManMolecularMolecular InteractionMolecular Sieve ChromatographyMurineMusMutagensMutant Strains MiceMutationMyofilamentsN-Ethyl-N-nitrosoureaN-ethyl-N-nitroso-ureaN-terminalNH2-terminalNesidioblastsNitrosoethylureaNoncoding RNANontranslated RNAPancreatic IsletsPars endocrina pancreatisPathogenesisPatientsPb elementPedigreePeptidesPhasePhenotypePost-Translational Modification Protein/Amino Acid BiochemistryPost-Translational ModificationsPost-Translational Protein ModificationPost-Translational Protein ProcessingPosttranslational ModificationsPosttranslational Protein ProcessingPreventionProtein AnalysisProtein IsoformsProtein ModificationProtein OverexpressionProteinsProteomicsRecoveryRecreationRemissionSignal PathwaySignal TransductionSignal Transduction SystemsSignalingSize Exclusion ChromatographySplice-Junction MutationSplice-Site MutationSubcellular ProcessSudden-Onset Diabetes MellitusSuppressor MutationsT cell receptor repertoire sequencingT cell receptor sequencingT cell responseT-Cell DepletionT-CellsT-LymphocyteT-cell depletion therapyT-cell receptor repertoireT-lymphocyte depletion therapyT1 DMT1 diabetesT1DT1DMTCR repertoireTCR repertoire sequencingTCR sequencingTCR-seqTCRseqTNF Receptor Family ProteinTNF Receptor SuperfamilyTNF ReceptorsTNFRTeachingTestingTherapeuticThymusThymus GlandThymus ProperThymus Reticuloendothelial SystemTimeTissuesTumor Necrosis Factor ReceptorTumor Necrosis Factor Receptor FamilyTumor Necrosis Factor Receptor SuperfamilyType 1 Diabetes MellitusType 1 diabetesType I Diabetes MellitusUntranslated RNAWorkautoimmune reactivityautoreactivitybiological signal transductioncausationcell motilitycell sortingcell typeconditional knock-outconditional knockoutcytotoxic T-lymphocyte antigen 4developmentaldiabetesdisease causationepigenetic regulationgenetic pedigreegenome mutationgenotoxic agentheavy metal Pbheavy metal leadinsulin dependent diabetesinsulin dependent type 1interestjuvenile diabetesjuvenile diabetes mellitusketosis prone diabetesknockout genemeioticmissense single nucleotide polymorphismmissense single nucleotide variantmissense variantmouse mutantmutantnoncodingnovelpedigree structurephospho-proteomicsphosphoproteomicsprotein complexprotein functionprotein protein interactionprotein purificationresponsesynergismthymus derived lymphocytetranscriptomicstype I diabetestype one diabetesβ-cellβ-cellsβCell
Description preview
PROJECT SUMMARY/ABSTRACT
Project 2 will verify and then study the molecular mechanisms of phenotypes created and genetically solved in
Core B and Core C. We expect to find scores of mutations with modifier effects over the term of funding, but
we will not study all of them mechanistically. Herein we describe the key criteria used in selecting…
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