Genome engineering in the nematode C. elegans
线虫的基因组工程。 elegans
基本信息
- 批准号:10565428
- 负责人:
- 金额:$ 31.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-02-01 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAmino Acid MotifsAnimalsBiochemicalBiological AssayBiological ModelsBiologyC. elegans genomeCaenorhabditis elegansCellsClustered Regularly Interspaced Short Palindromic RepeatsCodeCollectionCommunitiesComputer softwareDNADNA IntegrationDNA cassetteDiseaseEngineeringEventExcisionFreezingFutureGene ModifiedGene TargetingGenerationsGenesGeneticGenetic DiseasesGenetic RecombinationGenomeGenome engineeringGenomicsGoalsGuide RNAHandHumanHuman GeneticsIndividualInjectionsLaboratoriesLibrariesLocationMeasuresMethodsModelingModificationMolecularMolecular BiologyMutateNematodaOligonucleotidesOrganismPhenotypeProcessProteinsProteomeRandom AllocationReactionReagentResearch PersonnelSeriesSignal PathwaySiteSoftware ToolsSpeedStructureTestingTimeTransgenesWorkWritingcell typecostcost effectivedesignexperienceexperimental studygene functiongenetic manipulationgenome editinggenomic toolsimprovedmodel organismnovelrapid techniquerecombinaserecombinase-mediated cassette exchangerepairedsoftware developmenttool
项目摘要
Project Summary
CRISPR offers the promise of total control over genes in model organisms, such as the nematode
C. elegans. To make this a reality, we need functional tags on all proteins that we can use as handles to
influence the biology of any cell. However, each individual edit requires unique reagents and takes experienced
worm geneticists 6 weeks or more to create. To edit many genes with diverse tags one gene at a time is just
not practical. The goals of this project are to make CRISPR genome modifications simple, inexpensive and
with increased throughput. We propose a series of multiplexed genome engineering methods that will
accelerate gene tagging in C. elegans 10- to 100-fold. First, we propose to optimize cassette exchange
methods using diverse recombinases that will allow geneticists to alter one gene with many diverse tags.
Second, we propose to develop a multiplexed CRISPR strategy that will allow groups to modify many genes
within a single editing experiment. Third, we will develop software and reagent libraries required to modify all
genes in the genome.
• Aim 1. One gene: recombinase-mediated cassette exchange. We will characterize the germline activity
of a diverse set of recombinases and develop cassette exchange methods for rapidly integrating transgenes
or tags anywhere in the genome.
• Aim 2. Many genes: multiplex CRISPR. Current methods require a unique injection cocktail for each
unique gene modification. We will develop a multiplex CRISPR strategy in which the reagents for tagging many
unique genes are injected simultaneously to generate many edited worm strains, each with a single edited
target.
• Aim 3. All genes: software and molecular reagents. To tag the proteome, reagents cannot be efficiently
designed one-at-a-time, by hand. We will write software that identifies optimal tagging locations and designs
the required reagents, and we will build build a cost-effective pooled molecular workflow to build genome editing
reagents.
C. elegans shares most of the genes mutated in human genetic diseases; as a simple, compact and rapidly
developing animal, it is an attractive platform to study these genes. In the future, the genome engineering
pipelines developed here could be used to insert a swappable tagging site in every protein-coding gene in the
C. elegans genome, making it possible to easily add any tag to any gene. Such a strain collection would be a
boon for cell biologists and geneticists, enabling new inroads in studying how cells work and how to fix them
when disease processes cause them to malfunction.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ERIK M JORGENSEN其他文献
ERIK M JORGENSEN的其他文献
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{{ truncateString('ERIK M JORGENSEN', 18)}}的其他基金
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Grant-in-Aid for General Scientific Research (C)














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