A Comprehensive Resource for Manipulating the Drosophila Genome

操纵果蝇基因组的综合资源

基本信息

  • 批准号:
    10437006
  • 负责人:
  • 金额:
    $ 80.21万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The Drosophila Gene Disruption Project (GDP), since its foundation in 2000, has produced a large, publicly available library of individual, sequence-mapped transposable element (TE) insertions that have become an essential resource for fly research. Generating and sequencing 180,000 TEs allowed the most useful ~22,000 (located in/near 13,000 genes) to be selected and deposited in the Bloomington Drosophila Stock Center. More than 750,000 GDP cultures have been distributed to thousands of labs nationally and internationally, facilitating the analysis of thousands of genes. The features of the TEs developed by the GDP, particularly the MiMIC TE, greatly enhance their value as they allow characterization of gene expression, protein distribution, tissue specific knock down, isolation of interacting proteins, assessment of the function of homologues of other species and other sophisticated, state-of-the-art manipulations. The flexibility to swap any DNA cassette into existing MiMIC TE sites provides a genetic toolkit that is unrivaled, greatly advancing the field of functional genomics and impacting our understanding of gene function across species. During the proposed budget period, the GDP will provide tools to analyze gene function that will constitute a new resource not only to tackle basic biological questions but also medical questions aiding with the discovery and study of new human diseases and their underlying mechanisms. A critical prerequisite for modeling disease in Drosophila is the ability to express each of the 9,000 evolutionarily conserved human genes in the endogenous expression pattern of their fly ortholog. This can currently be achieved by using MiMIC and the SA-T2A-GAL4-polyA cassette (T2A-GAL4). When inserted in introns between two coding exons, this cassette is highly mutagenic and produces a GAL4 that can be used to drive the UAS-cDNA of a fly or human homolog, frequently rescuing the mutant phenotype and allowing disease modeling. Here, we propose to expand the tagging of most genes that can be tagged with this approach. We have also developed a new strategy to permit replacement of all genes that do not have suitable introns for T2A-GAL4 integration, which constitute about 45% of all fly genes. This method exchanges the gene's entire coding regions with a Kozak consensus sequence followed by GAL4. We propose to target 2,300 currently untagged Drosophila genes using these two strategies depending on the structure of the locus and the nature of the cassette to be inserted. The vast majority of the genes will be tagged with GAL4 because it permits numerous elegant applications. The resulting lines will be characterized genetically and molecularly and the expression pattern of the genes will be documented in third instar larval brains. The generation and distribution of these reagents is highly appreciated by the Drosophila community as shown by the many letters of support from leaders in the fly community.
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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HUGO J BELLEN其他文献

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{{ truncateString('HUGO J BELLEN', 18)}}的其他基金

Center for functional analysis of human UDN gene homologs in Drosophila and zebrafish
果蝇和斑马鱼人类UDN基因同源物功能分析中心
  • 批准号:
    10600181
  • 财政年份:
    2022
  • 资助金额:
    $ 80.21万
  • 项目类别:
Genomic medicine and gene function implementation for an underserved population
针对服务不足人群的基因组医学和基因功能实施
  • 批准号:
    10450159
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
Functional Genomic Dissection of Alzheimer's Disease in Humans and Drosophila Models
人类和果蝇模型中阿尔茨海默病的功能基因组解剖
  • 批准号:
    10681445
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
IMPACTS OF GLIAL LIPID DROPLETS ON OXIDATIVE STRESS AND NEURODEGENERATION IN ALZHEIMER'S DISEASE
胶质脂滴对阿尔茨海默病氧化应激和神经变性的影响
  • 批准号:
    10804252
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
Genomic medicine and gene function implementation for an underserved population
针对服务不足人群的基因组医学和基因功能实施
  • 批准号:
    10640103
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
IMPACTS OF GLIAL LIPID DROPLETS ON OXIDATIVE STRESS AND NEURODEGENERATION IN ALZHEIMER'S DISEASE
胶质脂滴对阿尔茨海默病氧化应激和神经变性的影响
  • 批准号:
    10276761
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
A Comprehensive Resource for Manipulating the Drosophila Genome
操纵果蝇基因组的综合资源
  • 批准号:
    10267895
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
IMPACTS OF GLIAL LIPID DROPLETS ON OXIDATIVE STRESS AND NEURODEGENERATION IN ALZHEIMER'S DISEASE
胶质脂滴对阿尔茨海默病氧化应激和神经变性的影响
  • 批准号:
    10640936
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
IMPACTS OF GLIAL LIPID DROPLETS ON OXIDATIVE STRESS AND NEURODEGENERATION IN ALZHEIMER'S DISEASE
胶质脂滴对阿尔茨海默病氧化应激和神经变性的影响
  • 批准号:
    10473724
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:
Genomic medicine and gene function implementation for an underserved population
针对服务不足人群的基因组医学和基因功能实施
  • 批准号:
    10227469
  • 财政年份:
    2021
  • 资助金额:
    $ 80.21万
  • 项目类别:

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