Genome-wide CRISPR-Cas9 screens in insect cells to characterize insecticidal toxins
在昆虫细胞中进行全基因组 CRISPR-Cas9 筛选以表征杀虫毒素
基本信息
- 批准号:10646295
- 负责人:
- 金额:$ 79.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-15 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:Bacterial ToxinsBacteriophagesCRISPR screenCRISPR/Cas technologyCell LineCell modelCellsCommunicable DiseasesCommunitiesCulicidaeDengueDevelopmentDrosophila genusDrosophila melanogasterFamilyFamily memberFutureGenetic RecombinationGoalsGuide RNAHumanIn VitroInsectaInsecticidesIntegration Host FactorsKnock-outKnowledgeLentivirusLibrariesLife Cycle StagesLyme DiseaseMalariaMammalian CellMediatingMethodsModelingMolecularMucinsNematodaPathogenesisPesticidesPlasmidsProteinsRNA libraryRoleSeriesSiteSmall Interfering RNASpecificitySystemTargeted ToxinsTechnologyToxic effectToxinValidationVirulence FactorsWest NileXenorhabdus luminescensZIKV diseasedesignexperimental studyflygenome wide screengenome-widehuman diseasehuman pathogenin vivoknock-downlentivirally transducedmembermosquitocidalnovelpathogenpathogenic bacteriaprototypereceptorrecombinase-mediated cassette exchangesuccesstooltransmission processvector
项目摘要
Project Summary
Genome-wide screens using CRISPR-Cas9 technology have revolutionized studies of
host-pathogen interactions, leading to identification of many key host cellular factors required for
the actions of human pathogens and bacterial toxins. However, this powerful approach has yet to
be utilized in insect cells to uncover host factors required for insect-borne pathogens, which are
responsible for a long list of infectious diseases such as malaria, Dengue, West Nile, Zika, and
Lyme diseases. This is largely due to a technical barrier: the inability to efficiently deliver genome-
wide guide RNA library into insect cells. We recently overcame this barrier and developed a
genome-wide CRISPR-Cas9 screening method in cultured Drosophila cells. Using this method,
and by leveraging the expertise of Dr. Norbert Perrimon’s lab in insect models and of Dr. Min
Dong’s lab in bacterial toxins, we carried out extensive preliminary studies, leading to the
identification of a potential insect receptor for a member of the major bacterial toxin family known
as Tc toxins, demonstrating the power and feasibility of our unbiased genome-wide screen
approach. Building on these successes, in Aim 1 we will focus on further development and
validation of genome-wide screens with major Tc toxin family members to establish a mechanistic
understanding of toxin-receptor interactions and their role in pathogenesis in vitro and in vivo. We
further propose to expand our approach to establish the first genome-wide CRISPR-Cas9
screening method and tools in mosquito cells in Aim2, and then utilize this approach to identify
key host factors for two novel bacterial toxins that showed selective toxicity on mosquito but not
Drosophila cells. The success of our proposal will uncover receptors and key host cellular factors
for important bacterial toxins and establish generalizable methods and essential tools for
investigating pathogens and toxins at genome-wide scale in insect cells relevant to transmitting
human infectious diseases.
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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Min Dong其他文献
Min Dong的其他文献
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{{ truncateString('Min Dong', 18)}}的其他基金
Genome-wide CRISPR-Cas9 screens in insect cells to characterize insecticidal toxins
在昆虫细胞中进行全基因组 CRISPR-Cas9 筛选以表征杀虫毒素
- 批准号:
10873497 - 财政年份:2022
- 资助金额:
$ 79.49万 - 项目类别:
Developmental Pharmacology of Hydroxyurea Across the Age Span for the Treatment of Sickle Cell Anemia
不同年龄段羟基脲治疗镰状细胞性贫血的发育药理学
- 批准号:
10382052 - 财政年份:2022
- 资助金额:
$ 79.49万 - 项目类别:
Genome-wide CRISPR-Cas9 screens in insect cells to characterize insecticidal toxins
在昆虫细胞中进行全基因组 CRISPR-Cas9 筛选以表征杀虫毒素
- 批准号:
10502624 - 财政年份:2022
- 资助金额:
$ 79.49万 - 项目类别:
Developmental Pharmacology of Hydroxyurea Across the Age Span for the Treatment of Sickle Cell Anemia
不同年龄段羟基脲治疗镰状细胞性贫血的发育药理学
- 批准号:
10551233 - 财政年份:2022
- 资助金额:
$ 79.49万 - 项目类别:
Model-Informed Evaluation of Hydroxyurea Exposure in Special Populations
特殊人群羟基脲暴露的模型知情评估
- 批准号:
10653016 - 财政年份:2022
- 资助金额:
$ 79.49万 - 项目类别:
Model-Informed Evaluation of Hydroxyurea Exposure in Special Populations
特殊人群羟基脲暴露的模型知情评估
- 批准号:
10427738 - 财政年份:2022
- 资助金额:
$ 79.49万 - 项目类别:
Targeted delivery of therapeutics into motor neurons for post-exposure treatment of botulism
将治疗药物靶向输送至运动神经元,用于肉毒杆菌中毒的暴露后治疗
- 批准号:
10453725 - 财政年份:2021
- 资助金额:
$ 79.49万 - 项目类别:
Targeted delivery of therapeutics into motor neurons for post-exposure treatment of botulism
将治疗药物靶向输送至运动神经元,用于肉毒杆菌中毒的暴露后治疗
- 批准号:
10210524 - 财政年份:2021
- 资助金额:
$ 79.49万 - 项目类别:
Targeted Delivery of Therapeutics into Motor Neurons for Post-exposure Treatment of Botulism
将治疗药物靶向输送至运动神经元,用于肉毒杆菌中毒的暴露后治疗
- 批准号:
10653914 - 财政年份:2021
- 资助金额:
$ 79.49万 - 项目类别:
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