Spatial multiomic mapping of gene function with CRISPRoff

使用 CRISPRoff 进行基因功能的空间多组图谱

基本信息

  • 批准号:
    10518318
  • 负责人:
  • 金额:
    $ 174.02万
  • 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:
    2022-09-01 至 2027-06-30
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY / ABSTRACT A hallmark goal in human biology is to define the relationship between genes and phenotypes. Mapping the function of every gene in human cells will enable us to begin to define how gene expression programs impart specialized and adaptive human cellular functions required for life. We are especially interested in how transcription factors and epigenetic regulators enact cell type specific gene expression programs to dictate cell function during early development. Elucidating how individual genes function to regulate transcription and thus to program cell phenotypes will transform our understanding of human biology, development and disease. A mechanistic understanding of gene function requires scalable approaches for perturbing gene activity, single cell molecular phenotyping assays and robust models of human multicellular biology. We recently developed CRISPRoff— a programmable epigenetic memory writer consisting of a single dead Cas9 fusion protein that durably and robustly silences gene expression. Unlike CRISPR mutagenesis approaches, CRISPRoff gene silencing effectively programs null alleles at the level of target gene mRNA and protein in polyclonal cell populations without induction of DNA damage or the unpredictability of DNA repair processes. We are proposing to optimize a generalizable multiomic CRISPRoff platform for molecularly phenotyping null alleles at single-cell resolution in multicellular models of human development. We will then use this CRISPRoff platform to create single-cell molecular multiomic maps of nuclear gene function across space and time. Lastly, we will evaluate genetic compensation and paralog functional redundancy in multicellular models. Our proposed research will serve to demonstrate the utility of this multiomics CRISPRoff platform for characterizing null alleles and motivate extending this approach to functionally map null allele phenotypes for all genes encoded by the human genome. The results of the proposed research will serve as a fundamental resource and roadmap for a broad community of biomedical scientists and greatly inform our understanding of gene function in human biology and disease.
项目摘要/摘要

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Luke Gilbert其他文献

Luke Gilbert的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Luke Gilbert', 18)}}的其他基金

Spatial multiomic mapping of gene function with CRISPRoff
使用 CRISPRoff 进行基因功能的空间多组图谱
  • 批准号:
    10693360
  • 财政年份:
    2022
  • 资助金额:
    $ 174.02万
  • 项目类别:
Editing CG and non-CG DNA methylation to identify genomic elements that regulate gene expression
编辑 CG 和非 CG DNA 甲基化以识别调节基因表达的基因组元件
  • 批准号:
    10346389
  • 财政年份:
    2021
  • 资助金额:
    $ 174.02万
  • 项目类别:
Drug target identification using CRISPRi/a screening
使用 CRISPRi/a 筛选识别药物靶点
  • 批准号:
    10006378
  • 财政年份:
    2020
  • 资助金额:
    $ 174.02万
  • 项目类别:
A functional genomics approach to determine the mechanism of cellular response to new anti-cancer drugs
确定细胞对新抗癌药物反应机制的功能基因组学方法
  • 批准号:
    9087854
  • 财政年份:
    2016
  • 资助金额:
    $ 174.02万
  • 项目类别:

相似海外基金

Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
  • 批准号:
    502556
  • 财政年份:
    2024
  • 资助金额:
    $ 174.02万
  • 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
  • 批准号:
    10659303
  • 财政年份:
    2023
  • 资助金额:
    $ 174.02万
  • 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
  • 批准号:
    10674405
  • 财政年份:
    2023
  • 资助金额:
    $ 174.02万
  • 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
  • 批准号:
    10758772
  • 财政年份:
    2023
  • 资助金额:
    $ 174.02万
  • 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
  • 批准号:
    10676499
  • 财政年份:
    2023
  • 资助金额:
    $ 174.02万
  • 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
  • 批准号:
    2748611
  • 财政年份:
    2022
  • 资助金额:
    $ 174.02万
  • 项目类别:
    Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
  • 批准号:
    10532032
  • 财政年份:
    2022
  • 资助金额:
    $ 174.02万
  • 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
  • 批准号:
    22K05630
  • 财政年份:
    2022
  • 资助金额:
    $ 174.02万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
  • 批准号:
    10525070
  • 财政年份:
    2022
  • 资助金额:
    $ 174.02万
  • 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
  • 批准号:
    10689017
  • 财政年份:
    2022
  • 资助金额:
    $ 174.02万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了