HIGH-THROUGHPUT IN VIVO SUBCELLULAR-RESOLUTION VERTEBRATE SCREENING PLATFORM

高通量体内亚细胞分辨率脊椎动物筛选平台

基本信息

项目摘要

DESCRIPTION (provided by applicant): The ability to study whole organisms makes it possible to study complex in vivo processes that cannot be replicated in vitro such as organ development, liver, pancreas, heart, and neuronal regeneration, cancer metastasis, neural degeneration, infectious disease progression, pathogenesis, cardiovascular, immune, endocrine, and nervous system functions. Cells are not transformed and are in their normal physiological environment of cell-cell, extracellular matrix, and other interactions. Microarray studies and in vitro screens using cell lines and millions of combinatorially synthesized compounds have generated thousands of possible genetic targets and drug candidates. Identification of specificity, potency, toxicity, and biodistribution of pharmaceuticals as well as functions of thousands genes on entire organs like kidney, liver, heart, and brain cannot be done in vitro, and require use of in vivo animal models. Currently, there is significant gap between the throughput and capabilities of in vitro and in vivo assays on vertebrates. As a result, during early stages of drug screening and development, pharmaceuticals cannot be tested in vivo. Failure of tests on animals at later stages of development not only costs dearly, but also slows progress significantly. Yet, high-throughput testing of gene functions and compounds using in vivo vertebrate animal models has so far been significantly limited due to the absence of key technologies. Here, we propose a highly transformative technology that will allow, for the first time, large- scale in vivo genetic and chemical screens at cellular resolution on complex organs of vertebrates such as heart, liver, kidney, pancreas, vision, immune system, and central nervous system. This technology can impact a broad spectrum of fields ranging from neurobiology to regenerative biology, and cancer biology. The proposed high-speed whole-animal manipulation, orientation, immobilization, imaging, microsurgery, and injection platform will enable a dramatic increase in the throughput and complexity with which in vivo assays can be performed (~5-10 seconds per animal depending on the observed phenotype and manipulation complexity instead of the 10-30 minutes it currently takes). Our proposal is highly relevant to NIH's roadmap goals as it will allow systematic and unbiased genome-wide vertebrate studies to dramatically accelerate both fundamental and translational research in identification of gene functions as well as in discovery of drug leads. To demonstrate system capabilities, we will perform the first large-scale in vivo chemical screen for regenerating micro-surgically injured spinal-cord fibers. PUBLIC HEALTH RELEVANCE: This project will develop a highly transformative technology that will allow, for the first time, large-scale in vivo genetic and chemical screens at cellular resolution on complex organs of vertebrates such as heart, liver, kidney, pancreas, vision, immune system, and central nervous system, for identification of drug leads for various human diseases, disorders, and injuries. To demonstrate the capabilities of this technology, we will perform the first large-scale in vivo chemical screen for regenerating microsurgically injured spinal cord fibers.
描述(由申请人提供):研究整个生物体的能力使得研究无法在体外复制的复杂体内过程成为可能,例如器官发育、肝脏、胰腺、心脏和神经元再生、癌症转移、神经变性、传染病进展、发病机制、心血管、免疫、内分泌和神经系统功能。细胞没有发生转化,处于细胞间、细胞外基质和其他相互作用的正常生理环境中。使用细胞系和数百万种组合合成化合物的微阵列研究和体外筛选已经产生了数千种可能的遗传靶标和候选药物。药物的特异性、效力、毒性和生物分布以及肾脏、肝脏、心脏和大脑等整个器官上数千个基因的功能的鉴定无法在体外完成,需要使用体内动物模型。目前,脊椎动物体外和体内检测的通量和能力之间存在显着差距。因此,在药物筛选和开发的早期阶段,药物无法进行体内测试。在发育后期对动物进行的测试失败不仅代价高昂,而且会显着减缓进展。然而,由于缺乏关键技术,迄今为止,利用体内脊椎动物模型对基因功能和化合物进行高通量测试仍受到很大限制。 在这里,我们提出了一种高度变革的技术,该技术将首次允许对脊椎动物的复杂器官(如心脏、肝脏、肾脏、胰腺、视觉、免疫系统和中枢神经系统)进行细胞分辨率的大规模体内遗传和化学筛选。这项技术可以影响从神经生物学到再生生物学和癌症生物学等广泛领域。所提出的高速全动物操作、定向、固定、成像、显微手术和注射平台将显着提高体内检测的吞吐量和复杂性(每只动物约 5-10 秒,具体取决于观察到的表型和操作复杂性,而不是目前需要的 10-30 分钟)。我们的提案与 NIH 的路线图目标高度相关,因为它将允许系统且公正的全基因组脊椎动物研究显着加速基因功能识别以及药物先导化合物发现方面的基础研究和转化研究。为了展示系统功能,我们将进行首次大规模体内化学筛选,以再生显微手术损伤的脊髓纤维。 公共健康相关性:该项目将开发一种高度变革性的技术,首次能够以细胞分辨率对脊椎动物的复杂器官(如心脏、肝脏、肾脏、胰腺、视觉、免疫系统和中枢神经系统)进行大规模体内遗传和化学筛选,以识别各种人类疾病、病症和损伤的药物先导物。为了展示这项技术的能力,我们将进行首次大规模体内化学筛选,以再生显微手术损伤的脊髓纤维。

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 }}

Mehmet Fatih Yanik其他文献

Functional regeneration after laser axotomy
激光轴突切断后的功能性再生
  • DOI:
    10.1038/432822a
  • 发表时间:
    2004-12-15
  • 期刊:
  • 影响因子:
    48.500
  • 作者:
    Mehmet Fatih Yanik;Hulusi Cinar;Hediye Nese Cinar;Andrew D. Chisholm;Yishi Jin;Adela Ben-Yakar
  • 通讯作者:
    Adela Ben-Yakar
Verfahren zur zelltransfektion mit nukleinsäuren
核转移的影响
  • DOI:
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Mehmet Fatih Yanik;Matthew Angel
  • 通讯作者:
    Matthew Angel
Deep-learning-based identification, tracking, pose estimation and behaviour classification of interacting primates and mice in complex environments
基于深度学习的复杂环境中相互作用的灵长类动物和小鼠的识别、跟踪、姿势估计和行为分类
  • DOI:
    10.1038/s42256-022-00477-5
  • 发表时间:
    2022-04-21
  • 期刊:
  • 影响因子:
    23.900
  • 作者:
    Markus Marks;Qiuhan Jin;Oliver Sturman;Lukas von Ziegler;Sepp Kollmorgen;Wolfger von der Behrens;Valerio Mante;Johannes Bohacek;Mehmet Fatih Yanik
  • 通讯作者:
    Mehmet Fatih Yanik

Mehmet Fatih Yanik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('Mehmet Fatih Yanik', 18)}}的其他基金

Generating transplantable neurons by in vivo combinatorial screening of transcrip
通过体内转录组合筛选产生可移植神经元
  • 批准号:
    8337690
  • 财政年份:
    2011
  • 资助金额:
    $ 40.51万
  • 项目类别:
Generating transplantable neurons by in vivo combinatorial screening of transcrip
通过体内转录组合筛选产生可移植神经元
  • 批准号:
    8142682
  • 财政年份:
    2011
  • 资助金额:
    $ 40.51万
  • 项目类别:
Generating transplantable neurons by in vivo combinatorial screening of transcrip
通过体内转录组合筛选产生可移植神经元
  • 批准号:
    8912552
  • 财政年份:
    2011
  • 资助金额:
    $ 40.51万
  • 项目类别:
Generating transplantable neurons by in vivo combinatorial screening of transcrip
通过体内转录组合筛选产生可移植神经元
  • 批准号:
    8508325
  • 财政年份:
    2011
  • 资助金额:
    $ 40.51万
  • 项目类别:
Generating transplantable neurons by in vivo combinatorial screening of transcrip
通过体内转录组合筛选产生可移植神经元
  • 批准号:
    8712586
  • 财政年份:
    2011
  • 资助金额:
    $ 40.51万
  • 项目类别:
HIGH-THROUGHPUT IN VIVO SUBCELLULAR-RESOLUTION VERTEBRATE SCREENING PLATFORM
高通量体内亚细胞分辨率脊椎动物筛选平台
  • 批准号:
    8268464
  • 财政年份:
    2010
  • 资助金额:
    $ 40.51万
  • 项目类别:
HIGH-THROUGHPUT IN VIVO SUBCELLULAR-RESOLUTION VERTEBRATE SCREENING PLATFORM
高通量体内亚细胞分辨率脊椎动物筛选平台
  • 批准号:
    8660716
  • 财政年份:
    2010
  • 资助金额:
    $ 40.51万
  • 项目类别:
HIGH-THROUGHPUT IN VIVO SUBCELLULAR-RESOLUTION VERTEBRATE SCREENING PLATFORM
高通量体内亚细胞分辨率脊椎动物筛选平台
  • 批准号:
    8477325
  • 财政年份:
    2010
  • 资助金额:
    $ 40.51万
  • 项目类别:
HIGH-THROUGHPUT IN VIVO SUBCELLULAR-RESOLUTION VERTEBRATE SCREENING PLATFORM
高通量体内亚细胞分辨率脊椎动物筛选平台
  • 批准号:
    8150903
  • 财政年份:
    2010
  • 资助金额:
    $ 40.51万
  • 项目类别:
High-throughput single-cell-resolution genetic and pharmacological screens using
高通量单细胞分辨率遗传和药理学筛选
  • 批准号:
    8053299
  • 财政年份:
    2009
  • 资助金额:
    $ 40.51万
  • 项目类别:

相似海外基金

The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
  • 批准号:
    EP/Z000920/1
  • 财政年份:
    2025
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
  • 批准号:
    FT230100276
  • 财政年份:
    2024
  • 资助金额:
    $ 40.51万
  • 项目类别:
    ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
  • 批准号:
    MR/X024261/1
  • 财政年份:
    2024
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
  • 批准号:
    DE240100388
  • 财政年份:
    2024
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
  • 批准号:
    2232190
  • 财政年份:
    2023
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
  • 批准号:
    2337595
  • 财政年份:
    2023
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
  • 批准号:
    23K17514
  • 财政年份:
    2023
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
  • 批准号:
    23KK0126
  • 财政年份:
    2023
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
  • 批准号:
    2842926
  • 财政年份:
    2023
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
  • 批准号:
    NC/X001644/1
  • 财政年份:
    2023
  • 资助金额:
    $ 40.51万
  • 项目类别:
    Training Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了