Exploring Mechanisms in Retinal Development/Homeostasis, Retinal Immune Surveillance and Diabetic Retinopathy Using Forward Genetics

利用正向遗传学探索视网膜发育/稳态、视网膜免疫监视和糖尿病视网膜病变的机制

基本信息

  • 批准号:
    10316653
  • 负责人:
  • 金额:
    $ 45.1万
  • 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:
    2021-09-30 至 2026-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary Defects in the carefully orchestrated processes of retinal development, homeostasis and retinal immune surveillance lead or contribute to a wide range of diseases. It is now clear that genetics not only play a role in these processes but may also modulate diabetic retinopathy. Our short-term goal is to identify and characterize gene/protein defects and molecular pathways that lead to abnormal retinal development/homeostasis, altered retinal immune surveillance and modulation of diabetic retinopathy. The long-term goal is to leverage our research discoveries to understand retinal disease processes, and to identify novel therapeutic opportunities. We propose that a high-throughput and unbiased strategy provides an ideal approach to discovery of gene/phenotype associations in this setting. In collaboration with Nobel laureate Bruce Beutler, we will employ a robust state-of-the-science and unbiased forward genetics approach, in which thousands of new random mutations are generated and mice demonstrating retinal anomalies are identified by screening using fundus photographs and OCT. Our approach has significant advantages compared to other existing protocols. Most importantly, ours is the first and only protocol in which all mice have been pre-genotyped at all mutant loci. In addition, the large scale of our system and the large pedigree size will also add to the discovery power. Together, these advantages will allow us to identify and pursue novel gene/phenotype associations related to retinal development, homeostasis and disease. We have identified over 43 gene-phenotype associations after covering just 8% of the mouse genome. Of these, 12 genes have weak associations to the retina in the literature, and another 20 genes have not been reported in association to the retina. This is strong evidence that expanding our screening to include the remaining 92% of the mouse genome will yield many more gene-phenotype associations related to retina development, homeostasis and immune surveillance. Of note, our proposal starts by selecting a few of the most promising genes we have already identified for further study. We will harness the power of CRISPR/Cas9 gene editing, single cell RNA sequencing, co-immunoprecipitation experiments with highly sensitive mass spectrometry and proteomics analysis, our recently published light injury model and other techniques to explore the mechanisms of these associations. We will also apply the streptozotocin model of diabetic retinopathy to our OCT retinal imaging pipeline to identify genes that can modulate early diabetic retinopathy. This proposed research will advance our knowledge of retinal health and disease, and we anticipate that it will lead to the identification of new therapeutic avenues.
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)

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 }}

Rafael Ufret-Vincenty其他文献

Rafael Ufret-Vincenty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('Rafael Ufret-Vincenty', 18)}}的其他基金

Exploring Mechanisms in Retinal Development/Homeostasis - Admin. Supplement
探索视网膜发育/稳态的机制 - 管理。
  • 批准号:
    10636145
  • 财政年份:
    2021
  • 资助金额:
    $ 45.1万
  • 项目类别:
Exploring Mechanisms in Retinal Development/Homeostasis, Retinal Immune Surveillance and Diabetic Retinopathy Using Forward Genetics
利用正向遗传学探索视网膜发育/稳态、视网膜免疫监视和糖尿病视网膜病变的机制
  • 批准号:
    10672979
  • 财政年份:
    2021
  • 资助金额:
    $ 45.1万
  • 项目类别:
Role of complement factor H and immunity in AMD: a novel transgenic model
补体因子 H 和免疫在 AMD 中的作用:一种新型转基因模型
  • 批准号:
    8345535
  • 财政年份:
    2012
  • 资助金额:
    $ 45.1万
  • 项目类别:
Role of complement factor H and immunity in AMD: a novel transgenic model
补体因子 H 和免疫在 AMD 中的作用:一种新型转基因模型
  • 批准号:
    8546385
  • 财政年份:
    2012
  • 资助金额:
    $ 45.1万
  • 项目类别:
Role of complement factor H and immunity in AMD: a novel transgenic model
补体因子 H 和免疫在 AMD 中的作用:一种新型转基因模型
  • 批准号:
    8708875
  • 财政年份:
    2012
  • 资助金额:
    $ 45.1万
  • 项目类别:

相似海外基金

Variability of Brain Reorganization in Blindness
失明时大脑重组的变异性
  • 批准号:
    10562129
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
Beyond the Visual: Blindness and Expanded Sculpture
超越视觉:失明与扩展的雕塑
  • 批准号:
    AH/Y005856/1
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
    Research Grant
Innovative therapeutic strategies to support elimination of river blindness
支持消除河盲症的创新治疗策略
  • 批准号:
    10754120
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
Anatomical, neural, and computational constraints on sensory cross-modal plasticity following early blindness
早期失明后感觉跨模态可塑性的解剖学、神经学和计算限制
  • 批准号:
    10570400
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
Follow on to: Preventing avoidable blindness through smart home-monitoring of vision
继续:通过智能家居视力监测预防可避免的失明
  • 批准号:
    ES/Y001346/1
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
    Research Grant
Establishment of preventive methods for blindness due to pathologic myopia by targeting CCDC102B
以CCDC102B为靶点建立病理性近视致盲预防方法
  • 批准号:
    23K09009
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mechanisms of neural compensation in the retina and dysfunction in congenital stationary night blindness
先天性静止性夜盲症视网膜神经代偿机制及功能障碍
  • 批准号:
    10678730
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
NSF Convergence Accelerator Track H: Phase II Smart Wearables for Expanding Workplace Access for People with Blindness and Low Vision
NSF 融合加速器轨道 H:第二阶段智能可穿戴设备,扩大失明和低视力人士的工作场所使用范围
  • 批准号:
    2345139
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
    Cooperative Agreement
3D bioprinting of regenerative, corneal cell-laden inks to treat corneal blindness
3D 生物打印充满角膜细胞的再生墨水来治疗角膜失明
  • 批准号:
    10606474
  • 财政年份:
    2023
  • 资助金额:
    $ 45.1万
  • 项目类别:
From 'plant blindness' to 'bug blindness': disseminating an evidence-based pedagogy for plants and refining methodologies in attitudinal research
从“植物盲”到“虫盲”:传播植物循证教育学并完善态度研究方法
  • 批准号:
    ES/X007324/1
  • 财政年份:
    2022
  • 资助金额:
    $ 45.1万
  • 项目类别:
    Fellowship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了