Project 2: Identify and enhance LOAD-related signatures in outbred and genetically-engineered marmosets

项目 2:识别并增强近交系和基因工程狨猴中与 LOAD 相关的特征

基本信息

项目摘要

PROJECT SUMMARY PROJECT 2 Determining the early molecular and cellular events in the origins and progression of late-onset Alzheimer’s disease (LOAD) will require an analytical approach that integrates genetic, molecular, in vivo imaging, and behavioral data. Many clinical studies with this goal are currently underway, which increasingly complement genetic data with genome-scale molecular data from biofluids and post-mortem tissues, in vivo imaging data of structure and neuropathology, and detailed cognitive data collected over disease progression. Transforming the outcomes of these studies into targeted therapeutic strategies requires translatable animal model systems, both for understanding the biological underpinnings of disease outcomes and preclinical efficacy testing of candidate treatments. The marmoset is potentially the most promising non-human primate model of LOAD, providing an analytical bridge between human studies and high-capacity cell and rodent model systems. Laboratory marmosets with outbred genetics can potentially provide a range of genotypic and phenotypic variation in relevant clinical outcomes. This standing variation can be augmented by genetically engineering variants at specific risk loci, as we have demonstrated with PSEN1. Phenotypic changes in multi-omic, imaging, cognitive, and cellular outcomes can be rigorously studied in an aging primate with an intermediate lifespan. However, to date there have not been systematic studies of aging marmosets at scale. In this project, we will initiate these systematic studies through integrated analyses of genetics and LOAD-related phenotypes in aging marmosets. We will then rigorously test correspondences between human and marmosets at all biological levels, from genetic to multi-scale models. Our goal is to develop the marmoset into a mature platform for preclinical research, which we will pursue with the following three aims: (1) assess natural genetic variation in outbred marmosets as a model Alzheimer’s disease risk in humans; (2) integrate genetic, genomic, and phenotype data to establish robust statistical models of disease in marmosets; and (3) evaluate disease relevance of models by aligning molecular markers of Alzheimer’s disease in marmosets with human study cohorts. Through this work, we expect to lay the foundations for LOAD-related functional genomics in marmosets, provide an expanded view of the impact of natural genetic variation in laboratory marmosets, prioritize genetic variants to engineer in marmosets, and create the first models of LOAD-related marmoset pathology at multiple scales.
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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Gregory W Carter其他文献

Genetic interactions improve models of quantitative traits
遗传相互作用改进数量性状模型
  • DOI:
    10.1038/ng.3829
  • 发表时间:
    2017-03-30
  • 期刊:
  • 影响因子:
    29.000
  • 作者:
    Anna L Tyler;Gregory W Carter
  • 通讯作者:
    Gregory W Carter

Gregory W Carter的其他文献

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{{ truncateString('Gregory W Carter', 18)}}的其他基金

An Explainable Unified AI Strategy for Efficient and Robust Integrative Analysis of Multi-omics Data from Highly Heterogeneous Multiple Studies
一种可解释的统一人工智能策略,用于对来自高度异质性多项研究的多组学数据进行高效、稳健的综合分析
  • 批准号:
    10729965
  • 财政年份:
    2023
  • 资助金额:
    $ 39.66万
  • 项目类别:
Generation, Characterization, and Validation of Marmoset Models of Alzheimer's Disease
阿尔茨海默病狨猴模型的生成、表征和验证
  • 批准号:
    10494769
  • 财政年份:
    2022
  • 资助金额:
    $ 39.66万
  • 项目类别:
Modeling the Genetic Interaction Between Klotho and APOE Alleles in Alzheimer's Disease
模拟阿尔茨海默病中 Klotho 和 APOE 等位基因之间的遗传相互作用
  • 批准号:
    10524407
  • 财政年份:
    2022
  • 资助金额:
    $ 39.66万
  • 项目类别:
Bioinformatics and Data Integration Core
生物信息学和数据集成核心
  • 批准号:
    10494771
  • 财政年份:
    2022
  • 资助金额:
    $ 39.66万
  • 项目类别:
Generation, Characterization, and Validation of Marmoset Models of Alzheimer's Disease
阿尔茨海默病狨猴模型的生成、表征和验证
  • 批准号:
    10819807
  • 财政年份:
    2022
  • 资助金额:
    $ 39.66万
  • 项目类别:
Open Drug Discovery Center for Alzheimer's Disease
阿尔茨海默病开放药物发现中心
  • 批准号:
    10250427
  • 财政年份:
    2019
  • 资助金额:
    $ 39.66万
  • 项目类别:
Open Drug Discovery Center for Alzheimer's Disease
阿尔茨海默病开放药物发现中心
  • 批准号:
    10017132
  • 财政年份:
    2019
  • 资助金额:
    $ 39.66万
  • 项目类别:
IU/JAX/Pitt MODEL-AD: Deep Phenotyping Proteomics Year 1
IU/JAX/Pitt MODEL-AD:深度表型蛋白质组学第 1 年
  • 批准号:
    10092243
  • 财政年份:
    2016
  • 资助金额:
    $ 39.66万
  • 项目类别:
The IU/JAX Alzheimer's Disease Precision Models Center: Metabolomics
IU/JAX 阿尔茨海默病精密模型中心:代谢组学
  • 批准号:
    9537115
  • 财政年份:
    2016
  • 资助金额:
    $ 39.66万
  • 项目类别:
The IU/JAX Alzheimer's Disease Precision Models Center: Aging
IU/JAX 阿尔茨海默病精密模型中心:衰老
  • 批准号:
    9930786
  • 财政年份:
    2016
  • 资助金额:
    $ 39.66万
  • 项目类别:
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