Novel Gene Control of Lymphoid Tissue Development
淋巴组织发育的新基因控制
基本信息
- 批准号:7046131
- 负责人:
- 金额:$ 8.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-04-01 至 2010-03-31
- 项目状态:已结题
- 来源:
- 关键词:B lymphocytePeyer&aposs patchesdevelopmental geneticsdevelopmental immunologyembryo /fetus tissue transplantationflow cytometrygel mobility shift assaygene expressiongene mutationgenetic regulationgenetically modified animalsimmune responseimmunocytochemistryimmunogeneticsin situ hybridizationlaboratory mouselymphatic tissuemicroarray technologynuclear factor kappa betanucleic acid sequencepolymerase chain reaction
项目摘要
DESCRIPTION (provided by applicant): The candidate: I am a veterinarian with a clinical background, completing a Ph.D. in biochemistry and molecular biology and a 4-year postdoctoral fellowship at The Jackson Laboratory. My primary interests are in genetics and immunology, with a long-term goal of becoming an independent research scientist. The unique opportunity offered by the K08 program to perform independent research of my own design with the guidance of experienced mentors at one of the world's premier biomedical institutions creates an ideal transition period in which to perform the valuable research described in this application and to gain the experience essential to scientific autonomy. The objective of this proposal is to identify the cellular and molecular basis of the chronic proliferative dermatitis (cpdm) mutation and to determine the role of the wildt ype allele in normal lymphoid development and function. Affected mice possess normal numbers of peripheral lymph nodes, but have multiple immunologic abnormalities including absent Peyer's patches, disorganized lymphoid architecture, diminished B cell maturation and class switching, and multi-organ inflamation. Peyer's patches are a key component of the gut-associated lymphoid tissue, which contributes to production of secretory IgA by B cells and provides the chief defense against oral pathogen invasion. IgA deficiency is a common form of immune deficiency in humans, and has also been implicated in autoimmunity. One of the goals of this research is to fill existing gaps in our current understanding of the developmental biology of Peyer's patches. Hypothesis: The gene containing the cpdm mutation is a stromal target downstream of the NF-KB transcription factor RelB/P52, and is critical for development of Peyer's patches and organization of lymphoid tissues. This gene also contributes to normal maturation and function of B cells. Specific aims: (1) Identify the gene containing the cpdm mutation, using quantitative RTPCR and direct sequencing of 21 remaining candidate genes in a 372-Kb interval, none of which has been previously implicated in lymphoid development, maintenance or function. (2) Evaluate mechanisms by which the cpdm locus contributes to Peyer's patch development, normal lymphoid organization and B cell immune responses.
Significance: These studies will provide new insight into the unique developmental requirements for Peyer's patches and better understanding of the relationship between lymphoid organization and function.
简介(申请人提供):候选人:我是一名具有临床背景的兽医,正在攻读生物化学和分子生物学博士学位,并在杰克逊实验室进行为期四年的博士后研究。我的主要兴趣是遗传学和免疫学,长期目标是成为一名独立的研究科学家。K08项目提供了独特的机会,让我在世界一流的生物医学机构之一的经验丰富的导师的指导下进行自己设计的独立研究,这为我提供了一个理想的过渡时期,在这个过渡时期,我可以进行本申请中描述的有价值的研究,并获得科学自主所必需的经验。本提案的目的是确定慢性增生性皮炎(cpdm)突变的细胞和分子基础,并确定野生型等位基因在正常淋巴细胞发育和功能中的作用。受影响的小鼠拥有正常数量的周围淋巴结,但有多种免疫异常,包括Peyer's patches缺失,淋巴样结构紊乱,B细胞成熟和类别转换减少,以及多器官炎症。Peyer’s patch是肠道相关淋巴组织的关键组成部分,它有助于B细胞分泌IgA的产生,并提供抵抗口腔病原体入侵的主要防御。IgA缺乏症是人类免疫缺陷的一种常见形式,也与自身免疫有关。这项研究的目标之一是填补我们目前对Peyer斑块发育生物学理解的现有空白。假设:含有cpdm突变的基因是NF-KB转录因子RelB/P52下游的基质靶点,对Peyer’s patches的发育和淋巴组织的组织至关重要。该基因也有助于B细胞的正常成熟和功能。具体目标:(1)鉴定含有cpdm突变的基因,使用定量RTPCR和直接测序剩余的21个候选基因(372-Kb间隔),这些基因之前都没有涉及淋巴细胞的发育、维持或功能。(2)评估cpdm基因座参与Peyer’s patch发育、正常淋巴组织和B细胞免疫应答的机制。
项目成果
期刊论文数量(0)
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Rosemarie E Seymour其他文献
Rosemarie E Seymour的其他文献
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{{ truncateString('Rosemarie E Seymour', 18)}}的其他基金
Novel Gene Control of Lymphoid Tissue Development
淋巴组织发育的新基因控制
- 批准号:
7595763 - 财政年份:2005
- 资助金额:
$ 8.63万 - 项目类别:
Novel Gene Control of Lymphoid Tissue Development
淋巴组织发育的新基因控制
- 批准号:
7214665 - 财政年份:2005
- 资助金额:
$ 8.63万 - 项目类别:
Novel Gene Control of Lymphoid Tissue Development
淋巴组织发育的新基因控制
- 批准号:
6922987 - 财政年份:2005
- 资助金额:
$ 8.63万 - 项目类别:
Novel Gene Control of Lymphoid Tissue Development
淋巴组织发育的新基因控制
- 批准号:
7391306 - 财政年份:2005
- 资助金额:
$ 8.63万 - 项目类别: