CHARACTERIZATION OF LYMPHOCYTE SIGNAL TRANSDUCTION IN RESPONSE TO MERCURY EXPOSU

响应汞暴露的淋巴细胞信号转导的特征

• 批准号: 8359815
• 负责人: Benjamin Rowley
• 金额: $ 1.6万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359815
• 关键词: Activated B-Lymphocyte; Antibodies; Arkansas; Autoantibodies; Autoimmune Process; B-Lymphocytes; Biomedical Research; Cell Culture Techniques; Cell Line; Cells; Chronic; Collaborations; DNA; Data; Development; Disease; Dose; Exposure to; Funding; Goals; Grant; Health; Immune system; Lead; Longevity; Lupus; Lymphocyte; Mercury; Mercury Compounds; National Center for Research Resources; Organism; Principal Investigator; Production; Publishing; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Scleroderma; Signal Transduction; Signal Transduction Pathway; Source; Staging; Syndrome; T-Lymphocyte; Training; United States National Institutes of Health; Universities; Work; career development; cost; novel; programs; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Environmental and dietary exposures to small amounts of mercury compounds occur throughout an organism's lifespan. While the negative health effects of large-scale exposures have been well-studied, it has been only recently that researchers have begun to examine the effects of lower, chronic exposures. These exposures induce perturbations of the immune system, resulting in the induction of anti-self autoantibody production by inappropriately activated B lymphocytes. This autoantibody production can progress to an autoimmune syndrome, most notably disorders similar to lupus (with anti-DNA autoantibodies) and scleroderma (with anti-DNA and anti-nucleolar antibodies). While much work has been performed on the altered function of mercury-treated cells, little has been examined in relation to the signal transduction pathways in lymphocytes. The proposed work will characterize changes in signal transduction pathway utilization in mercury-treated B lymphocyte cell culture lines upon activation. This work is novel to this field, as the main focus of mercury-exposure research has centered on either higher doses of mercury, or cells other than lymphocytes. Furthermore, this work will be used to expand the project in subsequent stages into primary B lymphocytes and T lymphocyte cell culture lineages. It is expected that this research project will provide preliminary data necessary to bring similar, but expanded studies to the University of Central Arkansas. A secondary goal is to fine-tune this project to include and train undergraduates/graduates. Therefore, this project is vital to the long term development of my research program at UCA. This summer project will lead to identified additional proposals to seek long term federal-level support. The ultimate goal is to pursue a broad and comprehensive characterization of mercury-activated signal transduction pathway alterations in immune system cells. Additionally, it is expected that the relationship with Dr. Gilbert will develop into a long-term collaboration, bringing the expertise of an established and well-published researcher to assist the career development of a newer investigator.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 环境和饮食暴露于少量汞化合物发生在生物体的整个生命周期。 虽然大规模暴露对健康的负面影响已经得到了很好的研究，但直到最近，研究人员才开始研究较低的慢性暴露的影响。 这些暴露诱导免疫系统的扰动，导致诱导不适当活化的B淋巴细胞产生抗自身抗体。 这种自身抗体的产生可以发展为自身免疫综合征，最明显的是类似于狼疮（具有抗DNA自身抗体）和硬皮病（具有抗DNA和抗核仁抗体）的疾病。 虽然已经进行了大量的工作，汞处理的细胞的功能改变，很少被检查在淋巴细胞中的信号转导途径。 拟议的工作将描述经汞处理的B淋巴细胞培养系激活后信号转导途径利用率的变化。 这项工作在这一领域是新颖的，因为汞暴露研究的主要焦点集中在更高剂量的汞或淋巴细胞以外的细胞上。 此外，这项工作将用于在后续阶段将该项目扩展到原代B淋巴细胞和T淋巴细胞培养谱系。 预计这项研究项目将提供必要的初步数据，使类似的，但扩大研究，中央阿肯色州大学。 第二个目标是微调这个项目，包括和培训本科生/毕业生。 因此，这个项目对我在UCA的研究计划的长期发展至关重要。 这个夏季项目将导致确定更多的建议，以寻求长期的联邦一级的支持。 最终目标是对免疫系统细胞中汞激活的信号转导途径改变进行广泛而全面的表征。 此外，预计与吉尔伯特博士的关系将发展为长期合作，将一位成熟且发表过大量文章的研究人员的专业知识用于协助新研究人员的职业发展。