CHARACTERIZATION OF LYMPHOCYTE SIGNAL TRANSDUCTION IN RESPONSE TO MERCURY EXPOSU

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级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的情况发生在生物体的整个生命周期中。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长期暴露的影响。这些暴露会导致免疫系统的紊乱，导致不适当激活的B淋巴细胞产生抗自身抗体。这种自身抗体的产生可发展为自身免疫综合征，最明显的疾病类似于狼疮(带有抗DNA自身抗体)和硬皮病(带有抗DNA和抗核仁抗体)。 虽然在汞处理细胞的功能改变方面已经做了很多工作，但很少有人研究与淋巴细胞中的信号转导途径有关的问题。这项拟议的工作将表征汞处理的B淋巴细胞培养株在激活时信号转导途径利用的变化。这项工作对这一领域来说是新的，因为汞暴露研究的主要焦点要么是更高剂量的汞，要么是淋巴细胞以外的细胞。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，将类似但扩大的研究带到中央阿肯色大学。第二个目标是对该项目进行微调，以纳入和培训本科生/毕业生。因此，这个项目对我在UCA的研究项目的长期发展至关重要。这个夏季项目将产生确定的额外提案，以寻求联邦政府的长期支持。最终目标是对免疫系统细胞中汞激活的信号转导途径的变化进行广泛和全面的表征。此外，预计与吉尔伯特博士的关系将发展为长期合作，带来一位久负盛名的研究人员的专业知识，以帮助一名新的调查人员的职业发展。

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.