Biological Response Indicators of Environment Stress Centers

环境应激中心的生物反应指标

• 批准号: 7851431
• 负责人: Stephen Morris Rappaport
• 金额: $ 114.7万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7851431
• 关键词: Biological; Response; Indicators; Environment; Stress

The overall theme of Berkeley's Biological Response Indicators of Environmental Stress Center is "Biomarkers and Biosensors for Studies of Blood Cancer Risks." This theme reflects the long-standing interests of our investigators in the etiology of human leukemias and lymphomas and our close associations with clinicians and epidemiologists who maintain repositories of stored tissues for molecular epidemiology studies of these diseases. It also highlights particular research strengths of our investigators in the areas of microsensing, chemistry, toxicology, bioinformatics, and exposure biology. Our Program has the following three projects and goals: Project 1 - Protein Adducts as Molecular Signatures of Carcinogen Dose. The major goal of Project 1 is to demonstrate the viability of 'protein adductomics' as a true 'omics' approach, one of general importance to the GEI and of particular importance to Exposure Biology. We propose to enrich unknown cysteinyl adducts of human serum albumin and then to profile these adducts in the serum of lymphoma cases and controls. If successful, this project will identify unknown initiators of human lymphomas. Project 2 - High Throughput Detection of Genetic Mutations as Biomarkers of Hematological Cancer Risk. This project will develop and apply lab-on-a-chip technologies to investigate mutation spectra in individual cells that are involved with the mechanism of human leukemia. By amplifying DMA from single cells, we will measure mutation spectra at critical loci in susceptible individual cells surrounded by normal cells. Then, by developing high-throughput single-cell PCR assays to detect low frequencies of mutations of importance in leukemia, we will prepare a biased library of hot-spots for mutations in key genes or regions related to leukemia. Project 3 - Advanced Biosensing for Molecular and Cellular Biomarkers. This project will develop biosensors that make it possible to perform immunoassays quickly and conveniently, either in a laboratory or in the field, using a single drop of blood. It will validate the biosensors by measuring blood protein adducts of polycyclic aromatic hydrocarbons in the blood from asphalt and construction workers. By achieving these goals our Center will open up important new avenues of inquiry regarding the links between chemical exposures and human cancers. It will also develop the technology to utilize protein adducts as biomarkers of internal dose in large epidemiology studies.

伯克利环境压力中心的生物反应指标的总体主题是“血液癌症风险研究的生物标志物和生物传感器”。“这一主题反映了我们的研究人员对人类白血病和淋巴瘤病因学的长期兴趣，以及我们与临床医生和流行病学家的密切联系，他们为这些疾病的分子流行病学研究保存了储存的组织。它还强调了我们的研究人员在微传感，化学，毒理学，生物信息学和暴露生物学领域的特殊研究优势。我们的计划有以下三个项目和目标：项目1 -蛋白质加合物作为致癌物剂量的分子特征。项目1的主要目标是证明“蛋白内收体”作为一种真正的“组学”方法的可行性，这对GEI具有普遍重要性，对暴露生物学具有特别重要性。我们建议丰富未知的半胱氨酰加合物的人血清白蛋白，然后这些加合物的淋巴瘤病例和对照血清中的配置文件。如果成功，该项目将确定未知的人类活动的发起者。 淋巴瘤项目2 -高通量检测遗传突变作为血液癌症风险的生物标志物。该项目将开发和应用芯片实验室技术来研究与人类白血病机制有关的单个细胞中的突变谱。通过扩增来自单细胞的DMA，我们将测量被正常细胞包围的易感个体细胞中关键位点的突变谱。然后，通过开发高通量单细胞PCR检测来检测低表达的 为了了解白血病中重要突变的频率，我们将准备一个与白血病相关的关键基因或区域突变的热点偏倚文库。项目3 -分子和细胞生物标志物的先进生物传感。该项目将开发生物传感器，使其能够在实验室或现场使用一滴血快速方便地进行免疫测定。它将通过测量血液中多环芳烃的血液蛋白加合物来验证生物传感器。 沥青和建筑工人的血通过实现这些目标，我们中心将开辟重要的新途径，研究化学品暴露与人类癌症之间的联系。它还将开发利用蛋白加合物作为大型流行病学研究中内照射剂量生物标志物的技术。