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Biological Response Indicators of Environment Stress Centers

环境应激中心的生物反应指标

基本信息

批准号：
8324839
负责人：
Stephen Morris Rappaport
金额：
$ 15万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
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/8324839
关键词：
Algorithms Area Aromatic Polycyclic Hydrocarbons Attention Bioinformatics Biological Biological Assay Biological Markers Biology Biosensing Techniques Biosensor Blood Blood Proteins Blood specimen Carcinogens Cell Line Cells Chemical Exposure Chemistry Collaborations Detection Development Disease Dose Drops Engineering Environment Environmental Exposure Enzyme-Linked Immunosorbent Assay Epidemiologist Epidemiology Etiology Exposure to Fingers Frequencies Gene Mutation Genes Goals Hematopoietic Neoplasms Hot Spot Human Immunoassay Individual Laboratories Libraries Link Lymphoma Malignant Neoplasms Mass Spectrum Analysis Measurement Measures Microfluidics Molecular Molecular Cytogenetics Molecular Epidemiology Molecular Profiling Mutation Mutation Spectra Normal Cell Pathway interactions Process Proteins Proteome Research Research Personnel Science Scientist Serum Serum Albumin Spottings Statistical Methods Stress System Technology Tissues Toxicogenomics Toxicology United States National Institutes of Health Work adduct asphalt base cancer risk case control epidemiology study experience genetic analysis innovation interest leukemia leukemia/lymphoma micro-total analysis system microsystems professor programs protein profiling repository response skills

项目摘要

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生物反应指标的总体主题是“血癌风险研究的生物标记物和生物传感器”。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，这些医生和流行病学家为这些疾病的分子流行病学研究维护储存组织储存库。它还突出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标记。项目1的主要目标是证明“蛋白质吸收学”作为一种真正的“组学”方法的可行性，这一方法对GEI具有普遍重要性，对暴露生物学尤其重要。我们建议丰富未知的人血清白蛋白半胱氨基加合物，然后在淋巴瘤患者和对照的血清中分析这些加合物。如果成功，这个项目将确定人类未知的发起人淋巴瘤。项目2-高通量检测作为血液病癌症风险生物标志物的基因突变。该项目将开发和应用芯片实验室技术，以研究与人类白血病机制有关的单个细胞的突变谱。通过从单个细胞中扩增DNA，我们将测量被正常细胞包围的易感个体细胞关键位点的突变谱。然后，通过发展高通量单细胞PCR方法来检测Low 为了研究白血病中重要突变的频率，我们将为与白血病相关的关键基因或区域的突变建立一个有偏见的热点文库。项目3-分子和细胞生物标记物的先进生物传感。该项目将开发生物传感器，使在实验室或现场使用一滴血液快速、方便地进行免疫分析成为可能。它将通过测量血液中多环芳烃的蛋白质加合物来验证生物传感器沥青和建筑工人的血迹。通过实现这些目标，我们的中心将开辟有关化学暴露与人类癌症之间联系的重要新途径。它还将开发技术，在大规模流行病学研究中将蛋白质加合物用作内剂量的生物标记物。