PAPILLOMAVIRUS E5 PROTEINS

乳头瘤病毒 E5 蛋白

• 批准号: 2084180
• 负责人: MELISSA CONRAD STOPPLER
• 金额: $ 8.8万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2084180
• 关键词: 3T3 cells; biological signal transduction; cell line; chimeric proteins; epithelium; epitope mapping; gel electrophoresis; gene expression; gene mutation; genetic transcription; growth factor receptors; host organism interaction; human papillomavirus; immunoelectron microscopy; immunofluorescence technique; intracellular transport; membrane proteins; molecular cloning; monoclonal antibody; neoplastic growth; nucleic acid hybridization; nucleic acid sequence; oligonucleotides; oncoproteins; phenotype; polymerase chain reaction; protein biosynthesis; protein sequence; protein structure function; reproductive system neoplasm; sexually transmitted diseases; tissue /cell culture; transfection /expression vector; viral carcinogenesis; virus cytopathogenic effect; virus infection mechanism; virus protein; western blottings

The intent of this proposal is to educate and train a medical graduate for a career in research. We have therefore designed a formal academic program and research project for Dr. Melissa Conrad which will provide her with the background and hands-on experience for developing into an independent research scientist. Her academic course work has been selected with the advice of 5 established professors in each of the departments in which she will train, and her research project will be performed in an established research laboratory under the direct supervision of Dr. Richard Schlegel. The proposed research project was chosen to integrate well into the main interests of Dr. Schlegel's laboratory to insure that Dr. Conrad would receive optimal training and interaction with the other postdoctoral researchers in the laboratory. finally, the research project chosen represents a state-of-the-art approach to studying a viral oncogene and its biological and biochemical activities. This project will therefore provide Dr. Conrad with training in the most current molecular, biochemical, and cellular techniques. The proposed research project will encompass both Phase 1 and Phase 2 of Dr. Conrad's training and consists of expressing and characterizing the E5 proteins of the human papillomaviruses. These viruses are sexually transmitted, infect the human genital tract, and initiate pathological lesions at these sites as well as contribute to the development of neoplasia, both benign and malignant. The HPV E5 proteins, whose counterpart in BPV-1 is a well-defined oncoprotein, are poorly characterized for function and biochemical activity. Interestingly, the HPV E5 proteins sort into two homologous groups: (1) those encoded by HPV- 6 and HPV-11 (which are associated with non-dysplastic epithelial lesions and benign genital tumors), and (2) those encoded by HPV-16 and HPV-18 (which are associated with dysplastic epithelial lesions and malignant genital tumors). The intent of the research proposal is to express the above HPV E5 proteins in a well-established vector which has been used successfully for the BPV-1 E5 protein. The HPV E5's will then be characterized biologically to determine whether they exhibit transforming and/or mitogenic activities. The HPV E5's will also be examined biochemically and compared with the E5 of BPV-1. After having established the biological and biochemical properties of the HPV E5's, Dr. Conrad will enter Phase 2 of her research training and undertake an extensive mutagenic analysis of the HPV E5's in order to define their functional domains. These studies will be important for understanding the different biological sequelae consequent to infection by the various types of HPV.

该建议的目的是教育和培训医学毕业生 研究职业。 因此，我们设计了一个正式的学术课程 和梅利莎·康拉德（Melissa Conrad）博士的研究项目，这将为她提供 背景和动手经验，用于发展为独立的 研究科学家。 她的学术课程工作已与 在她的每个部门中的5位知名教授的建议 将训练，她的研究项目将在一个既定的 理查德·施莱格尔（Richard Schlegel）博士直接监督的研究实验室。 拟议的研究项目被选为很好地整合到主要 Schlegel博士实验室的兴趣确保Conrad博士会 接受最佳培训和与其他博士后的互动 实验室的研究人员。 最后，选择的研究项目 代表了研究病毒癌基因及其的最先进方法 生物学和生化活动。 因此，该项目将提供 康拉德博士接受了最新分子，生化和 细胞技术。 拟议的研究项目将涵盖1阶段和第2阶段的2 康拉德博士的培训，包括表达和表征E5 人乳头瘤病毒的蛋白质。 这些病毒是性的 传播，感染人类生殖道并启动病理 这些部位的病变以及有助于发展 肿瘤，良性和恶性。 HPV E5蛋白，其 BPV-1中的对应物是一种明确的癌蛋白，很差 具有功能和生化活性的特征。 有趣的是， HPV E5蛋白分为两个同源组：（1）由HPV-编码的蛋白 6和HPV-11（与非塑性上皮病变有关 （2）由HPV-16和HPV-18编码的生殖器肿瘤）和（2） （与发育不良上皮病变和恶性有关 生殖器肿瘤）。 研究建议的目的是表达 在已建立的载体中，HPV E5蛋白上方已被使用 BPV-1 E5蛋白成功。 HPV E5的将是 在生物学上表征以确定它们是否表现出转化 和/或有丝分裂活动。 HPV E5也将进行检查 从生化，与BPV-1的E5进行了比较。 建立后 HPV E5的生物学和生化特性，Conrad博士将 输入她的研究培训的第2阶段并进行广泛的诱变 对HPV E5的分析是为了定义其功能域。 这些研究对于理解不同的生物学很重要 后遗症导致各种类型的HPV感染。