权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Gene regulation in metastasis and new methods to analyze its microarray profiles

转移中的基因调控及其微阵列谱分析的新方法

基本信息

批准号：
8324663
负责人：
Zhengdong Zhang
金额：
$ 23.89万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2014-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8324663
关键词：
Algorithms Antibodies Binding Sites Biochemistry Biology Biophysics Breast Carcinoma Cancerous Cell Line Cessation of life Computational Biology Copy Number Polymorphism DNA DNA Binding DNA Sequence Rearrangement DNA copy number Data Distant Education Engineering Epithelial Event Gene Expression Gene Expression Regulation Gene Targeting Genes Genomics Goals Grant Health Human Institution K-Series Research Career Programs Malignant Epithelial Cell Malignant Neoplasms Mentors Mesenchymal Methods Microarray Analysis Molecular Molecular Profiling Mus Neoplasm Metastasis Organ Positioning Attribute Postdoctoral Fellow Primary Neoplasm Process Public Health Research Research Personnel Research Project Grants Research Proposals Research Training Snails Training Transcriptional Regulation United States United States National Library of Medicine Universities base blastomere structure career chromatin immunoprecipitation comparative genomic hybridization computer science computer studies epithelial to mesenchymal transition experience functional genomics interest neoplastic cell research study tumor

项目摘要

I am a National Library of Medicine research postdoctoral fellow in the Department of Molecular Biophysics and Biochemistry at Yale University. With this training/research proposal, I am applying to the Career Development Award. I had degreed education in both Biology and Computer Science and started my training and research in Computational Biology, the field of my research interest, in 1998. My immediate career goal is to have an extensive training in functional genomics, both computational and experimental. My long-term career goal is to become an independent investigator at a research institution and to make a substantial contribution to health-related research field. To achieve these goals, I will first conduct mentored research in functional genomics for two years under the guidance of Profs Gerstein and Snyder at Yale University and then apply for a research position at another institution. The goal of my proposed research is to obtain and analyze the profiles of gene expression, transcription regulation, and DNA copy number variation related to tumor metastasis progression as the five-year research plan. This proposal builds on my experience in genomic analysis of microarray data as a part of the ENCODE Project. For a training grant, the proposed research projects include both experimental and computational components. Specifically, I propose to identify the DNA-binding sites of two key regulators of tumor metastasis (Twist and Snail) in both normal murine embryonic cells and four murine isogenic mammary carcinoma cell lines (67NR, 168FARN, 4T07, and 4T1). In parallel, I will develop new algorithms for analyzing perturbed gene expression profiles to build a regulatory sub-network specific to the EMT process and identify other EMT regulators for further ChlP-chip experiments. As the target genes of the identified EMT regulators could be duplicated or deleted as a result of chromosomal micro-rearrangements during tumor metastasis, I will also carry out computational studies to analyze array-based comparative genomic hybridization data to identify such DNA copy number variations. I feel the proposed research is quite relevant to public health, becaus cancer is responsible for about 25% of all deaths in the United States. 90% of human cancer deaths, however, can be attributed to metastases, during which tumor cells spread from the primary tumor mass to distant organs. Clearly it is very important to understand what makes metastasis possible for a cancerous tumor and unravel its molecular mechanism.

我是国家医学图书馆分子生物物理学系的博士后研究员和耶鲁大学的生物化学有了这个培训/研究计划，我申请了职业发展奖。我有生物学和计算机科学的学位教育， 1998年，我在我的研究兴趣领域--计算生物学方面进行了培训和研究。我的直系职业目标是在功能基因组学方面进行广泛的培训，包括计算和实验。我的长期职业目标是成为研究机构的独立调查员，对健康相关研究领域做出重大贡献。为了实现这些目标，我将首先进行辅导在耶鲁大学Gerstein和Snyder教授的指导下，大学，然后申请在另一个机构的研究职位。本研究的目的是获得和分析基因表达谱、转录谱、转录谱和转录谱，调节，以及与肿瘤转移进展相关的DNA拷贝数变化，作为五年的随访。研究计划。这个建议建立在我的经验，在基因组分析的微阵列数据的一部分， ENCODE项目。在培训补助金方面，拟议的研究项目包括实验性和计算组件。具体来说，我建议确定两个关键监管机构的DNA结合位点，肿瘤转移（Twist和Snail）在正常小鼠胚胎细胞和四种小鼠同基因乳腺癌细胞系（67 NR、168 FARN、4 T07和4 T1）。与此同时，我将开发新的算法用于分析受干扰的基因表达谱，以构建对EMT特异的调控子网络处理和鉴定其他EMT调节剂用于进一步的ChIP芯片实验。作为靶基因，鉴定的EMT调节子可能由于染色体微重排而被复制或缺失在肿瘤转移过程中，我还将进行计算研究，分析基于阵列的比较，基因组杂交数据以鉴定此类DNA拷贝数变异。我觉得这项研究与公共健康非常相关，因为癌症占了大约25%，美国所有死亡人数的一半。然而，90%的人类癌症死亡可归因于转移，在此期间肿瘤细胞从原发肿瘤块扩散到远处器官。很明显，了解是什么使癌性肿瘤转移成为可能，并揭示其分子机制。