Identifying Regulation of Cell Cycle Gene Networks in E*

识别 E* 中细胞周期基因网络的调控

基本信息

批准号：
7337124
负责人：
UPINDER SINGH
金额：
$ 3.09万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-02-01 至 2010-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7337124
关键词：
Amebiasis Amebic colitis Biology Bispecific Antibody 2B1 Cell Cycle Cell Cycle Progression Cell Cycle Regulation Cell Nucleus Cell Proliferation Cell division Cell surface Colitis Collaborations Colon Colonic Diseases Condition Cyclins DNA Microarray Chip DNA Microarray format Data Disease Dominant-Negative Mutation Double-Stranded RNA Drug resistance Entamoeba dispar Entamoeba histolytica Enterobacteriaceae Enterocytes Environment Erythrocytes Erythrophagocytosis Eukaryota Eukaryotic Cell Facility Construction Funding Category Family Gene Expression Generations Genes Genetic Genome Genomics Genus Cola Goals Grant Hand Homologous Gene Human In Vitro India Infection Ingestion Institutes Invasive Laboratories Lead Ligand Binding Liver Abscess Medical Surveillance Methodology Methods Microarray Analysis Molecular Numbers Nutrient Parasites Parents Pathogenesis Pathway interactions Pattern Phagocytosis Phase Phenotype Quality Control Regulation Reproducibility Research Sequence Homology Signal Transduction Stimulus Stress Technology Transfer Testing Transcriptional Regulation United States National Institutes of Health Virulence Virulence Factors Work Writing base cdc Genes cohort deprivation genetic analysis in vivo insight interest member monolayer mouse model novel parent grant pathogen prevent research study response species difference tool

项目摘要

This research will be done primarily at the Bose Institute in Calcutta, India in collaboration with Anuradha Lohia as an extension of NIH grant R01AI 53724. The human pathogen Entamoeba histolytica is responsible for causing amoebic dysentery and liver abscesses. Infection of the human gut is quickly followed by proliferation and multiplication of the parasite, which may then lead to colonic disease. We are interested in identifying molecular factors regulating cell proliferation in this protist parasite, in an effort to devise new strategies to prevent amoebiasis. The goal of the parent proposal is to identify novel amoebic virulence factors by microarray based transcriptional profiling. The FIRCA supplement is written with Prof. Anuradha Lohia who has been studying the regulation of cell cycle progression Entamoeba histolytica. Results from Anuradha's laboratory in India have shown that in E. histolytica genome reduplication may occur without cell division and single nuclei may contain several genome contents during the proliferative phase (Gangopadhyay et al, 1997a; Das and Lohia, 2002). Therefore, unlike most eukaryotes the cell cycle of E. histolytica does not appear to be controlled by known checkpoint surveillance mechanisms. It would be important therefore to identify a global profile of genes that regulate cell cycle progression in E. histolytica. In this proposal we plan to use dsRNA interference (Kaur and Lohia, 2004) to down-regulate cell cycle homologues- Eh Cdks and cyclins, followed by transcriptional profiling using microarrays in order to identify groups of genes controlled by CDKs and cyclins in E. histolytica. This work has important implications for identifying novel aspects of cell cycle control in E. histolytica. .Additionally, this project is an ideal collaborative environment in which a main goal is technology transfer (use and anlaysis of microarray data) to the Lohia lab in India. Arrays as a post-genomic tools are powerful yet highly specialized, thus the "hands-on" use of this application by Lohia's group is an important component of this work.

这项研究将主要在印度加尔各答的Bose Institute与Anuradha合作进行 Lohia作为NIH赠款R01AI 53724的扩展。人类病原体Entamoeba Histolictica负责引起阿米巴痢疾和肝脏脓肿。人类肠道的感染很快被寄生虫增殖和繁殖然后可能导致结肠疾病。我们有兴趣识别调节细胞的分子因子这种原生寄生虫的扩散是为了制定新的策略来预防半径。目标父母的建议是通过基于微阵列的转录来识别新型的反对性毒力因子分析。 FIRCA补充剂是由一直在研究法规的Anuradha Lohia教授编写的细胞周期进程entamoeba Histoltica。印度阿努拉达（Anuradha 在没有细胞分裂的情况下发生，单核可能在增殖过程中包含几个基因组含量阶段（Gangopadhyay等，1997a; Das和Lohia，2002）。因此，与大多数真核生物不同 E. istolytica的大肠杆菌似乎不受已知的检查点监视机制的控制。这将是因此，重要的是要确定调节组织溶液性细胞周期进程的基因的全局谱。在此提案中，我们计划使用DSRNA干扰（Kaur and Lohia，2004）下调细胞周期同源物 - EH CDK和细胞周期蛋白，然后使用微阵列进行转录分析，以识别由CDK和细胞周期蛋白控制的基因组中溶作息肉。这项工作对识别E. histoltica中细胞周期控制的新方面。在此方面，这个项目是理想的主要目标是技术转移（微阵列数据的使用和Anlaysis）的协作环境到印度的Lohia实验室。作为后基因组工具的阵列具有强大但高度专业化，因此 Lohia小组对此应用程序的“动手”使用是这项工作的重要组成部分。