Global gene expression analysis of Trypanosoma cruzi under hyperosmotic stress

高渗胁迫下克氏锥虫全局基因表达分析

• 批准号: 8010207
• 负责人: ROBERTO DOCAMPO
• 金额: $ 5.53万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8010207
• 关键词: Accounting; Affect; Americas; Amino Acids; Argentina; Biology; Blood Transfusion; Cells; Cellular Stress; Chagas Disease; Chile; Collaborations; Complex; Congestive Heart Failure; Cyclic AMP; Data Set; Drug effect disorder; Elements; Gene Expression; Gene Expression Profile; Genes; Goals; Grant; Human; Incidence; Infection Control; Latin America; Lead; Life Cycle Stages; Mammalian Cell; Mediating; Metabolic; Metabolic Pathway; Mexico; Microtubules; Molecular; Names; Nutritional; Organelles; Osmoregulation; Parasites; Pathway interactions; Pattern; Pharmaceutical Preparations; Physiological; RNA; Recovery; Research; Role; Signal Pathway; Stress; Swelling; System; Toxic effect; Transcript; Trypanocidal Agents; Trypanosoma; Trypanosoma cruzi; United States National Institutes of Health; Untranslated Regions; Vacuole; Vector-transmitted infectious disease; Water Movements; Work; chemotherapy; design; novel; parent grant; public health relevance; response; vector; water channel

DESCRIPTION (provided by applicant): This research will be done primarily in San Martin, Argentina, at Fundacion Instituto de Investigaciones Biotecnologicas, Universidad Nacional de General San Martin, in collaboration with Dr. Juan J. Cazzulo, as an extension of NIH Grant 1R01 AI068647. Chemotherapy of Chagas disease is restricted to drugs with relatively high toxicity and limited efficacy. Our research focuses on the rational search for effective chemotherapeutic treatments for T. cruzi by investigating metabolic systems necessary for parasites but without equivalent counterparts in the human host. The response of the parasite to nutritional and hyperosmotic stresses is fundamental for its survival within the vector and mammalian hosts and its study could lead to the finding of novel targets. Stress conditions usually lead to a variety of physiological responses at the cellular level. Stress conditions usually lead to a variety of physiological responses at the cellular level. When epimastigotes of T. cruzi were submitted to hyperosmotic stress the cells reduced their volume without recovery, and up-regulated or down- regulated the expression of a number of genes. Candidate structural RNA motifs were found in the 3'-UTR of several transcripts and enriched in the experimental dataset when comparing over the complete transcriptome. These cis-elements could be involved in post-transcriptional mechanisms underlying a global expression pattern in response to hyperosmotic stress. This proposal will be focused in the following specific aims: Specific aim 1: to study the changes in gene expression in T. cruzi submitted to hyperosmotic stress; Specific aim 2: to investigate the role of the cis-elements identified in the 3'-UTR of genes affected by hyperosmotic stress in gene expression of T. cruzi. PUBLIC HEALTH RELEVANCE: In the Americas, from Mexico in the North to Argentina and Chile in the South, there are 16 to 19 million people infected with Trypanosoma cruzi, the causative agent of Chagas disease. Estimated yearly incidence amounts to 561,000 cases. Chagas disease is a vector-borne disease that can also be transmitted by blood transfusion and is the leading cause of congestive heart failure in Latin America. Our goal is to find ways of interfering with Trypanosoma cruzi metabolic pathways as a strategy of controlling infections caused by this and similar parasites. The response of T. cruzi to nutritional and hyperosmotic stresses is different from the response of mammalian cells to similar stresses and their study may lead to the discovery of new targets for trypanocidal agents. This work is designed to investigate the roles and significance of these pathways in T. cruzi.

描述（由申请人提供）：本研究将主要在阿根廷圣马丁进行，在圣马丁国立大学生物技术研究基金会，与Juan J. Cazzulo博士合作，作为NIH资助1R01 AI068647的延伸。恰加斯病的化疗仅限于毒性相对较高且疗效有限的药物。我们的研究重点是通过研究寄生虫所必需的代谢系统，而在人类宿主中没有相应的代谢系统，来合理地寻找有效的克氏锥虫化疗方法。寄生虫对营养和高渗胁迫的反应是其在媒介和哺乳动物宿主内生存的基础，对其的研究可能导致发现新的靶点。应激条件通常会导致细胞水平上的各种生理反应。应激条件通常会导致细胞水平上的各种生理反应。在高渗胁迫下，克氏T.的附毛体细胞体积减少而不恢复，并上调或下调一些基因的表达。在几个转录本的3'-UTR中发现了候选结构RNA基序，并且在与完整转录组进行比较时在实验数据集中得到了丰富。这些顺式元件可能参与了高渗胁迫下全球表达模式的转录后机制。本课题将集中在以下几个方面：具体目的1：研究高渗胁迫下克氏体基因表达的变化；具体目的2：探讨高渗胁迫影响基因3′-UTR中鉴定的顺式元件在克氏体基因表达中的作用。