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）：这项研究将主要在阿根廷圣马丁进行，在Fundicion Instituto de Investiones Biotecnologicas，Nacional de General San Martin大学与Juan J. Cazzulo博士合作，作为NIH Grant 1R01 AI068647。 Chagas疾病的化学疗法仅限于毒性相对较高且功效有限的药物。我们的研究重点是通过研究寄生虫所需的代谢系统，但在人类宿主中没有等效的代谢系统，以合理地寻求对Cruzi的有效化学治疗方法。寄生虫对营养和过度渗透胁迫的反应是其在载体和哺乳动物宿主中的生存至关重要的，其研究可能导致发现新靶标。压力条件通常会在细胞水平上产生多种生理反应。压力条件通常会在细胞水平上产生多种生理反应。当提交t. cruzi的表载剂以使细胞减少体积而没有恢复，并受到上调或下调许多基因的表达。在几个转录本的3'-UTR中发现了候选结构RNA基序，并在比较完整的转录组时富含实验数据集。这些顺式元素可能与响应高渗应激的全局表达模式的转录后机制有关。该提案将集中在以下特定目的上：具体目的1：研究提交过度渗透应激的克鲁齐基因表达的变化；具体目的2：研究在克鲁齐（T. 公共卫生相关性：在美洲，从北部的墨西哥到南部的阿根廷和智利，有16至1900万人感染了Cruzi锥虫菌（Cruzi），这是Chagas疾病的原因。估计每年发病率为561,000例。查加斯病是一种媒介传播的疾病，也可以通过输血传播，是拉丁美洲充血性心力衰竭的主要原因。我们的目标是找到干扰克鲁齐代谢途径的方法，以此作为控制由这种和类似寄生虫引起的感染的策略。克鲁氏杆菌对营养和过度渗透应激的反应与哺乳动物细胞对相似胁迫的反应不同，其研究可能导致发现锥虫剂剂的新靶标。这项工作旨在研究这些途径在T. Cruzi中的作用和意义。