Temporal and spatial profiling of gene expression during polar growth of Aspergil

曲霉极地生长过程中基因表达的时空分析

基本信息

批准号：
7635743
负责人：
MICHELLE MOMANY
金额：
$ 14.75万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-11 至 2011-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Invasive aspergillosis (IA) is the most frequent infectious cause of death in leukemia and bone marrow transplant patients. The conidia of Aspergillus fumigatus, the filamentous fungus that is the most common cause of IA, are inhaled and germinate in the lung. Like all filamentous fungi A. fumigatus undergoes highly polar growth via germ tubes and later branches. This highly polar tip growth allows A. fumigatus to invade blood vessels and tissues resulting in the necrosis characteristic of IA. Despite the importance of polar growth to IA, little is known about the molecular mechanisms of polar growth in A. fumigatus. The proposed research will use microarray profiling to identify genes that are differentially transcribed and/or asymmetrically localized during polar growth in A. fumigatus. Temporal profiles of genes expressed during polar growth will be generated using RNA isolated from synchronous cultures just before and after germ tube and branch emergence and during elongation of hyphae and branches. Spatial profiles of genes expressed during polar growth will be generated using RNA isolated from specific regions of germ tubes, hyphae and branches with laser microcapture techniques. RNA will be labeled and hybridized to existing PFGRC A. fumigatus microarrays and expression patterns will be analyzed. Identification of genes that are differentially transcribed and/or asymmetrically localized during polar growth will lay the foundation for a comprehensive research program focusing on polar growth in A. fumigatus and its role in IA. PUBLIC HEALTH RELEVANCE: Invasive aspergillosis (IA), an often fatal disease of the immunocompromised, is caused when the spores of Aspergillus fumigatus are inhaled and grow in the lung. Like other filamentous fungi, A. fumigatus sends out long tubular cells known as hyphae into the environment searching for nutrients and in IA it is these hyphae which cause the destruction of host tissue. The proposed research will identify genes that allow A. fumigatus to make hyphae and so will uncover new ways of combating IA.

描述（由申请人提供）：浸润性曲霉病（IA）是白血病和骨髓移植患者中最常见的传染性死亡原因。烟曲霉的分生孢子是最常见的IA原因的丝状真菌，在肺中被吸入并发芽。像所有丝状真菌一样，富马图斯通过细菌管和后来的分支也经历了高极性生长。这种高极尖端的生长使烟曲霉能够侵入血管和组织，从而导致IA的坏死特征。尽管极性生长对IA的重要性，但对烟曲霉的极性生长的分子机制知之甚少。拟议的研究将使用微阵列分析来识别在富马图曲霉的极性生长过程中差异转录和/或不对称局部的基因。在细菌管和分支出现之前和之后以及菌丝和分支的伸长期间，使用从同步培养物中分离出的RNA，将产生在极性生长过程中表达的基因的时间谱。在极性生长过程中表达的基因的空间谱将使用从细菌管，菌丝和分支的带有激光微功能技术的特定区域分离的RNA产生。 RNA将被标记并杂交与现有的PFGRC A. Fumigatus微阵列和表达模式。鉴定在极性生长期间差异转录和/或不对称定位的基因将为综合研究计划奠定基础，该计划重点是富马图斯的极性生长及其在IA中的作用。公共卫生相关性：侵入性曲霉菌病（IA），通常是一种致命的免疫功能低下的致命疾病，是当吸入曲霉菌的孢子并在肺中生长时引起的。像其他丝状真菌一样，烟曲霉将被称为菌丝的长管状细胞发送到寻找营养的环境中，而在IA中，这些菌丝会造成宿主组织的破坏。拟议的研究将确定允许烟曲霉制作菌丝的基因，因此可以发现打击IA的新方法。