COMPARATIVE GENOMICS OF PARASITIC NEMATODES

描述(申请人提供)：寄生线虫感染世界上一半以上的人口，导致严重的发病率和死亡率。线虫基因组的特征提供了关于这些寄生虫的基本分子信息，加速了新的诊断和治疗方法的基础研究和开发。华盛顿大学基因组中心已经从30个寄生虫物种中产生并公布了40多万个cDNA，对4个基因组进行了测序，以起草覆盖范围，包括主要人类寄生虫群体的代表在内的另外10个基因组正在进行中。这项建议的三个目标是分析扩展的线虫序列，以大大提高对寄生线虫生物学和细胞途径的理解。首先，我们将开发和使用生物信息学工具来处理、组装和注释来自所有测序平台的传入数据。这些基因组资源还将通过中央寄生线虫数据库Nematode.net传播给更广泛的研究社区。其次，分析将重点放在保守的和/或分类受限的生化途径上，包括可能被证明是有用的药物靶标的蛋白质。第三，我们将研究环境信息处理和内分泌系统中涉及的蛋白质中线虫特异性插入和缺失的性质和意义。预期的结果将促进和促进发现和发展新的干预措施，以控制这些重要的寄生虫，并降低其相关发病率和死亡率。 公共卫生相关性：继续开发用于研究寄生线虫的分子信息、生物信息学工具和试剂是至关重要的，因为它们感染了世界上一半以上的人口，是人类发病率的主要原因。该项目的主要目标是实施比较基因组学方法来研究这些重要寄生虫的生物学和细胞途径，从长远来看，这将有助于改进诊断、疫苗和驱虫药，以广泛控制寄生虫。

DESCRIPTION (provided by applicant): Parasitic nematodes infect over half the world's population, resulting in significant morbidity and mortality. Characterization of nematode genomes provides fundamental molecular information about these parasites accelerating basic research and development of new diagnostics and therapeutics. Washington University's Genome Center has generated and made public over 400,000 cDNAs from 30 parasitic species, sequenced 4 genomes to draft coverage with ten more underway including representatives of the major human parasitic groups. The three aims in this proposal analyze the expanding nematode sequences to substantially improve understanding of parasitic nematode biology and cellular pathways. First, we will develop and use bioinformatic tools to process, assemble, and annotate incoming data from all sequencing platforms. These genomic resources will also be disseminated to the wider research community through the centralized parasitic nematode database, Nematode.net. Second, analysis will focus on biochemical pathways conserved and/or taxonomically restricted including proteins that may prove useful as drug targets. Third, we will study the nature and implications of nematode-specific insertions and deletions in proteins involved in environmental information processing and endocrine system. The expected outcome will facilitate and promote the discovery and development of novel interventions to control these important parasites and reduced their associated morbidity and mortality. PUBLIC HEALTH RELEVANCE: The continued development of molecular information, bioinformatics tools, and reagents for the study of parasitic nematodes is crucial, as they infect over half of the world's population and are a leading cause of human morbidity. The main goal of this project is to implement comparative genomics approaches to study the biology and cellular pathways of these important parasites, which on a long run will contribute to improved diagnostics, vaccines, and anthelmintic drugs for broad parasite control.