Genetic and genomic tools for C. briggsae research

用于 C. briggsae 研究的遗传和基因组工具

• 批准号: 10582658
• 负责人: Erik Christian Andersen
• 金额: $ 18.84万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10582658
• 关键词: Address; Aging; Alleles; Apoptosis; Bacteria; Biological; Biological Process; C. elegans genome; CRISPR/Cas technology; Caenorhabditis; Caenorhabditis elegans; Cell Death; Chromosome inversion; Chromosomes; Clustered Regularly Interspaced Short Palindromic Repeats; Collection; Communities; Comparative Study; Complement; Complex; Conserved Sequence; DNA; DNA Sequence; Data; Databases; Development; Disease; Dose; Engineering; Evaluation; Evolution; Experimental Genetics; Generations; Genes; Genetic; Genetic Crossing Over; Genetic study; Genome; Genomics; Genotype; Health; Heterozygote; Hi-C; High School Student; Human; Inbreeding; Insecta; Label; Laboratories; Life; Location; Maintenance; Manuals; Maps; Mediating; Messenger RNA; Methods; MicroRNAs; Microscopic; Modeling; Mutation; Nematoda; Organism; Pathway interactions; Phenotype; Polygenic Traits; Population Biology; Population Distributions; Process; RNA Interference; RNA Probes; Reagent; Recombinants; Reproducibility; Research; Research Personnel; Research Project Summaries; Resource Development; Resources; Role; Site; Sterility; Techniques; Technology; Testing; Transgenes; Transgenic Organisms; Update; Validation; Virus; WormBase; biological systems; comparative; comparative genomics; effectiveness validation; experience; experimental study; flexibility; gene function; genetic analysis; genetic resource; genome resource; genome-wide; genomic data; genomic locus; genomic tools; improved; in vivo; interest; life history; mutant; nanopore; pathogen; prevent; reagent testing; reference genome; repaired; response; telomere; tool; tool development; trait; undergraduate student

Genetic and Genomic tools for C. briggsae research: Project Summary Research using the microscopic nematode Caenorhabditis elegans has produced many foundational discoveries in the genetic basis of cell death, organismal aging, the biological roles for microRNAs, as well as other fundamental topics that are relevant to human health. An important complement to studies on C. elegans is those on the related nematode Caenorhabditis briggsae, which shares many of the experimental strengths of C. elegans, but from which it diverged approximately 30 million years ago. C. briggsae provides a platform for comparative genetic studies, leading to efficient analysis of conserved processes, as well as discoveries on the evolution of genes, pathways and networks. These comparative studies are important in establishing research rigor and validating findings. In addition, differences between C. elegans and C. briggsae in terms of life history traits and global distribution of populations means that many studies addressing population biology questions, polygenic traits, or host-pathogen, commensal, and opportunistic relationships with viruses, bacteria, and insects are better done with C. briggsae than with C. elegans. Despite these important features, many genetic resources that are essential for standard C. elegans research are not available for studies using C. briggsae. With the increasing efficiency of genetic editing and engineering using CRISPR-mediated methods, the availability of important genomic and genetic tools is a key limitation for these important comparative studies. This project will produce these research resources to address this gap. As a first aim, two telomere-to- telomere C. briggsae reference genomes with validated gene models will be produced, using sets of complementary long and short sequence read methods and validation techniques. These data will be incorporated into NCBI and Wormbase, the online database used by researchers who use C. elegans and related nematodes. A second aim will produce and validate a set of genetic balancers, or rearranged chromosomes that prevent meiotic crossing over. These genetic tools are critical for the maintenance and evaluation of mutations that are homozygous lethal or sterile and that are currently maintained through laborious processes. Genetic balancers will also permit more complex genetic experiments not currently feasible in C. briggsae. Finally, strains with "safe harbor" landing sites for the introduction of DNA into defined locations in the C. briggsae genome will be produced and validated. These strains will permit controlled, reproducible introduction of single copy insertion clones into C. briggsae, and permit a range of experimental manipulation including gene "node swaps" between the two species, and the testing of reagents developed for C. elegans directly in C. briggsae. Together, these aims will produce key tools that remove important barriers to genetic analysis in this research organism.

用于Briggsae C. c. briggsae研究的遗传和基因组工具：项目摘要 使用微观线虫秀丽隐杆线虫的研究产生了许多基础 以细胞死亡的遗传基础，生物衰老，microRNA的生物学作用以及 与人类健康有关的其他基本主题。对C的研究的重要补充。 秀丽隐杆线虫是相关线虫上的caenorhabditis briggsae，它具有许多实验性 秀丽隐杆线虫的优势，但大约在大约3000万年前就从中差异。 C. briggsae提供了 比较遗传研究的平台，导致对保守过程的有效分析以及 关于基因，途径和网络发展的发现。这些比较研究在 确立严格的研究和验证发现。另外，秀丽隐杆线虫和C. 关于人生历史特征和人口的全球分布，briggsae意味着许多研究 人口生物学问题，多基因性状或宿主病原，共同和机会主义关系 与病毒，细菌和昆虫相比，细菌和昆虫的效果更好。尽管如此 重要特征，许多对标准秀丽隐杆线虫研究至关重要的遗传资源不是 可用于使用C. briggsae的研究。随着基因编辑和工程效率的提高 CRISPR介导的方法，重要的基因组和遗传工具的可用性是这些的关键限制 重要的比较研究。 该项目将产生这些研究资源来解决这一差距。作为第一个目标，两个端粒到 将使用一组经过验证的基因模型的端粒C. briggsae参考基因组，使用一组 互补的长序列读取方法和验证技术。这些数据将是 纳入NCBI和WORMBase，这是使用C. elegans和C. equans和 相关线虫。第二个目标将产生并验证一组遗传平衡器或重新排列 防止减数分裂越过的染色体。这些遗传工具对于维护和 评估纯合致死或无菌的突变，目前通过 费力的过程。遗传平衡器还将允许目前不再进行更复杂的遗传实验 可行的Briggsae。最后，与“安全港”着陆点的菌株将DNA引入定义 将产生和验证Briggsae基因组中的位置。这些菌株将允许受控， 可重现单副本插入克隆到briggsae中，并允许一系列实验 操作包括两个物种之间的基因“节点掉期”，以及针对开发的试剂的测试 秀丽隐杆线虫直接在briggsae中。这些目标在一起将产生关键工具，以消除重要的障碍 在该研究生物中进行遗传分析。