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: 10371532
• 负责人: Erik Christian Andersen
• 金额: $ 24.26万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371532
• 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; DNA; DNA Sequence; Data; Databases; Development; Disease; Dose; Engineering; Evaluation; Evolution; Foundations; Generations; Genes; Genetic; Genetic Crossing Over; Genetic study; Genome; Genomics; Genotype; Health; Hi-C; High School Student; Human; Inbreeding; Insecta; Label; Laboratories; Life; Location; Maintenance; Manuals; Maps; Mediating; Meiosis; 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 Grants; 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-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.

C的遗传和基因组工具。Briggsae研究：项目概要 利用微小线虫秀丽隐杆线虫的研究已经产生了许多基础性的 发现细胞死亡的遗传基础，有机体衰老，microRNA的生物学作用，以及 其他与人类健康相关的基本主题。是对C. elegans是那些在相关的线虫Caushabditis briggsae，其中分享了许多实验， C.的优势但它在大约3000万年前与之分道扬镳。C. Briggsae提供了一个 比较遗传学研究的平台，导致保守过程的有效分析，以及 发现基因、通路和网络的进化。这些比较研究对于 建立研究严谨性和验证发现。此外，C. elegans和C. Briggsae在生活史特征和种群全球分布方面的研究意味着， 种群生物学问题、多基因性状或宿主-病原体、寄生和机会关系 与病毒、细菌和昆虫的接触最好用C.布里格斯比C.优美的尽管有这些 重要的特征，许多遗传资源是必不可少的标准C。elegans研究不是 可用于使用C.布里格塞随着基因编辑和基因工程技术的应用效率不断提高， CRISPR介导的方法，重要的基因组和遗传工具的可用性是这些方法的关键限制。 重要的比较研究。 该项目将产生这些研究资源，以解决这一差距。作为第一个目标，两个端粒- 端粒C.将使用一组经验证的基因模型来产生具有经验证的基因模型的布里格斯参考基因组 互补的长和短序列读取方法和验证技术。这些数据将 整合到NCBI和Wormbase中，Wormbase是使用C.线虫和 相关的线虫。第二个目标将产生并验证一组基因平衡器， 阻止减数分裂交换的染色体。这些遗传工具对于维持和 评估纯合致死或不育突变，目前通过以下方式维持 费力的过程。基因平衡器还将允许进行目前尚未进行的更复杂的基因实验。 在C.布里格塞最后，具有用于将DNA引入定义的宿主细胞的“安全港”着陆位点的菌株， 在C的位置。briggsae基因组将被制作和验证。这些菌株将允许控制， 将单拷贝插入克隆可重复地引入C. Briggsae，并允许一系列实验 操作，包括两个物种之间的基因“节点交换”，以及对开发用于 C. elegans直接在C.布里格塞这些目标将共同产生消除重要障碍的关键工具 进行基因分析。