Research Resources for Model Amphibians

该应用程序建议开发基本的基因组和生物信息资源，以更好地使 紫杉醇(Ambystoma Micianum)Axolotl为识别机制提供了最佳模型 可以转化为人类的再生。这是因为它可以再生多个受损的身体部位， 包括整个四肢、脊髓和大脑，因为它与人类分享四足动物的生物学。理解 Axolotels如何再生复杂组织可能揭示激活人体组织内干细胞的机制 整理和改造受损的组织。除了再生，紫杉醇还出现了许多未开发的疾病 在此之前用传统开发方法确定并严格检查的模型 遗传学/基因组学时代。随着我们最近开发的第一个染色体规模的紫杉醇组装 基因组，这些和未来几年将通过基因组编辑创建的新模型可以被推进 第一次对生物医学研究产生重大影响。然而，为了推进这些模型，改进 需要基因组组装和新的数据集，以实现对大型Axolotl的全基因组研究 基因组。为了实现这些目标，我们提出了三个具体目标。在目标1中，我们将解决内部和 当前组装内的种内变异，并解决阻碍 32 GB基因组中~6 GB的放置。具体地说，我们将采用强大的三人组投篮策略， 利用Aaxolotl×Tiger Salamander(A.tigrum)杂交后代的DNA长阅读测序。这 方法利用在产生种间杂交方面的数十年经验来解决组装差距/错误 并将基因模型准确地放置在它们的非编码调控环境中。此外，我们还将分析 来自最适合实验室遗传采样的家系分支的10个AGSC无性系的序列数据 多样性。在目标2中，我们将进行Chip-Seq以确定组蛋白翻译后修饰在 尾巴和肢体再生。日本血吸虫胚胎、幼虫和成虫模型表观遗传标记的特征 再生将为再生研究提供新的资源，并推动社区在执行 全基因组研究。目标3将满足重要的社区需求，方便用户访问大规模 基因组数据集与研究人员基因组和生物信息学能力的提高 社区。这些目标的实现将大大促进紫杉醇作为生物医学动物模型的发展 研究。

This application proposes to develop fundamental genomic and bioinformatic resources that will better enable studies of the axolotl (Ambystoma mexicanum). The axolotl provides the best model for identifying mechanisms of regeneration that can translate to humans. This is because it can regenerate multiple damaged body parts, including whole limbs, spinal cord, and brain, and because it shares tetrapod biology with human. Understanding how axolotls regenerate complex tissues may reveal mechanisms to activate stem cells within human tissues to organize and reform damaged tissues. Beyond regeneration, the axolotl presents many untapped disease models that were identified and rigorously examined with traditional developmental approaches before the genetics/genomics era. With our recent development of the first chromosome-scale assembly of the axolotl genome, these and new models that will be created in coming years through genome editing, can be advanced for the first time to significantly impact biomedical research. However, to advance these models, improvements of the genome assembly are needed along with new datasets to enable genome-wide studies of the large axolotl genome. To accomplish these objectives, we propose three specific aims. In Aim 1, we will resolve inter- and intra-specific variation within the current assembly and resolve complex repetitive regions that have hampered the placement of ~6 Gb of the 32 Gb genome. Specifically, we will employ a powerful trio binning strategy that takes advantage of long read sequencing of DNA from axolotl x tiger salamander (A. tigrinum) hybrids. This approach leverages decades of experience in generating interspecific hybrids to resolve assembly gaps/errors and accurately place gene models within their non-coding regulatory environments. Additionally, we will analyze sequence data from 10 AGSC axolotls from branches of the pedigree that optimally sample laboratory genetic diversity. In Aim 2, we will perform Chip-Seq to identify changes in histone post-translational modifications during tail and limb regeneration. Characterization of epigenetic marks for embryo, larval, and adult models of regeneration will provide new resources for regeneration research and advance community efforts in performing genome wide studies. Aim 3 will address significant community needs, user-friendly access to large scale genomic datasets and improvement of genomic and bioinformatic capabilities of investigators in the axolotl community. Accomplishment of these aims will significantly advance axolotl as an animal model for biomedical research.