Advancement of the Xiphophorus Model for Studying Disease

研究疾病的剑尾动物模型的进展

• 批准号: 10669550
• 负责人: Caitlin Gabor
• 金额: $ 73.35万
• 依托单位: TEXAS 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: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669550
• 关键词: Access to Information; Affect; Alleles; Animal Housing; Animal Husbandry; Animal Model; Animals; Area; Automobile Driving; Backcrossings; Behavior; Biological; Biological Models; Biology; Biomedical Research; Cancer Etiology; Cells; Chromosomes; Chronobiology; Communities; Complex; Consult; Control Locus; Country; Data; Development; Diagnosis; Discipline; Disease; Disease Progression; Disease model; Distant; Embryology; Endocrinology; Ensure; Epigenetic Process; Etiology; Exhibits; Experimental Models; Fishes; Fresh Water; Future; Gene Expression; Genes; Genetic; Genetic Drift; Genetic Epistasis; Genetic Variation; Genome; Genomics; Genotype; Goals; Health; Histocompatibility; Human; Hybrids; Immunology; Improve Access; Inbreeding; Institution; International; Knowledge; Laboratories; Lead; Malignant Neoplasms; Metabolic Diseases; Mission; Modeling; Molecular; Obesity; Optics; Organ; Orthologous Gene; Outcome; Parasitology; Phenotype; Physiology; Play; Population; Positioning Attribute; Procedures; Production; Publications; Publishing; Quantitative Trait Loci; Regulation; Research; Research Personnel; Research Training; Resources; Role; Selection for Treatments; Services; Signal Transduction; Study models; System; Texas; Tissues; Toxicology; Training; Translational Research; United States National Institutes of Health; Universities; Variant; Xiphophorus; animal resource; bioinformatics tool; candidate identification; cell type; disease diagnosis; disease phenotype; functional genomics; gene interaction; genetic pedigree; genetic resource; genetic variant; genome resource; genomic locus; human disease; human model; improved; innovation; medical specialties; model development; model organism; molecular phenotype; novel; novel therapeutic intervention; nutrition; obesity development; operation; personalized medicine; preservation; student training; therapeutic development; trait; transcriptomics; translational model; tumor progression; tumorigenesis

Project Summary Xiphophorus fishes serve as long-standing biomedical models for translational research in multiple disciplines. They are used widely in research topics that connect to the missions of multiple NIH Institutions/Centers. Xiphophorus fish exhibit several features that no other animal model shares, including high level of inter-species genetic divergence, capability of producing inter-species hybrids and backcross hybrids, adaptive phenotypes representing human diseases. Recently accomplished genome assemblies for several Xiphophorus species, in addition to the specialties of Xiphophorus model, provide the premise to study non-biased assessment of genetics underlying complex traits associated with diseases in humans. The primary goal of the Xiphophorus Genetic Stock Center (XGSC) is to maintain these unique features and preserve the strength of this model to be used in biomedical research. The XGSC is not only a resource center hosting many different species, but also the only center that preserves/maintains high level of tractable genotypic and phenotypic diversity. The XGSC maintains 61 pedigreed lines that belong to 24 Xiphophorus species. It resides at Texas State University and has actively served a broad research community since 1993. XGSC has a wide international impact. We provide pedigreed fish and material to investigators in 30 laboratories of 11 countries. Herein this proposal, we focus on continuing successful operation of the XGSC, enhancing animal husbandry, maintaining relevant resources, and providing animal husbandry training for the research community, and student training for the host institution. Proposed enhancement of Xiphophorus resources will leverage the disease-like phenotypes related to cancer, metabolic disorders and the human disease-associated molecular phenotypes. Innovatively, we will investigate on the cellular, tissue and organ level, the genetic signaling underlying (a) cancer progression and (b) metabolic disorder/obesity. We will achieve theses goal by characterizing cell types involved in these phenotypes on the molecular level which are critically involved in driving disease progression and by deciphering epigenetic alterations during disease development. We will also (c) characterize alleles that contribute to metabolic disorder formation. In addition, we will (d) expand disease related resources of Xiphophorus by studying molecular traits that are associated with various types of human diseases, with a primary goal of identifying molecular traits that can benefit early disease diagnosis and treatment. The significance of achieving the goals in the proposal will be the support to continue to maintain irreplaceable genetic resources and advancing our understanding on the molecular, cellular and organismic level of genetic interactions associated with human health and diseases. The outcomes of the proposal can forward our understanding of disease etiology, lead to novel therapeutic strategies, and identify causal or regulatory alleles that may be utilized as predictors and targets in personalized medicine.

项目摘要 Xiphophorus鱼类是多个转化研究的长期生物医学模型 学科。它们被广泛用于连接多个NIH任务的研究主题 机构/中心。 Xiphophorus鱼具有几个其他动物模型共享的功能， 包括高种间遗传差异，产生种间杂种的能力和 反向交叉杂种，代表人类疾病的自适应表型。最近完成的基因组 除Xiphophorus模型的专业外，几种Xiphophorus物种的组装还提供了 研究与疾病相关的遗传学基础遗传学的无偏见评估的前提 人类。 Xiphophorus遗传储备中心（XGSC）的主要目标是维持这些独特的 特征并保留该模型的强度，以用于生物医学研究。 XGSC不仅是 资源中心拥有许多不同的物种，但也是唯一保持/保持高水平的中心 可处理的基因型和表型多样性。 XGSC保持61条属于24 Xiphophorus物种。它居住在德克萨斯州立大学，并积极提供了广泛的研究 自1993年以来的社区。XGSC具有广泛的国际影响力。我们提供血统的鱼类和材料 11个国家的30个实验室的调查人员。在此提案中，我们专注于继续成功 XGSC的操作，增强畜牧业，维持相关资源并提供 研究社区的畜牧培训和主持人的学生培训。 提议的增强Xiphophorus资源将利用与疾病样的表型相关的 癌症，代谢疾病和与人类疾病相关的分子表型。创新，我们 将在细胞，组织和器官水平上研究（a）癌症进展的遗传信号传导 （b）代谢障碍/肥胖。我们将通过表征涉及的细胞类型来实现这些目标 在分子水平上的表型与驱动疾病进展和通过 疾病发育过程中的表观遗传改变。我们还将（c）表征等位基因 有助于代谢障碍形成。此外，我们将（d）扩大与疾病相关的资源 通过研究与各种类型的人类疾病相关的分子性状，与xiphophorus 确定可以使早期疾病诊断和治疗有益于分子特征的主要目标。这 实现该提案目标的意义将是继续保持不可替代的支持 遗传资源并促进我们对分子，细胞和生物水平的理解 与人类健康和疾病有关的遗传相互作用。提案的结果可以 转发我们对疾病病因的理解，导致新的治疗策略，并确定因果关系 可以用作个性化医学的预测因子和靶标的监管等位基因。