The Burmese Python as a Model System for the Study of Metabolism and Organ Regeneration

缅甸蟒蛇作为代谢和器官再生研究的模型系统

• 批准号: 10042881
• 负责人: Nima Saeidi
• 金额: $ 27.94万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10042881
• 关键词: Animal Model; Atlases; Atrophic; Biogenesis; Biological Models; Blood Circulation; Burmese; Cell Nucleus; Clinical; Communication; Comparative Study; Critical Illness; Data; Data Set; Development; Diabetes Mellitus; Disease; Distal; Exposure to; Fasting; Foundations; Funding Opportunities; Gastric Bypass; Gene Expression; Gene Expression Profiling; Genetic Transcription; Glucose; Growth; Habits; Health; Heart; Heart Diseases; Heart Hypertrophy; Heart failure; Home environment; Homeostasis; Hour; Human; Institutes; Institution; Intestinal Bypasses; Intestinal Neoplasms; Intestines; Laboratories; Malignant Neoplasms; Mammals; Mediating; Metabolic; MicroRNAs; Modeling; Molecular; Mus; Nutrient; Obesity; Organ; Organ Size; Pathologic; Pathologic Processes; Pathway interactions; Pattern; Phase; Physiological; Process; Pythons; Regression Analysis; Regulation; Reptiles; Research; Research Personnel; Resolution; Resources; Rodent; Role; Sampling; Signal Transduction; Small RNA; Starvation; Stimulus; Study models; Technology; Testing; Therapeutic; Time; Tissues; United States National Institutes of Health; Untranslated RNA; adverse outcome; comparative; deep sequencing; effective therapy; fascinate; feeding; functional adaptation; genome annotation; heart dimension/size; heart function; improved; innovation; insight; interest; metabolic abnormality assessment; multidisciplinary; novel; obesity treatment; organ growth; organ regeneration; pressure; programs; rapid growth; response; transcriptome sequencing; transcriptomics

PROJECT SUMMARY In this project, we will study Burmese pythons (BPs), a natural paradigm of rapid, massive, controlled and recurring organ growth. Several studies have shown that unlike laboratory mammals and humans, the BPs naturally feed infrequently, and their feeding habits are associated with rapid and massive regulatory responses and organ growth, which is followed by a postdigestion regression phase. This unique model can provide valuable insights about the underlying adaptive, beneficial, well-orchestrated growth and regression cellular regulatory programs and how they differ from the uncontrolled processes of cancer and the various maladaptive hypertrophic or atrophic disease states. In the proposed studies, we hope to develop a deeper mechanistic understanding specifically about intestinal adaptation. By studying the growth phase in the immediate post-feeding period, we can discover those mechanisms that drive the gut and the other organs so efficiently and rapidly from dormancy to full function. The analysis of the regression phase will provide us with valuable information about the mechanisms, which may act as a “brake” and halt growth. This project builds upon and expands our preliminary comparative studies of rodents, pythons and humans, which have revealed conserved intestinal signatures and key regulatory networks. Comparative studies between species are powerful and the discovery of common, evolutionary conserved mechanistic targets, processes and pathways provide further confidence on the significance of the findings. The differences may represent opportunities to harness, for therapeutic benefits by trying to recapitulate in mammals, for example, the transcriptomic patterns that are different in BPs. Our data highlight the role of microRNAs (miRNAs), which are small non-coding RNAs that regulate gene expression at the post-transcriptional level. They are excellent candidates for mediating the plasticity of the intestinal adaptive processes, as they are master regulators of gut homeostasis and many functions. In addition, because miRNAs can be secreted in the circulation, they are ideally suited to serve as a mode of communication between the gut and distal tissues. In the first specific aim, we seek to define a signature of dynamically regulated miRNAs that parallels the growth and regression of the intestine in BPs and mice. In the second specific aim, we will develop a high-resolution cellular atlas of the intestinal transcriptomic changes that are associated with the growth-regression cycles in BPs. We propose a novel, transformative project that brings together cutting-edge technologies, a team of multidisciplinary investigators and a fascinating new animal model system, which could shift current research paradigms and expand current research models, because of the numerous scientific and practical advantages it offers. It will enable and set the foundations for further mechanistic studies, while it will generate unique information, resources and valuable datasets. We anticipate that the interest in this model will grow, given the recent developments (e.g., annotation of the genome), its increasingly appreciated advantages and the interest by the lay public.

项目摘要 在这个项目中，我们将研究缅甸蟒蛇（BPS），这是一种自然的快速，巨大，控制和 恢复器官生长。 自然会很少喂食，他们的喂养习惯与快速和大规模的调节有关 响应和器官生长，然后是消化后回归阶段。 就基本的适应性，有益，良好的增长和回归提供宝贵的见解 蜂窝监管程序及其与Canceses Sand Tourious的不受控制的过程有何不同 适应性肥大或萎缩性疾病状态。 通过研究您的生长阶段，专门了解肠道适应性。 立即喂养后期，我们可以发现那些驱动其他器官的机制 从休眠到完整功能的有效和迅速的回归阶段分析将为我们提供 有关该机制的宝贵信息，该机制可能是“制动器”并停止增长 在并扩大了我们的啮齿动物，python和人类的前期。 物种之间的比较研究是比较研究物种是对比较研究 强大并发现了共同的，进化保守的机械目标，过程和途径 对发现的重要性提供了进一步的信心。 线束，试图用哺乳动物概括治疗益处，例如转录组模式 BPS不同的数据突出了MicroRNA的作用（miRNA） 调节基因表达的RNA在转录后水平。 介导肠道自适应过程的塑料，作为肠内稳态的主要调节剂 还有许多功能。 在第一个特定目的中，我们。 定义动态调节的miRNA的签名 BPS和小鼠在第二个特定目标中 与BPS中的生长回归周期相关的转录组变化。 变革性项目带来了托格特尖端技术，这是一个多学科研究人员的团队 以及一个引人入胜的新动物模型系统，可以改变当前的研究范例并扩大当前 研究模型，由于它提供的众多科学和实践优势。 进一步的机械研究的基础，同时将产生独特的信息，资源和 鉴于最近的发展，我们预计该模型的兴趣将增长 基因组的注释）越来越多地赞赏外行公众的利益。