Supervised morphogenesis in gastruloids (SUMO)

原肠胚的监督形态发生 (SUMO)

• 批准号: 10053130
• 金额: $ 82.5万
• 依托单位: IMPERIAL COLLEGE LONDON
• 依托单位国家: 英国
• 项目类别: EU-Funded
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10053130
• 关键词: Supervised; morphogenesis; gastruloids; SUMO

The lack of realistic in vitro organ models that can faithfully represent in vivo physiological processes is a major obstacle affecting the biological and medical sciences. The current gold standard is animal experiments, but it is increasingly clear that these models mostly fail to recapitulate the human physiology. Moreover, animal experiments are controversial, and it is a common goal in the scientific community to minimize the use of animals to a strictly necessary minimum. The emergence of stem cell engineered organ models called organoids represents the only viable alternative to animal research. However, current organoid technology is yet to produce the larger physiologically relevant organ models that the medical sciences really need. Specifically, current organoids are too small, not vascularized and lack the 3-dimensional organization found in vivo. In this interdisciplinary project we aim to challenge all these limitations by using the recently developed gastruloid technology guided by cutting edge bioengineering and artificial intelligence. Gastruloids are formed by initiating the very early developmental processes and develops along a highly coordinated three axial process that closely resembles mammalian embryogenesis. Moreover, gastruloids can develop several organ precursors simultaneously and thus constitutes important improvements over conventional single-tissue organoids. To harvest the potential of gastruloid technology we will first implement large sequencing and imaging experiments to optimize the developmental trajectory of gastruloids for organ inductions. We will then build these datasets into a multimodal data matrix to identify gastruloid candidates for cardiovascular and foregut development. Specifically, we will identify candidates that show strong vasculogenesis as candidates for later vascularisation by anastomose with endothelial cells.

缺乏可以忠实地代表体内生理过程的体外器官模型是影响生物学和医学科学的主要障碍。当前的黄金标准是动物实验，但越来越明显的是，这些模型主要无法概括人类的生理学。此外，动物实验是有争议的，在科学界，将动物的使用降至最低的最低限度是科学界的一个普遍目标。干细胞工程器官模型的出现称为类器官，代表了动物研究的唯一可行替代方案。但是，当前的类器官技术尚未产生医学科学真正需要的更大的生理相关器官模型。具体而言，当前的类器官太小，没有血管化，并且缺乏体内发现的三维组织。在这个跨学科项目中，我们旨在通过使用最新的生物工程和人工智能指导的最近开发的胃lul虫技术来挑战所有这些局限性。通过启动非常早期的发育过程并沿高度协调的三个轴向过程形成胃类似，与哺乳动物的胚胎发生非常相似。此外，胃底子可以同时发展几个器官前体，因此构成了与常规单根组织器官相比的重要改进。为了收获胃固醇技术的潜力，我们将首先实施大型测序和成像实验，以优化胃诱导的发育轨迹，以进行器官诱导。然后，我们将将这些数据集构建到多模式数据矩阵中，以识别用于心血管和前肢开发的胃候选物。具体而言，我们将确定表现出强血管生成的候选者，作为后来通过内皮细胞吻合的血管化的候选者。