Mechanisms of tubule interconnection

项目摘要 在这一赠款转移请求中，我们的目标是继续我们的工作，定义调解的信号和机制 新形成的肾单位与肾集合系统的连接。定义肾小管的机制 互连仍然不完全理解，并且对于移植iPScell衍生的肾脏至关重要 类器官或其它干细胞衍生的肾脏替代组织。这段时间将致力于完成 我们的研究受体，配体和信号转导途径，介导侵入细胞行为和小管 互连.以成年斑马鱼的再生肾为模型，我们将 使用功能缺失突变体、荧光转基因报告基因和组织原位标记的组合 侵入以定义小管互连的基本信号和效应物。 PI，Iain Drummond博士，已经将他的实验室搬到了荒岛山生物实验室， 戴维斯老龄化和再生中心的教授和主任。调动的原因 MDI生物实验室是基础肾脏研究的历史所在地，特别是 霍默·史密斯和弗兰克·爱泼斯坦对肾脏进化和上皮细胞的深刻和开创性的研究的网站 运输2)MDI生物实验室已经发展成为NIH衰老和再生卓越研究中心， 专注于使用遗传模式生物的基础研究，这与Drummond实验室的重点一致， 斑马鱼再生Drummond博士担任MDIBL COBRE赠款的PI职位， 继续并扩大他指导年轻调查人员的作用。3)在他的领导下，MDIBL获得了新的， 尖端的显微镜设备（蔡司980双光子共聚焦显微镜），将使新的生活 成像方法来研究小管相互连接，并进一步开发了单细胞RNA测序能力， 可以完成肾脏再生研究4)MDIBL致力于支持PI，学生， 博士后，将提高实验室的生产力，并提供更长期的稳定性。5)正在进行的合作 杰克逊实验室的MDI将使鱼类研究转化为肾脏移植的小鼠模型。的 PI的职业计划是继续领导斑马鱼肾脏发育和再生领域， 翻译发育机制和修复途径的基础研究，以解决人类AKI问题， CKD。

PROJECT SUMMARY In this request for grant transfer, we aim to continue our work defining the signals and mechanisms that mediate connection of newly formed nephrons to the kidney collecting system. Defining mechanisms of tubule interconnection remains incompletely understood and will be essential for engrafting iPScell derived kidney organoids or other stem cell derived kidney replacement tissue. This grant period will be devoted to completing our study of receptors, ligands, and signal transduction pathways that mediate invasive cell behavior and tubule interconnection. Focusing on the regenerating kidney in adult zebrafish as a model of nephron addition, we will use a combination of loss of function mutants, fluorescent transgene reporters, and in situ markers of tissue invasion to define essential signals and effectors of tubule interconnection. The PI, Dr. Iain Drummond, has moved his lab to the Mount Desert Island Biological Laboratory to take on the position of Professor and Director of the Davis Center for Aging and Regeneration. The reasons for the transfer of institution are: 1) The MDI Biological Laboratory is a historical seat of fundamental kidney research, notably the site of Homer Smith's and Frank Epstein's insightful and seminal studies on kidney evolution and epithelial transport. 2) MDI Bio Lab has evolved to be an NIH Center of Research Excellence in Aging and Regeneration, focusing on fundemental studies using genetic model organisms which aligns with the Drummond lab's focus on zebrafish regeneration. Dr. Drummond assumed the position of PI on the MDIBL COBRE grant allowing him to continue and expand his role mentoring young investigators. 3) Under his directorship MDIBL has obtained new, cutting-edge microscopy equipment (Zeiss 980 two photon confocal microscope) that will enable new live imaging approaches to tubule interconnection studies and further developed single cell RNA seq capabilies that will allow completion of kidney regeneration studies. 4) MDIBL has committed support for the PI, students, and a Postdoc that will increase lab productivity and provide more long term stability. 5) Ongoing collaborations with the Jackson Lab on MDI will enable translation of fish studies to mouse models of kidney engraftment. The career plans of the PI are to continue to lead the field in zebrafish kidney development and regeneration and translate fundamental studies of developmental mechanisms and repair pathways to address human AKI and CKD.