Mechanisms modulating cell identity in regenerative mammalian epithelia

项目总结： 意义：我们的组织经常受到伤害、感染和疾病的损害。中国的许多器官 人体在受损后可以进行自我修复，以恢复其功能。这一复苏已经完成 通过成体干细胞的作用，生成不同类型的新细胞来取代受损材料。 成体干细胞修复组织的能力使它们成为发展的吸引人的靶点 恢复因受伤或衰老而受损的组织的健康的疗法。然而，还有很大一部分 未知干细胞后代如何采用适当的细胞命运来重新填充组织。这条通向 独立奖提案寻求了解在体内产生特定细胞类型的机制 可再生的哺乳动物组织。 候选人和环境：独立之路奖的候选人卡拉·麦金利博士是 致力于领导细胞生物学和再生医学领域的独立研究小组。 麦金利博士在麻省理工学院伊恩·奇斯曼博士的实验室接受了细胞生物学和生物化学方面的培训，在那里 她发现了组装和调节细胞分裂机制所需的机制。在此期间 在加州大学旧金山分校著名细胞生物学家罗恩·维尔博士的实验室进行博士后研究，她已经开发出 有机物质长期活体成像的方法，这是一种模仿 体外器官的细胞组成、结构和反应。如本提案所述， 她将应用她的有机体成像方法，结合定义信号的有针对性的应用，以 了解外在提示如何改变两个高度再生组织中的细胞特性：小肠(目标1)， 和子宫内层(子宫内膜；目标2)。 职业发展：在指导期间，应聘者将获得额外的小鼠遗传学培训 将她的发现从体外有机系统转化为体内环境，并在生殖生物学中 将她的方法从小肠器官移植到子宫内膜器官。结合对这一问题的研究 小肠和子宫内膜为她的独立小组提供了一个独特而强大的应用平台 揭示更新的统一特征以及确定关键方面的常用工具和方法 器官特有的生理学。候选人将与老鼠遗传学和生殖生物学方面的专家在 加州大学旧金山分校建立必要的科学技能来推动她在这两个互补模型中的研究。她会的 她还接受了一整套培训，以支持她的职业发展。这项提案的执行将 为候选人配备强大的技能和强大的平台，以启动她的独立研究计划。

PROJECT SUMMARY: Significance: Our tissues experience frequent damage from injuries, infections and disease. Many organs in the human body can undergo self-repair to restore their function after damage. This recovery is accomplished through the actions of adult stem cells, which generate new cells of diverse types to replace damaged material. The capacity of adult stem cells to repair tissues makes them an appealing target for the development of therapies to restore the health of tissues that have been impaired by injury or aging. However, much remains unknown about how stem cell progeny adopt appropriate cell fates to repopulate tissues. This Pathway to Independence Award proposal seeks to understand the mechanisms that generate specific cell types in regenerative mammalian tissues. Candidate and environment: The candidate for this Pathway to Independence Award, Dr. Kara McKinley, is committed to leading an independent research group at the interface of cell biology and regenerative medicine. Dr. McKinley was trained in cell biology and biochemistry in the laboratory of Dr. Iain Cheeseman at MIT, where she uncovered mechanisms required for the assembly and regulation of the cell division machinery. During her postdoctoral studies at UCSF in the laboratory of renowned cell biologist Dr. Ron Vale, she has developed approaches for long-term live imaging of organoids, which are “mini-organ” culture systems that mimic the cellular composition, architecture and responses of organs outside of the body. As described in this proposal, she will apply her organoid imaging approaches, combined with the targeted application of defined signals, to understand how extrinsic cues alter cell identity in two highly regenerative tissues: the small intestine (Aim 1), and the uterine lining (endometrium; Aim 2). Career development: During the mentored period, the candidate will gain additional training in mouse genetics to translate her findings from in vitro organoid systems into in vivo contexts, and in reproductive biology to translate her approaches from small intestinal organoids to endometrial organoids. Combining studies of the small intestine and the endometrium presents a unique and powerful platform for her independent group to apply common tools and approaches to reveal unifying features of regeneration, as well as to identify key aspects of organ-specific physiology. The candidate will work with experts in mouse genetics and reproductive biology at UCSF to build the necessary scientific skills to propel her research in these two complementary models. She will also undertake a suite of training to support her professional development. The execution of this proposal will equip the candidate with a formidable skillset and a robust platform to launch her independent research program.