Exploring Wnt-Fzd signaling specificities

项目摘要 我们正在申请资金，以购买基于荧光的细胞分选器，BioRad S3E，用于 筛选纳米体库及鉴定和分离与细胞高亲和力结合子的目的 转导Wnt信号的表面蛋白。 WNT蛋白代表着一类重要的发育信号，具有不同的功能 都是后生动物物种。放松对WNT信号的管制可能会产生灾难性的后果， 包括胚胎致死、出生缺陷和疾病。Wnt的特异性和选择性靶向研究 信号转导在再生医学和癌症治疗中具有巨大的治疗潜力。 此外，由于其在发育和干细胞中的多种和强大的活性，Wnt蛋白 作为细胞和组织工程的有力工具，前景看好。 我们研究的长期目标是更好地了解Wnt蛋白和 它们的下游信号事件影响细胞命运的决定，从而推动 专门针对WNT信号的技术和治疗。为此，我们开发了 一种创新的技术，它利用了经过工程设计的Wnt激动剂，称为WNT模拟，它展示了 与天然Wnt蛋白相比，具有更好的生化特性。使用我们之前开发的 和出版的WNT模拟，称为F7L6，作为指导，我们建议开发一个这样的集合 WNT激动剂，每种设计用于结合和激活不同类型的WNT受体。这个 所要求的仪器将能够鉴定和分离新的高亲和力粘结剂和 加快发展WNT模拟新技术。 这项拟议的研究将大大推进干细胞研究和组织领域的发展。 通过建立新的工具和方法在体外和体外操纵Wnt信号来实现工程 活着。由于它在人类疾病和疾病中的丰富作用，更好地理解WNT 信号转导对于开发治疗目前不治之症的新疗法至关重要。

Project Summary We are requesting funds to purchase a fluorescence-based cell sorter, the BioRad S3E, for the purpose of screening nanobody libraries and identifying and isolating high affinity binders to cell surface proteins that transduce Wnt signals. Wnt proteins represent an important class of developmental signals with diverse functions across all metazoan species. Deregulation of Wnt signaling can have catastrophic consequences, including embryonic lethality, birth defects, and disease. Specific and selective targeting of Wnt signaling has great therapeutic potential in regenerative medicine and the treatment of cancer. Additionally, with their diverse and potent activities in development and stem cells, Wnt proteins hold great promise as potent tools in cell and tissue engineering. The long-term objective of our research is to gain a better understanding of how Wnt proteins and their downstream signaling events influence cell fate decisions, and thereby advance technologies and treatments that specifically target Wnt signaling. To this end, we have developed an innovative technology that utilizes engineered Wnt agonists, called Wnt mimetics, which exhibit superior biochemical properties compared to native Wnt proteins. Using our previously developed and published Wnt mimetic, called F7L6, as a guide, we propose to develop a collection of such Wnt agonists, each designed to engage and activate distinct types of Wnt receptors. The requested instrument will enable the identification and isolation of novel high affinity binders and accelerate the development of novel Wnt mimetics. The proposed research will significantly advance the field of stem cell research and tissue engineering by establishing new tools and methods to manipulate Wnt signaling in vitro and in vivo. With its abundant roles in human disorders and diseases, a better understanding of Wnt signaling is essential for the development of novel therapies for currently incurable diseases.