POZ-ZF Transcription Factors in Signal Transduction and Development.

POZ-ZF 信号转导和发育中的转录因子。

• 批准号: RGPIN-2020-06822
• 负责人: Daniel, Juliet
• 金额: $ 4.23万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741455
• 关键词: POZ; ZF; Transcription; Factors; Signal

The development of multicellular organisms involves a highly coordinated and controlled series of events that regulates the proliferation and differentiation of cells into tissues and organs with specific functions. These events require communication between cells via a phenomenon called signal transduction, which often culminates in the nucleus with changes in gene expression controlled by proteins called transcription factors. These changes in gene expression in turn trigger cells to respond and either divide, differentiate, become motile or die. Although several signaling pathways have been identified that regulate the crucial stages of early vertebrate development, it remains unclear how these various signals are integrated to elicit the specific cellular responses needed during development, and to ensure a health viable organism/vertebrate. One unique family of transcription factors (POZ-zinc finger, POZ-ZF) have been linked to signaling pathways that are essential for vertebrate development. These transcription factors interact with each other and regulate numerous target genes. Data from my laboratory revealed that frog embryos lacking different POZ-ZF proteins displayed striking early and late developmental defects. These observations led to our hypothesis that POZ-ZF proteins are important downstream effectors of signaling transduction during early vertebrate development. Since little is known about how POZ-ZF proteins are mechanistically connected to established signaling pathways, our Discovery research program focuses on deciphering "The Role and Basic Mechanisms of Action of POZ-ZF Transcription Factors in Vertebrate Development" using cell lines and the frog Xenopus laevis as a model organism. Xenopus is a proven model system for such studies because frogs are inexpensive, the embryos are very easy to manipulate for protein knockdown and overexpression studies, and the Xenopus versions of the mammalian POZ-ZF proteins we are studying are very similar. To achieve our research goals, we will utilize a variety of cutting-edge and established molecular cell biology and genetic techniques, and functional assays. Experimentally linking POZ-ZF proteins to established developmental signaling pathways and morphogenetic events would provide novel insight on the crosstalk between signaling pathways in early vertebrate development. Our findings would also add to the knowledge base of POZ-ZF protein function in vertebrates, and significantly advance our knowledge and understanding of fundamental developmental processes that are shared by all vertebrates. My Discovery research program is designed to train, mentor and produce at least seven highly qualified personnel (3 MSc/PhD, 3 BSc) with competitive research, critical thinking and communication skills; skills that are essential for successful careers in the Canadian and International Research & Development arena.

多细胞生物体的发育涉及一系列高度协调和受控的事件，这些事件调节细胞增殖和分化成具有特定功能的组织和器官。这些事件需要细胞之间通过一种称为信号转导的现象进行交流，这种现象通常在细胞核中达到高潮，基因表达的变化由称为转录因子的蛋白质控制。这些基因表达的变化反过来触发细胞做出反应，要么分裂，分化，变得能动或死亡。尽管已经鉴定了几种调节早期脊椎动物发育的关键阶段的信号传导途径，但仍不清楚这些各种信号是如何整合的，以引起发育期间所需的特定细胞反应，并确保健康的活生物体/脊椎动物。 一个独特的转录因子家族（POZ-zinc finger，POZ-ZF）与脊椎动物发育所必需的信号通路有关。这些转录因子相互作用并调节许多靶基因。来自我实验室的数据显示，缺乏不同POZ-ZF蛋白的青蛙胚胎显示出明显的早期和晚期发育缺陷。这些观察结果导致我们的假设，POZ-ZF蛋白是重要的下游效应的信号转导在早期脊椎动物的发展。 由于对POZ-ZF蛋白如何与已建立的信号通路机械连接知之甚少，我们的发现研究计划侧重于使用细胞系和青蛙非洲爪蟾作为模式生物来破译“POZ-ZF转录因子在脊椎动物发育中的作用和基本作用机制”。非洲爪蟾是一个经过验证的模型系统，因为青蛙是廉价的，胚胎是非常容易操纵的蛋白质敲低和过表达的研究，和非洲爪蟾版本的哺乳动物POZ-ZF蛋白，我们正在研究的是非常相似的。为了实现我们的研究目标，我们将利用各种尖端和成熟的分子细胞生物学和遗传技术，以及功能测定。 通过实验将POZ-ZF蛋白与已建立的发育信号通路和形态发生事件联系起来，将为早期脊椎动物发育中信号通路之间的串扰提供新的见解。我们的发现也将增加POZ-ZF蛋白在脊椎动物中功能的知识基础，并显着推进我们对所有脊椎动物共有的基本发育过程的知识和理解。我的发现研究计划旨在培养，指导和产生至少七名高素质的人员（3个硕士/博士，3个理学士），具有竞争力的研究，批判性思维和沟通技能;在加拿大和国际研究与发展竞技场成功职业所必需的技能。