Regulation of Drosophila development by protein kinases

蛋白激酶对果蝇发育的调节

• 批准号: RGPIN-2020-06192
• 负责人: Verheyen, Esther
• 金额: $ 3.64万
• 依托单位: Simon Fraser 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=741084
• 关键词: Regulation; Drosophila; development; protein; kinases

Development of complex organisms requires that cells communicate and coordinate their activities. Starting from the embryonic stages, cells choose between dividing to create new cells, acquiring a cellular identity, or self-destructing in a process called programmed cell death. These decisions are largely governed by proteins that initiate a cascade of events termed signal transduction or signaling. Environmental triggers or signals from neighboring cells can start a relay of information that travels to the nucleus to influence the expression of genes that encode proteins and shapes cell behaviour. The long-term goal of my research program is to understand how groups of cells develop into specialized adult tissues. My research group uses the well-characterized genetically amenable fruit fly, Drosophila melanogaster, as a model organism. We are particularly interested in a group of enzymes called protein kinases which add phosphate groups onto target proteins, or substrates. As a result of this added phosphate, the activity of the substrate can be altered. This kind of regulation is temporary and can be reversed by removing the phosphate. During development, as cells are undergoing dynamic changes in their function and shape, such a transient way to regulate protein activity is essential. For over 20 years we have carried out NSERC-funded work to examine how a number of protein kinases function to ensure proper Drosophila development, with a focus on embryogenic patterning, eye development and limb formation (legs and wings). In this proposal we describe our characterization of two proteins named Wallenda and Cdk8 and propose experiments to reveal how they control whether cells survive or die and how they contribute to development. Our approach is fundamental, or discovery-based, research which seeks to understand how cell function is regulated during the development of an organism. This will be of relevance to a broad group of scientists studying these processes across species, since all the protein kinases we study are evolutionarily conserved in multi-cellular organisms. We anticipate that these studies will result in several outcomes. First, we will publish our research findings in peer-reviewed journals aimed at reaching a broad developmental biology, genetics and signal transduction audience. We expect these studies to give rise to 2-4 research publications. We will disseminate our results through conference presentations such as posters and talks. Furthermore, we will engage in science outreach communication to share our findings and teach the general public the power of model organism research. This research will not only expand our understanding of organismal development, but it will also provide outstanding training opportunities to HQP at the undergraduate and graduate level. These HQP will learn valuable and diverse skills that will position them to join the workforce in Canada and enhance research, teaching and innovation.

复杂生物体的发育需要细胞之间的交流和协调。从胚胎阶段开始，细胞在分裂产生新细胞，获得细胞身份，或在称为程序性细胞死亡的过程中自我毁灭之间做出选择。这些决定在很大程度上是由蛋白质控制的，这些蛋白质启动了一系列被称为信号转导或信号传导的事件。来自邻近细胞的环境触发或信号可以启动信息传递，传递到细胞核，影响编码蛋白质和塑造细胞行为的基因的表达。我的研究计划的长期目标是了解细胞群如何发育成专门的成人组织。我的研究小组使用具有良好特征的遗传适应性的果蝇（Drosophila melanogaster）作为模式生物。我们对一组被称为蛋白激酶的酶特别感兴趣，它们将磷酸基团添加到目标蛋白质或底物上。由于添加了磷酸盐，底物的活性可以被改变。这种调节是暂时的，可以通过去除磷酸盐来逆转。在细胞发育过程中，由于细胞的功能和形态发生了动态变化，因此这种瞬时调节蛋白质活性的方式是必不可少的。20多年来，我们一直在进行nserc资助的工作，研究蛋白质激酶如何发挥作用，以确保果蝇的正常发育，重点是胚胎发育模式，眼睛发育和肢体形成（腿和翅膀）。在这篇论文中，我们描述了两种名为Wallenda和Cdk8的蛋白质的特征，并提出了实验来揭示它们如何控制细胞的生存或死亡以及它们如何促进发育。我们的方法是基于发现的基础研究，旨在了解生物体发育过程中细胞功能是如何调节的。这将与跨物种研究这些过程的广大科学家群体相关，因为我们研究的所有蛋白激酶在多细胞生物中都是进化保守的。我们预计这些研究将产生几个结果。首先，我们将在同行评议的期刊上发表我们的研究成果，旨在达到广泛的发育生物学，遗传学和信号转导受众。我们期望这些研究能发表2-4篇研究论文。我们将通过海报和讲座等会议展示来传播我们的成果。此外，我们将参与科学外展交流，分享我们的发现，并向公众传授模式生物研究的力量。这项研究不仅将扩大我们对组织发展的理解，而且还将为HQP的本科生和研究生提供优秀的培训机会。这些HQP将学习有价值的和多样化的技能，这将使他们加入加拿大的劳动力队伍，加强研究、教学和创新。