Regulation of Drosophila development by protein kinases

复杂生物体的发展需要细胞进行交流和协调其活动。从胚胎阶段开始，细胞选择分裂以创造新细胞，获得细胞身份，或者在被称为程序性细胞死亡的过程中自毁。这些决定在很大程度上是由蛋白质决定的，这些蛋白质启动了一系列称为信号转导或信号的事件。来自邻近细胞的环境触发或信号可以启动传递到细胞核的信息，以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组如何发育成专门的成人组织。我的研究小组使用了一种具有良好特征的遗传顺从果蝇--黑腹果蝇，作为一个模式生物。我们特别感兴趣的是一组被称为蛋白激酶的酶，它将磷酸基团添加到目标蛋白质或底物上。由于添加了这种磷酸盐，底物的活性可以改变。这种调节是暂时的，可以通过去除磷酸盐来逆转。在发育过程中，随着细胞功能和形态的动态变化，这种调节蛋白质活性的瞬时方式是必不可少的。20多年来，我们一直在进行NSERC资助的工作，以研究一些蛋白激酶如何发挥作用，以确保果蝇的正常发育，重点是胚胎发育、眼睛发育和肢体形成(腿和翅膀)。在这项提案中，我们描述了两种名为Wallenda和CDK8的蛋白质的特征，并提议进行实验，以揭示它们如何控制细胞的存活或死亡，以及它们如何促进发育。 我们的方法是基础的，或基于发现的研究，试图了解细胞功能在有机体的发育过程中是如何调节的。由于我们研究的所有蛋白激酶在多细胞生物体中在进化上是保守的，这将与广泛的跨物种研究这些过程的科学家相关。 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，旨在接触到广泛的发育生物学、遗传学和信号转导受众。我们预计这些研究将产生2-4种研究出版物。我们将通过海报和演讲等会议演示来传播我们的成果。此外，我们将进行科学外展交流，分享我们的研究成果，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有机体发育的理解，还将为HQP在本科生和研究生层面提供出色的培训机会。这些HQP将学习有价值的和多样化的技能，这些技能将使他们能够加入加拿大的劳动力大军，并加强研究、教学和创新。

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.