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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717874
• 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进行交流和协调它们的活动。从胚胎阶段开始，细胞选择分裂以创建新细胞，获得细胞身份或在称为程序性细胞死亡的过程中自毁。这些决定在很大程度上由蛋白质控制，这些蛋白质启动称为信号转导或信号传导的级联事件。来自邻近细胞的环境触发或信号可以启动信息传递，这些信息传递到细胞核，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。我的研究小组使用特征明确的遗传上顺从的果蝇，果蝇，作为模式生物。我们对一组称为蛋白激酶的酶特别感兴趣，这些酶将磷酸基团添加到靶蛋白或底物上。由于这种添加的磷酸盐，可以改变底物的活性。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，由于细胞的功能和形状正在发生动态变化，因此这种调节蛋白质活性的瞬时方式是必不可少的。20多年来，我们开展了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，重点是胚胎发生模式，眼睛发育和肢体形成（腿和翅膀）。在这个建议中，我们描述了我们的两种蛋白质命名为Wallenda和Cdk 8的特性，并提出实验，以揭示他们如何控制细胞的生存或死亡，以及他们如何促进发展。 我们的方法是基础性的，或基于发现的研究，旨在了解细胞功能在生物体发育过程中是如何调节的。这将与研究跨物种这些过程的广泛科学家群体相关，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种结果。首先，我们将在同行评审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。我们预计这些研究将产生2-4篇研究出版物。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，我们将参与科学推广交流，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生物体发育的理解，而且还将为HQP提供优秀的本科和研究生培训机会。这些HQP将学习有价值的和多样化的技能，使他们能够加入加拿大的劳动力队伍，并加强研究，教学和创新。