Signalling mechanisms in cell survival and cell growth

细胞存活和细胞生长的信号机制

• 批准号: 227932-2009
• 负责人: Staveley, Brian
• 金额: $ 3.64万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570344
• 关键词: Signalling; mechanisms; cell; survival; growth

The control of life and death is as crucial as any question in biology. The survival and growth of cells are controlled by mechanisms that interpret signals from both inside and outside the cell to alter its activity. Over recent years, the processes that control cell death have become very well understood. More recently, the cellular functions that help cells live and grow are being recognised as interdependent. In our laboratory, we study the common fruit fly, the genes of which are far more similar to humans than we once thought. It is an ideal model organism to study this aspect of cell biology. Before opening my lab, I demonstrated that extremely reduced levels of akt a target protein of the insulin receptor, result in cell death throughout the embryonic fruit fly. Since then we have found that a target of akt, foxo, is key in the interpretation of low levels of insulin receptor signalling and acts to inhibit growth and alter metabolism in fruit flies. Most importantly, we have found that foxo may provide a limited survival mechanism during conditions of starvation when nutrients are unavailable. Curiously, foxo may have an important role in sensing the availability of nutrition. In addition, we are investigating other components of insulin receptor signalling including the Down Syndrome gene, minibrain, in flies. In the future, we will identify additional targets of akt, minibrain and foxo and evaluate their roles in cell survival and growth. As cell death plays a role in degeneration of neurons, we investigate the cellular basis of protein induced neurodegeneration in flies. We are studying the effect of the parkin and Pink1, two genes that are defective in some inherited forms of Parkinson disease, in the counteraction of cell death induced by toxic proteins. By increasing the activity of these genes, we have been able to prevent these defects. We are striving to fully understand the biological effects of this process. In summary, our research into the molecular cell biology of fruit flies provides a great opportunity to explore the mechanisms that control the delicate balance between life and death.

对生与死的控制和生物学中的任何问题一样重要。细胞的存活和生长是由解释来自细胞内外的信号以改变其活性的机制控制的。 近年来，控制细胞死亡的过程已经得到了很好的理解。 最近，帮助细胞生存和生长的细胞功能被认为是相互依赖的。 在我们的实验室里，我们研究的是普通的果蝇，它们的基因与人类的相似程度远远超过我们曾经的想象。 它是研究这方面细胞生物学的理想模式生物。 在我的实验室开放之前，我证明了akt（胰岛素受体的靶蛋白）水平的极度降低会导致整个果蝇胚胎的细胞死亡。 从那时起，我们发现akt的一个靶点foxo是解释低水平胰岛素受体信号的关键，它可以抑制果蝇的生长并改变其代谢。最重要的是，我们发现foxo在缺乏营养的饥饿条件下提供了一种有限的生存机制。 奇怪的是，foxo可能在感知营养供应方面发挥着重要作用。 此外，我们正在研究胰岛素受体信号的其他组成部分，包括唐氏综合症基因，迷你脑，在苍蝇。 在未来，我们将确定akt，minibrain和foxo的其他靶点，并评估它们在细胞存活和生长中的作用。 由于细胞死亡在神经元变性中起作用，我们研究了蛋白质诱导的果蝇神经变性的细胞基础。 我们正在研究parkin和Pink1基因的作用，这两个基因在某些遗传性帕金森病中有缺陷，在对抗毒性蛋白诱导的细胞死亡中有作用。 通过增加这些基因的活性，我们已经能够防止这些缺陷。我们正在努力充分了解这一过程的生物效应。 总之，我们对果蝇分子细胞生物学的研究为探索控制生与死之间微妙平衡的机制提供了一个很好的机会。