Signalling mechanisms in cell survival and cell growth

对生死的控制和生物学中的任何问题一样至关重要。细胞的生存和生长是由解释细胞内外信号以改变其活动的机制控制的。近年来，控制细胞死亡的过程已经变得非常清楚。最近，帮助细胞生存和生长的细胞功能被认为是相互依存的。在我们的实验室里，我们研究了常见的果蝇，它们的基因与人类的相似性远远超出了我们的想象。它是研究细胞生物学这一方面的理想模式生物。 在我的实验室开放之前，我证明了极低的AKT水平会导致整个果蝇胚胎细胞死亡。AKT是胰岛素受体的目标蛋白。从那时起，我们发现AKT的一个靶点FOXO在解释低水平的胰岛素受体信号方面是关键，并能抑制果蝇的生长和改变新陈代谢。最重要的是，我们发现FOXO在营养缺乏的饥饿条件下可能提供一种有限的生存机制。奇怪的是，FOXO可能在感知营养的可获得性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，包括果蝇中的唐氏综合症基因迷你脑。在未来，我们将发现AKT、迷你脑和FOXO的更多靶点，并评估它们在细胞生存和生长中的作用。 由于细胞死亡在神经元退化中起作用，我们研究了蛋白质诱导果蝇神经变性的细胞学基础。我们正在研究Parkin和PINK1这两个在某些遗传形式的帕金森病中存在缺陷的基因在抵消有毒蛋白质导致的细胞死亡方面的作用。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。

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.