Transcriptional control of gene expression during the G2-M phase of the cell cycle

真核细胞分裂成两个子细胞是受到协调调控的。这种分裂过程在酵母菌中需要1小时，在人类中需要长达24小时。在这段时间里，一系列事件在称为细胞周期的过程中启动，一个事件导致另一个事件，最终导致细胞分裂，然后重新启动整个过程。为了调节这一过程，细胞周期中有许多控制点。其中一个主要的控制点是DNA复制之后和细胞分裂之前(G2-M控制点)。这个控制点至少在转录水平上受到部分调控，转录水平是基因被启动、其密码被破译并转化为第一个RNA和蛋白质的过程。这个项目旨在研究这个关键控制点的转录是如何调控的。我们将使用模式生物酿酒酵母(发芽酵母)，它显示出与人类等高等生物相比，细胞周期控制机制具有显着的保守性。我们知道在这个控制点起作用的关键调节因子(转录因子)，以及它们本身是如何通过被称为磷酸化的过程进行修饰来调节的。然而，我们不知道转录因子是如何调控转录的。此外，我们不知道在这个控制点上如何发生微妙的不同激活事件。也就是说，并不是所有的基因都以相同的时间动力学被激活。我们的目标是研究转录因子如何发挥功能来调节靶基因转录的分子细节，以及这些转录因子本身是如何控制的。我们预计，我们在模型系统中所做的发现将与其他系统直接相关。事实上，细胞周期调控的放松是肿瘤发生的先决条件，因此我们的研究可能会影响我们对癌症的理解和抗击癌症的能力。

The division of eukaryotic cells into two daughter cells is coordinately regulated. This division process takes from between 1 hour in yeasts to up to 24 hours in humans. Over this period a series of events is initiated in a process called the cell cycle whereby one event leads to another, and ultimately culminates in cell division and then reinitiation of the whole process. To regulate this process, there are numerous control points in the cell cycle. One of the major control points is following DNA replication and before the cells commit to division (the G2-M control point). This control point is at least partially regulated at the level of transcription, the process by which genes are turned on and their code deciphered and converted to first RNA and the protein. This project aims to study how transcription at this key control point is regulated. We will use the model organism S. Cerevisiae (budding yeast) which shows a remarkable conservation of cell cycle control mechanisms with higher organisms such as humans. We know the key regulators (transcription factors) that act at this control point, and how they themselves can be regulated through modification by a process known as phosphorylation. However, what we do not know is how the transcription factors regulate transcription. Furthermore, we do not know how subtly different activation events occur at this control point. ie not all genes are activated with the same temporal kinetics. We aim to study the molecular details of how transcription factors function to regulate target gene transcription and how these transcription factors are themselves controlled. We anticipate that the findings we make in our model system will be directly relevant to other systems. Indeed the deregulation of cell cycle control is a pre-requisite for tumourigenesis, therefore our studies may impact on our understanding of and ability to combat cancer.