The role of PKC in chromatin structure and gene regulation

多细胞生物体中的细胞已经发展出了感知局部环境并以适当方式做出反应的机制。特别是，它们需要对体内其他细胞产生的信号或环境损伤做出反应。细胞已经发展了信号传导通路，将信号从细胞外围传递到细胞的其余部分。这些途径的一个主要目的地是细胞核。在这里，这些通路靶向被称为转录因子的关键分子开关。通过磷酸化修饰转录因子，它们的活性被改变，这改变了它们解开遗传密码的能力，改变了整个基因组的表达。本项目将研究包含重要蛋白PKC的信号通路如何控制细胞中基因的表达。PKC是重要的，因为它直接感知细胞表面的完整性。我们将使用酵母作为一个简单的模式生物，因为这是很容易操作。重要的是，PKC在人类中是保守的，因此我们在酵母中学到的东西可以对我们对人类生理学和疾病的理解产生直接影响，正如我们以前对不同酵母信号蛋白的工作所证明的那样。由于PKC是制药公司正在开发药物的目标，我们的研究结果可能对理解这些药物如何发挥作用具有重要意义，因此有助于指导它们用于治疗心脏病和癌症等人类疾病。

Cells within multicellular organisms have developed mechanisms for sensing their local environment and responding in an appropriate manner. In particular, they need to respond to signals produced by other cells in the body or to environmental insults. Cells have developed signalling pathways to transmit signals from the cell periphery to the rest of the cell. One major destination for these pathways is the nucleus. Here the pathways target key molecular switches known as transcription factors. Through the modification of the transcription factors by a process known as phosphorylation, their activity is altered, and this changes their ability to unlock the genetic code and alter the expression of whole cohorts of genes. This project will investigate how one signalling pathway containing the important protein PKC functions in controlling the expression of genes in the cell. PKC is important as it directly senses the integrity of the cell surface. We will use yeast as a simple model organism as this is easily manipulatable. Importantly, PKC is conserved in humans so things that we learn in yeast can have immediate impacts on our understanding of human physiology and disease as exemplified by our previous work on different yeast signalling proteins. As PKC is a target which drug companies are developing drugs against, our findings are likely to have important implications for understanding how these drugs might act and hence help in directing their use in treating human ailments such as heart disease and cancer.