Investigating CDK control of the eukaryotic cell cycle

About the project

About the Project A 2027 Crick PhD project with Paul Nurse. Project background and description The cell cycle is the process by which all cells reproduce. It underpins the growth and development of all organisms and plays a key role in cancer when cell reproduction goes out of control. Cyclin Dependent Kinases (CDKs) are the major regulators of the eukaryotic cell cycle, controlling onset and progression through S-phase and mitosis. CDKs underpin the temporal order of these cell cycle events and also act as the ‘pacemakers’ determining the rate of progression through the cell cycle. The research project is concerned with understanding how CDKs are regulated and function to bring about these controls. The fission yeast will be used for these studies. It is a powerful model for such investigations and was one of the organisms in which CDKs were discovered. Each of the fission yeast 5000 genes have been deleted and screened, identifying around 500 genes required for cell cycle progression including CDKs and their regulators. CDK consists of three components, the protein kinase CDK, the cyclin regulator, and a less studied CKS component. The CDK activity is regulated by an inhibitory Wee1 tyrosine protein kinase and an activatory Cdc25 phosphatase. Around 300 proteins are phosphorylated in vivo by CDKs and are dephosphorylated by 4 specific phosphatases. This forms the background for the project. The aim of the research project is to investigate how CDK acts as the cell cycle pacemaker. It will examine how the level of CDK activity rises during the cell cycle to bring about onset of S-phase and mitosis, how this is co-ordinated with cell growth, and which substrates are phosphorylated and when that occurs during the cell cycle. There will be a particular emphasis on CDK activity located within the cell nucleus which acts as the pacemaker. The Laboratory has proposed that chromatin acts as a platform for CDK regulation and function and this will be investigated in the future. This is relevant because many cell cycle events are associated with chromatin including S-phase and aspects of mitosis. In addition, DNA cell cycle checkpoints are likely to be associated with chromatin and are known to work through CDKs. The research project is broadly scoped to give choice to the PhD student as to which particular aspects they wish to investigate during their doctorate studies. A wide range of approaches are available for the work including genetics, molecular biology, cell biology, proteomics, phosphoproteomics, and advanced microscopy. The Laboratory fosters a lively, friendly and supportive environment for students to learn and develop as a researcher. The Laboratory consists of about 10 researchers, including graduate students, post-doctoral researchers, and laboratory research scientists, and provides a very supporting working environment. Candidate background This project would suit candidates with an interest in fundamental cell biology problems. They could have a background in molecular biology, cell biology or genetics and should like working with and helping other laboratory members. All training in techniques and methods will be provided. Lab-specific question Science advances with unusual and creative ideas based on experimental data. Do you have examples of such ideas that you have had even if may turned out be incorrect.

Research areas