Paul Nurse

Cell Cycle Laboratory

The goals of our laboratory are to better understand the global cellular networks which regulate the eukaryotic cell cycle, cell form and cell growth. These cellular controls are fundamental to the growth, development and reproduction of all living organisms. They are also relevant to understanding disease particularly cancer. Unrestricted cell proliferation during cancer is often associated with altered cell cycle and cell growth controls, and shape changes are associated with metastatic cells when they are escaping their tissue of origin and migrating elsewhere in the body.

The model organism used for these studies is the genetically amenable single celled eukaryote, the fission yeast Schizosaccharomyces pombe. This organism has been extensively developed for experimental investigations, and powerful genetic, genomic, biochemical, chemical and cell biological resources and methodologies are available for its study. It has a well characterised cell cycle and a regular cylindrical cell shape, which makes it ideal for studies of cell form and of overall cell growth.

There are many detailed accounts of the molecular mechanisms that underlie specific aspects of eukaryotic cell biology. However, how these molecular mechanisms act together more globally at the higher levels of the cell or of major sub-cellular components such as organelles are not so well understood. For example, progression through the cell cycle is often coordinated with cell growth so the onset of S-phase and mitosis occur at critical cell sizes, but it is not clear how cells monitor their volume or mass and integrate this information with cell cycle progression. An example at the organelle level is the nucleus, which is of a defined size and is usually located centrally in the cell, but the mechanisms ensuring nuclear position and size remain unclear.

Gene transcription and protein translation are crucial for cell growth but how the overall rates of these processes are determined in each individual cell is also unknown. Another example is the global regulation of origin firing along chromosomes during DNA replication. How such global cellular controls operate will be revealing about the mechanisms cells use to determine properties such as their size, linear dimensions, and intracellular position. This will involve investigating the complex networks of gene functions and the range of regulatory inputs and outputs of the control under study including the effects of variability on the transfer of information through these networks. There is a particular interest in the roles of the CDKs and their regulatory networks in controlling cell cycle transitions.

The experimental approaches used are based on the wide range of methodologies available for fission yeast. The laboratory has been involved in the development of a number of these methodologies including molecular genetics, genomics, whole genome gene deletion resources and more recently chemical biology approaches. Given the significant conservation of controls between yeasts and metazoans, studies of fission yeast will also lead to improved understanding of equivalent controls in human cells.

An important aim of the laboratory is to train and develop researchers in the methods and reasoning necessary to investigate complex problems of molecular and cellular biology. The specific projects are broadly based, and researchers joining the laboratory are encouraged to develop a project based on them or to develop something new. These projects lend themselves to multidisciplinary approaches as indicated by the range of techniques and procedures to be utilised. Each researcher is responsible for their own project and is encouraged to take their project away with them when they start up their own laboratory. Applications are encouraged from researchers who have not previously worked with fission yeast as any experimental training required is provided.

Selected publications

Gutierrez- Escribano, P and Nurse, P (2015) A single cyclin-CDK complex is sufficient for both mitotic and meiotic progression in fission yeast. Nature Communications. In Press.

Kaykov, A. Nurse,P. (2015) The spatial and temporal organization of origin firing during S phase of fission yeast. Genome Research. In Press.

Wu PY, Nurse P. Replication origin selection regulates the distribution of meiotic recombination. Mol Cell. 2014;53(4):655-62

Hayles J, Wood V, Jeffery L, Hoe KL, Kim DU, Park HO, Salas-Pino S, Heichinger C, Nurse P. A genome-wide resource of cell cycle and cell shape genes of fission yeast. Open Biol. 2013;3(5):130053

Kawashima SA, Takemoto A, Nurse P, Kapoor TM. A Chemical Biology Strategy to Analyze Rheostat-like Protein Kinase-Dependent Regulation. Chem Biol. 2013;20:262-71

Wood E, Nurse P. Pom1 and cell size homeostasis in fission yeast. Cell Cycle. 2013;12(19)

Kawashima S, Takemoto A, Nurse P, Kapoor TM. Analyzing fission yeast multi-drug resistance mechanisms to develop a genetically tractable model system for chemical biology. Chem Biol. 2012;19 893-901

Navarro FJ, Nurse P. A systematic screen reveals new elements acting at the G2/M cell cycle control. Genome Biol. 2012;13: R36

Nurse P, Hayles J. The cell in an era of systems biology. Cell. 2011;144(6):850-4

Castagnetti, S, Oliferenko, S, Nurse, P. Fission yeast cells undergo nuclear division in the absence of spindle microtubules. PLoS Biol. 2010;8:e1000512

Coudreuse D, Nurse P. Driving the cell cycle with a minimal CDK control network. Nature. 2010;468:1074-9

Kim DU, Hayles J, Kim D, Wood V, Park HO, Won M, Yoo HS, Duhig T, Nam M, Palmer G, Han S, Jeffery L, Nurse P, Hoe KL. Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe. Nat Biotechnol. 2010;28(6):617-23

Zhurinsky J, Leonhard K, Watt S, Marguerat S, Bahler J and Nurse P. A coordinated global control over cellular transcription Current Biology. 2010;20:2010-5

Moseley JB, Mayeux A, Paoletti A, Nurse P. A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature. 2009; 459:857-60

Wu, PY, Nurse, P. Establishing the program of origin firing during S phase in fission yeast. Cell. 2009;136:852 - 864

Neumann FR. Nurse P. Nuclear size control in fission yeast. J Cell Biol. 2007;179:593-600

Paul Nurse

Paul.Nurse@crick.ac.uk
+44 (0)379 62495

  • Qualifications and History
  • 1973 PhD, University of East Anglia, UK
  • 1984 Imperial Cancer Research Fund (ICRF)  Group leader at Lincoln's Inn Fields (ICRF became Cancer Research UK in 2002
  • 1989 Professor of Microbiology at University of Oxford, UK
  • 1996 Director General of ICRF
  • 2002 Chief Executive Cancer Research UK
  • 2003 President of the Rockefeller University, USA
  • 2010 Director of the Francis Crick Institute