Cancer Research UK

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The London Research Institute research groups are based at Lincoln’s Inn Fields and Clare Hall. Our major research themes are: the biology of tumours and tissues, cellular regulatory mechanisms and genomic integrity and cell cycle.

Paul Nurse / Jacqueline Hayles : Cell Cycle

Goals

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 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. 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 plethora of regulatory inputs and outputs of the control under study.

The experimental approaches used are based on the powerful methodologies available for fission yeast, and given the significant conservation of controls between yeasts and metazoans, these studies 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 multi-disciplinary approaches as indicated by the range of techniques and procedures to be utilized. 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.