Grant: Operating Grant

The form that cancers take can be extremely varied, ranging from solid tumours that can affect almost any part of the body, to the overgrowth of blood cells. These differences are related mainly to the origins of the cancer cells. However, regardless of its origin cancer is fundamentally the result of unrestricted growth. It was recognized many years ago that, to improve the effectiveness of cancer treatments, we need to understand how cells regulate their growth and what exactly goes wrong with this process in cancer. Each cell uses a complex network of signals in order to decide how rapidly it should grow. Our work aims to understand this growth network and how it is changed in cancer cells. The ribosome, the large and complex "machine" that makes all the proteins of the cell, is at the heart of this network. Manufacture of the ribosome requires many hundreds of components and is an endeavour that occupies between 50 and 80% of the cell's efforts. We have found that growth factors, oncogenes and tumor suppressors directly control ribosome manufacture. Further, bottle-necks in production of ribosomes cause a range of degenerative diseases, but have been also been correlated with an inability to activate the most important tumour suppressors. Our aim is to understand how the earliest steps of the manufacture of ribosomes occur and how this relates to cancer and other diseases.