Grant: Operating Grant

The cells within the tissues of an organism must obey controls that tell them when to divide, and importantly, when to stop. These controls are present from the early stages in the embryo, when most tissues are being formed, right up to the adult. One of the hallmarks of cancer is the inability to correctly respond to these controls and many of the genes that dictate these decisions have been found to be altered in malignant tumours. Using a simple model organism called C. elegans my laboratory has uncovered how some of these genes regulate cell division in a simple organ, the intestine. This gives us a simplified model to understand how these mutated genes may also affect tumour growth. By first generating mutants that have abnormal cell divisions in the intestine, we can determine what genes are mutated to cause the observed defects. One of these mutations occurs in a gene involved in driving cell multiplication, and mutant forms of the human gene are associated with aggressive tumours in the head, neck, breast and lung. Other mutants we have obtained show defects in the correct integrity of cell divisions that occur later during the formation of the intestine and the genes that are affected in these mutants include an important inhibitor of tumour formation that is mutated in most cancers, although how it works is still misunderstood. Another series of mutated genes we identified are critical for silencing the expression of many genes required for animal growth. We want to find out how, and with whom, these genes act to control the proliferation and growth of these cells. By better understanding how these genes function, we hope to reveal novel targets around which therapeutic strategies can be developed to fight the growth of cancerous cells in a more specific manner.