Every hour, in every one of your cells, 1,000 building blocks of your DNA are damaged simply because your body is warm. The Genome Damage and Stability Centre studies the molecular repair crews that fix this constant barrage of genetic wear and tear. This matters because when those repair systems fail, the consequences are stark: damaged instructions can be passed to children, causing genetic disease, or mutations can accumulate in individual cells, leading to cancer. People with inherited faults in DNA repair develop cancers at rates more than 1,000 times higher than the general population. The Centre brings together physicists, biologists, and clinicians to understand exactly how these repair proteins work and what goes wrong in disease. This is primarily fundamental science—understanding the core machinery that keeps our genomes stable. The Centre is not promising a cure tomorrow. But by pinpointing the precise molecular defects in cancer-prone patients, the work lays the groundwork for more rational cancer therapies. It also trains a new generation of scientists who can translate these insights into clinical practice, and it is building a tumour tissue bank with a local hospital to bridge the gap between the lab bench and the patient bedside.
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Our genomes are made up of long DNA molecules that contain the genetic blueprint that tells every part of our body how to function. This vast reference library, which contains all the instructions that both allowed us to grow from an egg to an adult and dictates every function of our everyday lives, is continually being damaged. One example is our skin cells. The genome in these cells is constantly damaged by sunlight. Another is our intestines: our intestinal cells? genomes are damaged by carcinogens in food. In all our cells, simply by existing at body temperature, our genomes are constantly being damaged, at the rate of 1000 bases (the building blocks of our genomes) every hour in every cell. Fortunately, our cells contain sophisticated mechanisms for protecting our genomes by repairing all this damage. It is these protection processes that are the focus of the work of the Genome Damage and Stability Centre. If these repair mechanisms stop working properly, there are two possible consequences. First, genetic damage (i.e. wrong instructions) can be passed on to our offspring. This could cause a genetic disease. Second, individual cells in our body can start losing information and accumulating permanent genetic changes (mutations). When this happens, cancer can result. The Centre enables scientists of different disciplines to work together and benefit from each other?s expertise. Our work ranges from studies on the protein molecules that repair DNA inside cells, the genes that are altered in cancer cells through to investigations on cancer-prone people. Part of our research is the study of several genetic diseases in which one of the DNA repair systems is faulty. This results in the affected individuals having very high incidences of cancer, more than 1000 times higher than in the general population. By discovering the nature of the defects in people with these disorders, we are able not only to help diagnose and hopefully cure these conditions, but also to gain general insights into how cancers can arise. Over the next five years, as well as continuing our basic research, we will strengthen our links with clinicians by developing joint training programs and establishing a cancer tissue bank in collaboration with the cancer centre at the local hospital. Our work will help ultimately to design more rational cancer therapies.
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