Liver disease now kills more people in the UK than ever before, and roughly 4% of the population already show signs of ongoing liver damage. This project tackles a fundamental gap: while doctors know that a person’s genetic makeup strongly influences whether they develop liver disease, the specific genes responsible remain largely unknown. The researchers will screen mice carrying random DNA mutations, then challenge them with drugs, alcohol, or a high-fat diet to mimic the real-world triggers that push a susceptible liver into disease. This approach lets them spot which mutations make the liver vulnerable—and which genes protect it. If successful, the work will produce two concrete outcomes: a list of genes that drive liver damage, and a set of new mouse models that mimic human liver disease. Those models can then be used by other scientists to test potential treatments before they reach patients. This is fundamental biology with a clear translational path—identifying the genetic switches that turn a healthy liver into a diseased one, and giving researchers the tools to flip them back.
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Liver disease is now the 5th most common cause of death in the United Kingdom and about 4% of the population have evidence of ongoing liver damage. It is important to find out more about the causes of liver disease so that new treatments can be developed or to prevent liver damage occurring. This project aims to help us unravel some of the complex biology behind liver disease so that we can develop and evaluate new treatments in the future. It is clear that many factors contribute to the development of liver disease in patients and one of those factors is their genetic background. We will identify contributory genes by taking mice with random mutations in their DNA and screening for liver abnormalities. As liver disease may occur when a susceptible person is challenged with a drug, alcohol or by being overweight we will use the challenges to increase the sensitivity of our screening programme. Therefore, in addition to identifying the most important genes which cause liver disease we will also develop mouse models of liver disease which could be used for testing new treatments.
Ann Daly (Co-Investigator)Christopher Day (Co-Investigator)David Jones (Co-Investigator)Howard Thomas (Principal Investigator)John Iredale (Co-Investigator)Kevin Park (Co-Investigator)Mark Thursz (Co-Investigator)Quentin Anstee (Co-Investigator)Robert Goldin (Co-Investigator)Robert Johnson (Co-Investigator)Roger Cox (Co-Investigator)Stephen Brown (Co-Investigator)Stuart Forbes (Co-Investigator)
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