We are studying how the ‘genome guardian’ p53 protects cells against cancer and using this knowledge to develop more effective treatments for the disease.
Our research centres on a very important gene called TP53, sometimes known as the ‘guardian of the genome.’ TP53 encodes a protein known as p53, which normally helps cells respond to biological emergencies such as DNA damage or stress caused by low oxygen levels.
If a cell’s DNA is badly damaged there is a risk that it can develop into cancer, so p53 activates repair processes that patch up the damage. If cells still continue on the path to becoming cancers, p53 activates a kind of ‘suicide pathway’ that removes faulty cells to protect the rest of the body. But we also now know that p53 helps cells to cope with the less severe stresses and strains of daily life, such as temporary changes in oxygen or nutrient levels.
We are using a range of laboratory techniques to study how p53 normally acts to keep cells functioning correctly and seeing what happens when it doesn’t do its job properly. We are particularly interested in finding out how p53 helps cells respond to changing levels of nutrients known as amino acids, which are the building blocks of proteins, and how alterations in amino acid levels might fuel or prevent tumour growth.
Faults in p53 or its molecular partners have been found in almost all cancers, regardless of where in the body they start. Understanding how this essential gene works in healthy cells and during tumour development will point us towards exciting new avenues for treating cancer more effectively in the future.