Project overview
One way in which our bodies fight viral infections is to attack viral genomes (either DNA or RNA, depending on the virus) when viruses enter our cells and attempt to replicate. One protein involved in this immune response, APOBEC3A modifies cytosine, one of the four building blocks of DNA and RNA, causing errors (mutations) and breaks in viral genes.
Although APOBEC3A helps to defend us from viral infections, this protection comes at a cost, as we and others have shown that it can turn against our own genes, generating mutations that cause cancer. Not only does APOBEC3A mutate our DNA during cancer development but it appears that APOBEC3A can continue to act in this rogue fashion while patients are receiving chemotherapy; driving drug-resistance and treatment failure. This knowledge has stimulated initiatives to develop APOBEC3A inhibitors; drugs that could block this mutagenic activity in patients. While this approach holds the potential to improve outcomes for millions of cancer patients, it is currently impossible to measure APOBEC3A activity in live cells: a barrier to the
development of APOBEC3A inhibitors.
We will address this problem by establishing a method to visualise and measure APOBEC3A activity in live cells; an advance that crucially, will allow researchers and drug developers to conduct large scale genetic and chemical screens to discover how APOBEC3A is controlled in cells (and therefore how control is lost in cancer cells) and to identify candidate compounds that could be developed into drugs that block APOBEC3A for cancer treatment.
Although APOBEC3A helps to defend us from viral infections, this protection comes at a cost, as we and others have shown that it can turn against our own genes, generating mutations that cause cancer. Not only does APOBEC3A mutate our DNA during cancer development but it appears that APOBEC3A can continue to act in this rogue fashion while patients are receiving chemotherapy; driving drug-resistance and treatment failure. This knowledge has stimulated initiatives to develop APOBEC3A inhibitors; drugs that could block this mutagenic activity in patients. While this approach holds the potential to improve outcomes for millions of cancer patients, it is currently impossible to measure APOBEC3A activity in live cells: a barrier to the
development of APOBEC3A inhibitors.
We will address this problem by establishing a method to visualise and measure APOBEC3A activity in live cells; an advance that crucially, will allow researchers and drug developers to conduct large scale genetic and chemical screens to discover how APOBEC3A is controlled in cells (and therefore how control is lost in cancer cells) and to identify candidate compounds that could be developed into drugs that block APOBEC3A for cancer treatment.
