Studying a new faulty gene that cause heart muscle disease

The role of ALPK3 in autosomal dominant hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is an inherited heart disease that can lead to life-threatening heart rhythm problems and sudden cardiac death. It is normally caused by genetic mistakes, or mutation, that alter tiny structures in the heart called sarcomeres. These structures normally help heart cells to contract. But not all people with HCM have a known genetic mistake, which suggests other unknown genes that cause this disease must exist. Dr Gehmlich’s team have evidence that a gene called ALPK3 could be a culprit in HCM, but little is known about what it specifically does. This project aims to understand the role of ALPK3 in the heart, by identifying which molecules it interacts with and whether ALPK3 regulates them. They will also study one of the mutations in ALPK3 found in people with HCM. Specifically, they will engineer the mutation into stem cells, and then induce the cells to become heart muscle cells that contract, to see what problems arise.. They will also engineer a mouse to carry the same mutation. Both models will reveal what goes wrong in heart cells when ALPK3 is faulty and could be used to test whether drugs commonly used to treat HCM will work in people with this genetic mistake.