At the Heart of the Matter
Barth's syndrome is a rare genetic disorder in boys that causes a dangerously weakened heart muscle as well as a weakened immune system. Scientists have discovered that cells from boys with Barth's syndrome cannot properly remodel cardiolipin, the principal phospholipid in heart cells. Phospholipids are fatty compounds essential in maintaining the proper function of cellular membranes; cardiolipin remodelling, which involves the replacement of fatty acids on a cardiolipin molecule with different fatty acids, appear to keep heart cells healthy. Now scientists, like Canada Research Chair Dr. Grant Hatch, wonder whether the reduced ability to remodel cardiolipin may be at the heart of Barth's syndrome.
Hatch is an expert in the field of cardiolipin remodelling in mammalian cells and his lab at the University of Manitoba is one of only a few in the world carrying out this kind of cardiolipin research. He and his colleagues are guided by the belief that their work may lead to new therapies to treat a range of diseases and disorders from Barth's syndrome to cancer.
Currently, Professor Hatch is investigating the role played by a certain gene known as TAZ gene in the metabolism of cardiolipin by examining the phospholipid's regulation and expression in mouse cells. In addition, he is studying the molecular mechanisms in another genetic disorder in humans called congenital generalized lipodystrophy (CGL), which is characterized by a lack of body fat and a tendency to develop insulin resistance and diabetes. His research explores the role of mutations in a particular family of enzymes (called AGPATs) involved in the formation of cardiolipin, enzymes that also figure in the development of diabetes, cancer, atherosclerosis, and obesity.
Hatch is also hard at work exploring the role of cardiolipin regulation in regulating heart cell death (aptosis); he is trying to figure out whether a cell's entrance into aptosis can be prevented or slowed by maintaining the molecular composition of cardiolipin. And, as if all this isn't enough, Hatch is also researching how cardiolipin is synthesized and remodelled during the cell cycle.