Novel enzymes in brain lipid metabolism

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The brain contains high levels of lots of different special types of fat. Differences in how much fat is present in the brain, where it is found, and what types are there, can affect how the brain works, and can even contribute to the development of diseases like Alzheimer's and depression. The body uses tiny machines called enzymes to make these fats, and to control what brain cells do with them. We know a lot about some of these enzymes, but hardly anything about others. The purpose of my research is to discover new brain enzymes that control brain fat use, and to explain what they do, and how they do it. This research will help us to understand how the brain works, and it will also provide new targets for treating brain diseases. This is particularly important in aging populations like we see today in Canada, where the prevalence of brain diseases like dementia are increasing steadily. To do this discovery work, we first search for little enzyme machines that are abundant in the brain. Then, we make lots of copies of their DNA blueprints, and use those to trick cells grown in plastic dishes into making lots of the enzyme. We can purify that enzyme, and use it in test tube experiments to determine whether it really does work on fat, and to test what sorts of fats it prefers, and what it does with them. To test what this means in terms of how the brain functions, we next make mice that lack the enzyme in brain cells. Depending on the sort of brain cell that is affected, this can change different aspects of brain function, from the branching of neurons that is required for learning, to the formation of protective myelin sheaths that help to relay signals from the far reaches of the body to the centre of the brain. The knowledge generated from this fundamental discovery work will form a basis for understanding how the brain works in both health and disease.