Novel enzymes in brain lipid metabolism

大脑中含有大量不同类型的特殊脂肪。大脑中存在多少脂肪、在哪里发现脂肪以及脂肪的类型不同，都会影响大脑的工作方式，甚至可能导致阿尔茨海默氏症和抑郁症等疾病的发展。人体使用称为酶的微小机器来制造这些脂肪，并控制脑细胞对它们的处理。我们对其中一些酶了解很多，但对其他酶却知之甚少。我研究的目的是发现控制大脑脂肪使用的新脑酶，并解释它们的作用和如何做到这一点。这项研究将有助于我们了解大脑是如何工作的，也将为治疗脑部疾病提供新的靶点。这在老龄化人口中尤其重要，就像我们今天在加拿大看到的那样，那里痴呆症等脑部疾病的患病率正在稳步上升。为了进行这项发现工作，我们首先寻找大脑中丰富的小酶机器。然后，我们复制他们的DNA蓝图，并用这些蓝图来欺骗在塑料培养皿中生长的细胞制造大量的酶。我们可以提纯这种酶，并将其用于试管实验，以确定它是否真的对脂肪起作用，并测试它喜欢哪种脂肪，以及它对这些脂肪有什么作用。为了测试这在大脑功能方面的意义，我们接下来让小鼠缺乏脑细胞中的这种酶。根据受影响的脑细胞的类型，这可能会改变大脑功能的不同方面，从学习所需的神经元的分支，到帮助将信号从身体的远端传递到大脑中心的保护性髓鞘的形成。从这一基础发现工作中产生的知识将形成了解大脑在健康和疾病中如何工作的基础。

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.****