Molecular architecture of myelin - the roles of intrinsically-disordered myelin basic proteins

大脑是人体最复杂的器官，可分为灰质和白质。白质由髓磷脂组成，富含脂质，形成膜。髓鞘是包裹在中枢神经系统（CNS）轴突（神经）周围的膜状螺旋，使它们能够有效地传递冲动。中枢神经系统髓磷脂是由被称为少突胶质细胞的细胞膜的延伸形成的——一个少突胶质细胞可以包裹几种不同的神经纤维。髓磷脂的形成是一个复杂的过程，分阶段发生。在每个阶段，必须严格控制基因表达，以产生适量的许多不同成分，然后需要将这些成分运送到细胞中的正确位置。即使在成熟的大脑中，髓磷脂蛋白和脂质也在不断地更新和补充。当我们在电子显微镜下观察髓磷脂时，我们看到的主要是致密髓磷脂，但也有不太致密的环区。更仔细的观察表明髓磷脂由不同的“微域”组成，可以通过洗涤剂的生化提取“解剖”出来。这些不同类型的微结构域不仅在其组成蛋白和脂质的组成上有所不同，而且在这些蛋白质在合成后如何被不同的酶修饰（最后一个过程称为“翻译后修饰”）。我们的研究旨在了解中枢神经系统髓磷脂蛋白的修饰模式如何在发育过程中动态变化，以及正常成人髓磷脂的空间变化。我们使用各种生化，生物物理和细胞生物学工具来做到这一点，并为本科生和研究生提供学术和技术培训。

The brain is the most complex organ in the body and can be subdivided into gray and white matter. White matter is formed by myelin, and is highly enriched in lipids forming a membrane. The myelin sheath is a membranous spiral that wraps around the axons (nerves) of the central nervous system (CNS), and enables them to transmit impulses efficiently. The CNS myelin is formed by extensions of membranes of cells called oligodendrocytes - one oligodendrocyte can enwrap several different nerve fibers. The formation of myelin is a complex process that occurs in stages. At each stage, gene expression must be strictly controlled to produce the right amounts of many different components that then need to be delivered to the correct location in the cell. Even in the mature brain, there is constant turnover and replenishment of myelin proteins and lipids. When one looks at myelin in the electron microscope, one sees mainly compact myelin, but also less compact loop regions. An even closer look indicates that myelin consists of different "microdomains" that can be "dissected" out by biochemical extractions with detergents. These various types of microdomains differ both in composition of their constituent proteins and lipids, but also in how these proteins have been modified by different enzymes after synthesis (this last process is called "post-translational modification"). Our research aims to understand how the modification pattern of CNS myelin proteins varies dynamically during development, and spatially in normal adult myelin. We use a variety of biochemical, biophysical, and cell biological tools to do so, and provide scholarly and technical training for undergraduate and graduate students.