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

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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.