CAREER: Instruction in Neuroscience and Research Toward Characterization of a Novel Family of Potassium Channel Related Proteins

T.Perney9876321钾离子通道是孔状结构，它允许钾离子以一种调节的方式通过细胞膜。它们对所有细胞都很重要，但在心脏、肌肉和神经细胞中起着特别关键的作用，它们控制着电信号的模式。通道由包含亚单位的四个孔域组装而成。这种组装是由通道的一个区域介导的，该区域被称为NAB或Ti结构域。我们已经确定了一类新的蛋白质，称为NABS，它包含一个类钛结构域，但不包含孔结构域。一种称为双杂交相互作用陷阱的分子生物学方法与经典的生化技术相结合，将被用来确定NAB蛋白中的钛结构域是否介导蛋白质-蛋白质组装，如果是，则识别结合伙伴。其中一种NAB蛋白的表达水平已被证明受到细胞因子的促进，细胞因子是参与调节正常发育和损伤后炎症反应的分子。不同NAB的基因表达谱将通过原位杂交和免疫学技术在正常脑发育期间、脑损伤后以及对细胞因子的反应中进行检测。综上所述，这些研究将增加我们对钛结构域结构功能关系的理解，也可能为深入了解NAB蛋白的功能作用，包括任何潜在的参与细胞对损伤的反应。高中生、本科生和研究生将积极参与项目的开发和实施。此外，促进批判性思维的战略将被纳入三门重新设计的课程，以加强对分子和神经科学及其对社会的影响的了解。还将扩大对当地小学的外联计划，以促进将科学发现过程纳入科学课程。

T. Perney9876321Potassium channels are pore-like structures, which allow the flux of potassium ions across a cell's membrane in a regulated manner. They are important for all cells, but have a particularly critical role in heart, muscle, and nerve cells where they control the pattern of electrical signaling. The channels are formed by the assembly of four pore domain containing subunits. This assembly is mediated by a region of the channel, which has been termed the NAB or Ti domain. We have identified a new class of proteins, termed Nabs, which contain a Ti-like domain, but no pore domain. A molecular biological approach called the two hybrid interaction trap coupled with classic biochemical techniques will be used to determine whether the Ti domain in the Nab proteins mediate protein-protein assembly and if so, to identify the binding partners. The expression levels of one of the Nab proteins has been shown to be increased by cytokines, molecules involved in mediating both normal development and the inflammation response after injury. Gene expression profiles for the different Nabs will be examined by in situ hybridization and immunological techniques during normal brain development, after brain injury, and in response to cytokines. Taken together, these studies should increase our understanding of the structure function relationships of Ti domains and may also provide insight into the functional role of Nab proteins including any potential involvement in the cellular response to injury. High school, undergraduate and graduate students will actively participate in development and performance of the project. In addition, strategies to promote critical thinking will be incorporated into three redesigned courses to enhance the understanding of Molecular and Neurosciences and their impact on society. An outreach program to local elementary schools will also be expanded to promote the inclusion of the scientific discovery process in the science curriculum.