Functions of Heparan Sulphate in the C. elegans Nervous System

我的研究目的是在分子水平上了解神经系统的发育。我特别感兴趣的是一组复杂的糖蛋白，硫酸乙酰肝素蛋白多糖(HSPGs)。我的研究使用线虫秀丽线虫作为一个简单的遗传模型。了解神经元的发育是生物学中的基本问题之一，因为神经元控制着从运动到自主功能(如心跳和呼吸)的行动，以及我们的感觉、思维和记忆能力。成年人的大脑有超过1000亿个神经元，每个神经元平均与1000个靶细胞连接，但错误很少发生。神经元在发育过程中的迁移和神经元连接的形成是由基因决定的，并决定了整个神经系统的连接，但其分子机制仍然知之甚少。HSPG存在于细胞膜和细胞间的胞外间隙中。热休克蛋白G介导细胞与环境的相互作用，在调节发育和动态平衡方面发挥关键作用。在神经系统中，HSPG引导迁移的神经元及其过程，并控制涉及学习和记忆的功能。线虫含有与人类神经发育有关的关键基因的同源基因。一个简化的模型有望提高对正常蜂窝通信中HSPG的理解。了解正常发育将为癌症、阿尔茨海默氏症和帕金森氏症等退行性神经元疾病以及损伤后再生的机制提供新的见解。

My research is aimed at understanding the development of the nervous system at the molecular level. I am particularly interested in a group of complex glycoproteins, heparan sulphate proteoglycans (HSPGs). My research uses the nematode Caenorhabditis elegans as a simplistic genetic model. Understanding neuronal development is one of the fundamental questions in biology as neurons control actions from movement to autonomous functions such as heart beat and breathing, and our ability to sense, think and remember. The adult human brain has over hundred billion neurons which each make connections with an average of 1000 target cells, yet mistakes happen very rarely. Neuron migration and formation of neuronal connections during development are genetically determined and dictate the wiring of the entire nervous system, yet the molecular mechanisms are still poorly understood. HSPGs are present in cell membranes and in the extracellular space between cells. HSPGs mediate interactions of cells with their environment and play critical roles in regulating development and homeostasis. In the nervous system HSPGs guide migrating neurons and their processes, and control functions involved in learning and memory. C. elegans contains homologues of key genes involved in human neuronal development. A simplified model is expected to improve understanding of HSPGs in normal cellular communication. Understanding normal development will provide novel insights into mechanisms that underlie cancer, degenerative neuronal diseases such as Alzheimer’s and Parkinson’s, and regeneration after injury.