Observing how Hsp90 affects the aggregation of Amyloid-B in C. elegans as a model for Alzheimer's Disease

我感兴趣的是淀粉样蛋白B在C. elegans作为阿尔茨海默病（AD）的模型。目的是研究淀粉样蛋白B聚集在何时何地发生，以及热休克蛋白90过表达在这些聚集特征中所起的作用。这种形成可能是无害的，但是如果形成了关键的低聚物核，则发生快速聚合，导致淀粉样蛋白原纤维。这些纤维自组装并形成淀粉样变性的特征性交叉B结构。通过几种机制，存在指数原纤维生长和聚集成淀粉样蛋白-B斑块。在AD中，这些斑块沉积在脑细胞外神经元细胞周围。为了研究体内淀粉样蛋白B聚集的过程及其在变性中的作用，我将与C.其中淀粉样蛋白-B在体壁肌细胞中表达的线虫品系，主要是品系GMC 101和CL 2006。在这种情况下，淀粉样蛋白B聚集并损害运动性，这是一种可以观察到的表型，用于评估变性。聚集之后，我将使用相关的共聚焦显微镜和冷冻电子断层扫描成像的聚集体。通过这项研究，我将在不同的尺度上了解复杂和动态的生物学，从整个生物体到分子结构。

I am interested in Amyloid-B aggregation in the body wall muscle cells and neuronal cells of C. elegans as a model for Alzheimer's Disease (AD). I aim to investigate where and when Amyloid-B aggregation occurs, and what role Hsp90 overexpression plays on these characteristics of aggregation.In disease, Amyloid-B 1-42 can form high order oligomers. This formation can be harmless, however if the critical oligomer nucleus is formed, rapid polymerisation occurs resulting in amyloid fibrils. These fibrils self-assemble and form a cross-B structure, characteristic in amyloidosis. Through several mechanisms, there is exponential fibril growth and aggregation into Amyloid-B plaques. In AD, these plaques are deposited in the brain extracellularly surrounding neuronal cells. This has extracellular effects and circulating Amyloid-B fibrils can enter cells and effect intracellular function.To investigate the process of Amyloid-B aggregation in vivo, and its role in degeneration, I will be working with C. elegans lines in which Amyloid-B is expressed in the body wall muscle cells, primarily lines GMC101 and CL2006. In this case, Amyloid-B aggregates and impairs motility, a phenotype which can be observed to assess degeneration. Subsequent to aggregation, I will image the aggregates using correlated confocal microscopy and cryo-electron tomography. With this research I am to understand complex and dynamic biology at different scales, from the whole organism to molecular structure.