Observing how Hsp90 affects the aggregation of Amyloid-B in C. elegans as a model for Alzheimer's Disease
Lead Research Organisation:
University of Leeds
Department Name: Sch of Molecular & Cellular Biology
Abstract
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.
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.
