Matthew D. A. Speed

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During expression of many recombinant proteins, off-pathway association of partially folded intermediates into inclusion bodies competes with productive folding. A common assumption is that such aggregation reactions are nonspecific processes. The multimeric intermediates along the aggregation pathway have been identified for both the P22 tailspike and P22(More)
An unexpected aspect of the expression of cloned genes is the frequent failure of newly synthesized polypeptide chains to reach their native state, accumulating instead as insoluble inclusion bodies. Amyloid deposits represent a related state associated with a variety of human diseases. The critical folding intermediates at the juncture of productive(More)
The misfolding of polypeptide chains and aggregation into the insoluble inclusion body state is a serious problem for biotechnology and biomedical research. Developing a rational strategy to control aggregation requires understanding the mechanism of polymerization. We investigated the in vitro aggregation of P22 tailspike polypeptide chains by classical(More)
The partitioning of partially folded polypeptide chains between correctly folded native states and off-pathway inclusion bodies is a critical reaction in biotechnology. Multimeric partially folded intermediates, representing early stages of the aggregation pathway for the P22 tailspike protein, have been trapped in the cold and isolated by nondenaturing(More)
The failure of newly synthesized polypeptide chains to reach the native conformation due to their accumulation as inclusion bodies is a serious problem in biotechnology. The critical intermediate at the junction between the productive folding and the inclusion body pathway has been previously identified for the P22 tailspike endorhamnosidase. We have been(More)
Recent work in voice synthesis has implemented two-dimensional digital waveguide-mesh models of sound propagation in the vocal tract. The present work explores whether extending the models into the third dimension using data from MRI scans increases the accuracy of the model, and whether the new model is computationally feasible for real-time simulation. It(More)
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