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Biomedical subjects

Arthur Olson

Publications and source records attributed to Arthur Olson.

3 recordsLinked to original sources

Details of Toll-like receptor:adapter interaction revealed by germ-line mutagenesis.

The immunovariant N-ethyl-N-nitrosourea-induced mutations Pococurante (Poc) and Lackadaisical were found to alter MyD88, creating striking receptor-selective effects. Poc, in particular, prevented sensing of all MyD88-dependent Toll-like receptor (TLR) ligands except diacyl lipopeptides. Furthermore, Poc-site and classical BB loop mutations caused equivalent phenotypes when engrafted into any TLR/IL-1 receptor/resistance (TIR) domain. These observations, complemented by data from docking studies and site-directed mutagenesis, revealed that BB loops and Poc sites interact homotypically across the receptor:adapter signaling interface, whereas the C-terminal alpha(E)-helices support adapter:adapter and receptor:receptor oligomerization. We have thus defined the TIR domain surface that mediates association between TLRs and MyD88 and the surface required for MyD88 or TLR oligomerization. Moreover, MyD88 engages individual TLRs differently, suggesting the feasibility of selective pharmacologic TIR domain receptor blockade.

Adaptor Proteins, Signal Transducing↗

Tangible interfaces for structural molecular biology.

The evolving technology of computer autofabrication makes it possible to produce physical models for complex biological molecules and assemblies. Augmented reality has recently developed as a computer interface technology that enables the mixing of real-world objects and computer-generated graphics. We report an application that demonstrates the use of autofabricated tangible models and augmented reality for research and communication in molecular biology. We have extended our molecular modeling environment, PMV, to support the fabrication of a wide variety of physical molecular models, and have adapted an augmented reality system to allow virtual 3D representations to be overlaid onto the tangible molecular models. Users can easily change the overlaid information, switching between different representations of the molecule, displays of molecular properties, or dynamic information. The physical models provide a powerful, intuitive interface for manipulating the computer models, streamlining the interface between human intent, the physical model, and the computational activity.

Computer-Aided Design↗