Spinal and Bulbar Muscular Atrophy (SBMA)

Spinal and bulbar muscular atrophy (SBMA) is an X-linked disease that causes degeneration of motor neurons, with adult onset and slow progression. There is currently no effective treatment. SBMA is caused by a polyglutamine expansion in the androgen receptor (AR), and one of the hallmarks of the disease is aggregation of the toxic protein. However, the role of the aggregates is still not clear. Inclusions, which are microscopically visible aggregates of protein and are observed in SBMA, may be a protective response to isolate toxic protein from the cellular environment. Smaller, microscopically invisible oligomers might be the toxic form of the protein.

The molecule B2 was found to increase inclusion formation and decrease toxicity in a cell model of Huntington's disease, another polyglutamine expansion disease with protein aggregation. Our goal was to determine the effect of B2 on protein aggregation by western blot in a cell model of SBMA. In preliminary experiments, we discovered that B2 decreases the amount of AR aggregation on the western blot, perhaps promoting sequestration into inclusions. In the course of these experiments, I learned techniques ranging from the amplification of DNA through bacteria, treatment of cell cultures, collection of protein samples, western blot, filter retardation assay, immunocytochemistry, and the analysis of results. In addition to these basic lab procedures, one of the more important skills I learned was how to approach a question scientifically. Reading scientific literature about SBMA greatly expanded my ability to develop hypotheses and experiments based on what others have discovered. I learned through weeks of unclear results how to work through issues that arise and vary the experimental approach to get more consistent, reliable data. Although the lab techniques I learned will be valuable throughout my scientific career, the ability to think critically and reason through problems is a skill I began to develop at the NIH that will benefit me the most in future research.