Research Experience in Bioinformatics for Undergraduates

The Basic Local Alignment Search Tool (BLAST) is a sequence comparison algorithm used to search sequence databases for alignments of some portion of nucleic acid or protein sequences. This is a compute-intensive operation that can take from several minutes to hours depending on the computer that runs it. During the summer of 2004, as a part of the Research Experience in Bioinformatics for Undergraduates at UK, we participated in extending and testing the software for BooleanBlast. While BLAST allows for a search of only a single sequence, BooleanBlast adds the functionality to use queries of arbitrary complexity. For example it can process queries such as, find sequence A AND sequence B OR sequence C, BUT NOT sequence D, et cetera. With the BooleanBlast, it is possible to create and use expressive BLAST queries based on Boolean combinations. Our group of Bioinformatics for Undergraduates focused on testing and providing user friendly graphical interfaces (GUIs). We developed and implemented for BooleanBlast two complete user interfaces, one similar to a traditional search engine, the other giving the user a more guided experience. In the process of adding these interfaces, the internal code of BooleanBlast was significantly tested and improved. As a result of the Summer Bioinformatics Program for Undergraduates, BooleanBlast offers a search tool with an intuitive GUI that is both flexible and powerful

A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis

The immunoproteasome, a distinct class of proteasome found predominantly in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on class I major histocompatibility complexes (MHC-I). However, a specific role for the immunoproteasome in regulating other facets of immune responses has not been established. We describe here the characterization of PR-957, a selective inhibitor of low-molecular mass polypeptide-7 (LMP7, encoded by Psmb8), the chymotrypsin-like subunit of the immunoproteasome. PR-957 blocked presentation of LMP7-specific, MHC-I-restricted antigens in vitro and in vivo. Selective inhibition of LMP7 by PR-957 blocked production of interleukin-23 (IL-23) by activated monocytes and interferon-gamma and IL-2 by T cells. In mouse models of rheumatoid arthritis, PR-957 treatment reversed signs of disease and resulted in reductions in cellular infiltration, cytokine production and autoantibody levels. These studies reveal a unique role for LMP7 in controlling pathogenic immune responses and provide a therapeutic rationale for targeting LMP7 in autoimmune disorders