307 Westlake Ave. N.Suite 500Seattle, WA 98109-5219
The Myler laboratory is devoted to discovery research aimed at developing novel therapeutic strategies against global infectious disease. Our work focuses on using genomic, bioinformatic, and molecular approaches to study gene and protein structure in bacterial, eukaryote and viral pathogens. In collaboration with Ken Stuart (at Seattle BioMed), we played a key role in sequencing the Trypanosoma and Leishmania genomes, and are actively engaged in the on-going curation/annotation of several additional trypanosomatid genomes. These protozoan parasites are remarkable in that their genomes are arranged into <200 polycistronic transcription units (PTUs) of protein-coding genes, interspersed by RNA genes. We used genome-scale approaches (such as RNA-seq and chromatin immunoprecipitation) to define the initiation and termination sites of these PTUs, and recently obtained NIH funding to elucidate the role of an unusual modified DNA base J (β-d-glucopyranosyloxymethyluracil) in transcription termination. In collaboration with Dan Zilberstein (at the Technion-Israel Institute of Science), we used microarrays, RNA-seq and tandem mass spectrometry to identify and characterize the changes in gene expression that occur during differentiation from the insect form (promastigotes) to the mammalian form (amastigotes) of L. donovani and are currently elucidating the signaling pathways involved in this process. In collaboration with Marilyn Parsons (at Seattle BioMed), we recently used ribosome profiling to interrogate the role of translational regulation in gene expression in Trypanosoma and Leishmania, andare currently adapting this technology for use in Plasmodium. Dr. Myler is also Director of the NIAID-funded Seattle Structural Genomics Center for Infectious Disease (SSGCID), which includes investigators at Seattle BioMed, Emerald BioStructures, University of Washington and Pacific Northwest National Laboratories. To-date, SSGCID has used X-ray crystallography and NMR to solve over 600 protein structures from Biodefense and Emerging Infectious Disease pathogens, as well as other parasites. These protein structures serve as a blueprint for structure-based drug development, and SSGCID makes ~7000 expression clones and ~3000 purified proteins freely available to the scientific community to facilitate vaccine development and other basic research.
Copyright © 2003-2014 Molecular & Cellular Biology Program, University of Washington
Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research