Professor, Seattle Biomedical Research Institute
Research Professor, Department of Global Health, Department of Medical Education and Biomedical Informatics, University of Washington
Area of Expertise: leishmaniasis, malaria, stuctural biology, bioinformatics, genomics, emerging infections, drug discovery
The Myler laboratory is devoted to the discovery of novel drug and vaccine strategies against global infectious disease. Our work focuses on using molecular, genomic and bioinformatic approaches to study gene expression in Leishmania and Trypanosoma and using high-throughput techniques to elucidate the protein structure in bacterial, eukaryote and viral pathogens.
In 2005, as part of an international collaboration with the Wellcome Trust Sanger Institute, The Institute for Genome Research and the Karolinska Institute, we completed sequencing the genomes of three trypanosomatid parasites (Leishmania major, Trypanosoma cruzi and T. brucei). These projects (which are a joint effort with Ken Stuart) involved establishing a high-throughput sequencing capacity at Seattle BioMed, as well as a substantial bioinformatics capability.
The “Tritryp” genome sequences revealed unusual gene organization in trypanosomatids: the protein-coding genes are arranged in long polycistronic gene clusters, suggesting that these parasites employ unusual methods of transcription. Our laboratory seeks to elucidate the molecular mechanisms involved in RNAPII-mediated transcription of protein-coding genes in Leishmania. This research utilizes genome-scale approaches such as high throughput sequencing based transcript mapping and chromatin immunoprecipitation (ChIP-chip), as well as more traditional molecular approaches such as electrophoretic mobility shifts assays, affinity chromatography, and in vitro transcription.
In another project (in collaboration with Dan Zilberstein at the Technion Institute in Israel), we are using genome-wide approaches, such as RNA-seq and tandem mass spectrometry, to identify changes in gene expression during differentiation from the insect form (promastigotes) to the mammalian form (amastigotes) of L. donovani and to elucidate the signaling pathways involved in this process.
We have recently been awarded a large contact from NIAID to establish the Seattle Structural Genomics Center for Infectious Disease. The goal of this project, which involves collaboration with investigators at Emerald Biostructures, the University of Washington and Pacific Northwest National Laboratory, is to use state-of-the-art structural genomics technologies to create a collection of three dimensional protein structures from NIAID Category A-C pathogens and organisms causing emerging or re-emerging infectious diseases. The protein structures will be made available to the broad scientific community, where they will serve as a blueprint for structure-based drug development, as well as facilitating vaccine development and other basic research.
- regulation of gene expression in protozoan parasites
- genomics and bioinformatics
- high throughput structural biology
Support for Dr. Myler’s current research is provided by the National Institutes of Health (NIH) and the US-Israel Binational Science Foundation.