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.

Themes

• 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.

Biography

Education

Ph.D.    Biochemistry             1982     University of Queensland

B.Sc.    (Hons) Biochemistry    1978    University of Queensland

Professional Experience

• Faculty Member, Molecular and Cellular Biology Interdisciplinary Program, University of Washington, Seattle, WA, 2010 - Present
• Affiliate Professor, Departments of Global Health & Medical Education and Biomedical Informatics, University of Washington, Seattle, WA, 2008 - Present
• Adjunct Research Professor, Department of Global Health, University of Washington, 2007 - 2008
• Scientific Director, Protein Production Core, Seattle Biomedical Research Institute, 2007 - Present
• Scientific Director, Bioinformatics Core, Seattle Biomedical Research Institute, 2006 - Present
• Professor, Seattle Biomedical Research Institute, 2004 - Present
• Research Professor, Department of Pathobiology, and Division of Biomedical and Health Informatics, Department of Medical Education and Biomedical Informatics, University of Washington, 2004 - 2008
• Scientific Director, DNA Sequencing Core Facility, Seattle Biomedical Research Institute, 1991 - Present
• Research Professor, Department of Pathobiology, and Adjunct Research Professor, Division of Biomedical and Health Informatics, Department of Medical Education and Biomedical Informatics, University of Washington, 2004 - 2005
• Adjunct Research Associate Professor, Division of Biomedical and Health Informatics, Department of Medical Education and Biomedical Informatics, University of Washington, 2001 - 2004
• Associate Member, Seattle Biomedical Research Institute, 2000 - 2004
• Staff Scientist, Seattle Biomedical Research Institute, 1996 - 2000
• Research Associate Professor, Department of Pathobiology, University of Washington, 1997 - 2004
• Assistant Professor, Department of Pathobiology, University of Washington, Seattle, WA, 1993 - 1997
• Associate Scientist, Seattle Biomedical Research Institute, 1987 - 1996

Select Honors and Awards

• Member, Scientific Committee for 5^th World Congress on Leishmaniasis, 2011 - Present
• Chair-Elect, Division AA of the American Society for Microbiology, 2011-2012
• Member, Scientific Committee for 4^th World Congress on Leishmaniasis, 2008 - 2009
• Leishmaniasis Review panel for Military Infectious Diseases Research Program of the US Army, Navy, and Air Force; Joint Medical Technology Workshop, 2003
• Editorial board, Kinetoplastid Biology and Disease, 2001-2008
• USDA, Sustaining Animal Health and Well-being (study section member), 1999-2001
• NIH, Shared Instrumentation Grants Special Study Section, 1994-1995
• USAID/AIBS, Malaria program review panel,1988-1992

Staff

Myler Lab 

Robin Stacy, Senior Project Manager

Andrew Haydock, Research Associate

Loren Baugh, Staff Scientist

Katherine Guild, Graduate Student

Vickie Satele, Lab Assistant

Wen-Wai Yim, Rotating Graduate Student

Monica Terrao, Visiting Scholar 

Sequencing Core

Ellen Sisk, Core Manager

Lyudmila Wold, Technician

Protein Production Core

Sunny Zhang, Core Manager

Wenjin Guo, Senior Protein Expression & Purification Specialist

Kaitlin Tompkins, Research Technician II

Elizabeth Mundt, Research Technician II

Micah Ferrell, Research Technician II

Ariel Abromov, Research Technician I

Bioinformatics Core

Isabelle Phan, Core Manager

Sandhya Subramanian, Senior Bioinformatics Applications Specialist

Gowthaman Ramasamy, Bioinfomatics Research Specialist

Lisabeth Cron, Bioinformatics System Programmer

Christian Olsen, Biocurator

Wonjong Moon, Bioinfomatics Research Specialist  

Accomplishments & Collaborations

• Completed Tritryp genome sequences, providing the basis for discovery of new anti-trypanosomatid drugs
• Elucidated genome-wide transcription map of L. major and L. donovani
• Revealed hundreds of proteins that are up- or down-regulated during the transition between insect and mammalian stages of L. donovani
• Leading SSGCID effort which has already solved more than 450 3-dimensional protein structures from category A-C biodefense, emerging and re-emerging infectious disease organisms