Molecular Biosciences
Regulation of Genome Expression
Dr. John Wyrick and his collaborators are using DNA microarray technology to investigate how covalent modifications of histone proteins regulate gene expression in eukaryotic cells. Histone modifications, such as histone acetylation, phosphorylation, and methylation are coded instructions that are read by cells during the gene regulation process. Unlike the genetic code, however, the histone code has yet to be deciphered. To crack the histone code, we have begun to analyze how histone modifications regulate genome expression in yeast, which serves as an experimental model for human cells. Since aberrant patterns of histone modifications has been linked to development of cancer and other human diseases, completion of this research should give new insight into these diseases and could facilitate the development of novel therapeutic agents.
Our strategy incorporates the powerful combination of yeast genetics and functional genomics to dissect how histone modifications regulate gene expression. We are using yeast genetics to systematically mutate each histone modification site, both singly and in combination. The phenotype of these mutants are being investigated using three different functional genomic assays:
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cDNA microarray analysis
To identify changes in global mRNA levels.
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Genome-wide location analysis
To determine changes in protein binding to promoter DNA. -
Genomic chromatin analysis
To assay for changes in genomic chromatin structure.
These experiments involve the development of novel functional genomics tools. Currently, we are using DNA microarray instruments and equipment available in Dr. Wyrick’s laboratory as well as the core DNA microarray facility at Washington State University. The microarray data generated in these experiments will be analyzed using various bioinformatics tools, including an online relational database. This work is being done in collaboration with Dr. Curtis Dyreson, a faculty member in the School of Electrical Engineering and Computer Science at Washington State University and an expert on Web databases and data warehousing.
Analysis of the microarray data from these experiments will provide a conceptual framework for understanding the mechanisms and rules governing how the histone code regulates gene expression. This project will advance scientific knowledge of how the histone code controls gene expression in eukaryotic cells and how aberrant regulation of histone modifications can lead to cancer and other diseases.
Contact Information
John J. Wyrick, Ph.D.
School of Molecular Biosciences
Washington State University
PO Box 644660
Pullman, WA 99164-4660
Tel: 509-335-8785
Fax: 509-335-9688
E-mail: jwyrick@wsu.edu
Web:
molecular.biosciences.wsu.edu/faculty/wyrick.html
Health and Life Sciences
Genomics, Proteomics, and Informatics
Washington State University is committed to building on its existing strengths in genomics, proteomics, and informatics. The scientists highlighted here provide a sampling of both established and recently added WSU research programs in these areas. Each of these scientists and their many collaborators both at WSU and elsewhere are making important impacts in their respective areas. A recently developed strategic plan at Washington State University identifies biotechnology as a significant focus for research development, so the current strengths are priming the system for very rapid growth.
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Dr. John Wyrick received a Ph.D. in biology from the Massachusetts Institute of Technology in 2001. As a graduate student under the direction of Dr. Richard Young, Dr. Wyrick developed and used DNA microarray technology to investigate how transcription factors regulate the expression of the yeast genome. He then worked as a postdoctoral scholar in Dr. Elliot Meyerowitz’s laboratory at the California Institute of Technology. There he developed computational and bioinformatics tools to gain insight into transcriptional regulation in plants. Currently, Dr. Wyrick is using functional genomic tools to investigate the links between chromatin structure and transcription regulation. He has authored papers that have been published in Cell, Nature, and Science, including an article that was listed by The Scientist magazine as among the most important peer-reviewed papers published within the field of Molecular Medicine. |
