University of Washington
Howard Hughes Medical Institute
S-313 Foege Building
Genome Sciences, Box 355065
Seattle, WA 98195-5065
Phone: (206) 616-4522
Phone: (206) 616-4523
FAX: (206) 543-0754
We are interested in developing biological assays to analyze the function of proteins, often using the yeast Saccharomyces cerevisiae as a model organism for assays that can be applied to proteins from any organism. Current studies include assays to analyze proteins, DNA, RNA and small molecules.
The past decade has seen a profusion of genome sequences, with total DNA sequence accumulation of more than 100 billion bases. Genome sequences have led to the prediction of large complements of proteins. However, the determination of protein function remains a difficult task, given the range of biochemical activities that proteins display, the diverse modifications that a protein can undergo, the multiplicity of proteins potentially encoded by a single gene, and the use of proteins for more than a single function. Our laboratory is interested in developing biological technologies, especially those to analyze protein function. Often we useSaccharomyces cerevisiae (baker's yeast) as the host organism for carrying out protein assays. Yeast—the first eukaryote to be sequenced—has a small number of genes, is highly tractable for experimentation, has numerous sets of available reagents, and is well-established for the analysis of high-throughput data. As a consequence, the set of yeast proteins is particularly advantageous for testing new technologies. In addition, yeast is a convenient host to express proteins from many other organisms.
In the past, we have also used S. cerevisiae to analyze proteins relevant to human disease. Studies have focused on a human polyglutamine-containing protein implicated in neurodegenerative disease, the human Toll-like receptors that mediate innate immunity, the proteins of the malaria parasite Plasmodium falciparum, and yeast proteins that play a role in aging.
Investigator: Dr. Fields is a Professor of Genome Sciences and Medicine (Medical Genetics).
LaCount, D.J., Vignali, M., Chettier, R., Phansalkar, A., Bell, R., Hesselberth, J., Schoenfeld, L.W., Ota, I., Sahasrabuhde, S., Kurschner, C., Fields, S., and Hughes, R. (2005) A protein interaction network of the malaria parasite Plasmodium falciparum. Nature 438:103-107.
Kaeberlein, M., Powers, R.W. III, Steffen, K.K., Westman, E.A., Hu, D., Dang, N., Kerr, E.O., Kirkland, K.T., Fields, S., and Kennedy, B.K. (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310: 1193-1196.
Miller, J.P., Lo, R.S., Ben-Hur, A., Desmarais, C., Stagljar, I., Noble, W.S. and Fields, S. (2005) Large-scale identification of yeast integral membrane protein interactions. Proceedings of the National Academy of Sciences U.S.A. 102: 12123-12128.
Kaeberlein, M., Hu, D., Kerr, E.O., Tsuchiya, M., Westman, E.A., Dang, N., Fields, S. and Kennedy, B.K. (2005) Increased life span due to calorie restriction in respiratory-deficient yeast. PLoS Genetics 1: e69: 614-621.
Brown, V., Brown, R.A., Ozinsky, A., Hesselberth, J.R. and Fields, S. (2006) Binding specificity of Toll-like receptor cytoplasmic domains. European Journal of Immunology 36: 742-753.
Powers, R.W. III, Kaeberlein, M., Caldwell, S.D., Kennedy, B.K. and Fields, S. (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes and Development 20: 174-184.
Jin, F.,Hazbun, T., Michaud, G.A., Salcius, M., Predki, P.F., Fields S. and J. Huang (2006) A pooling-deconvolution strategy for biological network elucidation. Nature Methods 3: 183-189.
Hesselberth, J.R., Miller, J.P., Golob, A., Stajich, J.E., Michaud, G.A. and Fields, S. (2006) Comparative analysis of Saccharomyces cerevisiae WW domains and their interacting proteins. Genome Biology 7: R30.1-R30.15.
Zhang, Z., Hesselberth, J.R. and Fields, S. (2007) Genomewide identification of spliced introns using a tiling microarray. Genome Research 17: 503-509.