Stanley Fields
Professor of Genome Sciences and of Medicine
Adjunct Professor of Microbiology

The Fields laboratory is interested in developing technologies, especially those to analyze protein function. In the last decade, genome sequences have led to the prediction of large complements of proteins, ranging from a few thousand in bacterial species to more than 20,000 for humans and other mammalian species. However, the determination of protein function remains a difficult task, given the tremendous range of biochemical activities that proteins display, the diverse modifications that a protein can undergo during its lifetime, the multiplicity of proteins potentially encoded by a single gene, and the use of proteins for more than a single function.

For many of our technology efforts, we use the unicellular eukaryote Saccharomyces cerevisiae (baker's yeast) as the host organism for carrying out protein assays. Yeast has a small number of genes, is highly tractable for experimentation, and has been used to derive numerous sets of reagents and high-throughput data. We are using yeast to analyze protein-protein and RNA-protein interactions, to characterize introns on a genomewide basis, to develop approaches to identify substrates of ubiquitin E3 ligases, to profile metabolites, to examine chromosome conformation and chromatin structure, and to identify proteins that promote recombination. We are using in vitro technologies to couple DNA fragments, the mRNA transcribed from this DNA, and the protein translated from this RNA to provide the basis for activity screens and binding selections.

We have also used S. cerevisiae for the analysis of proteins relevant to human disease. Past 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.

Publications:

DeVit, M., Cullen, P.J., Branson, M., Sprague, G.F., Jr. and Fields, S. (2005) Forcing interactions as a genetic screen to identify proteins that exert a defined activity. Genome Research 15: 560-565.

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. Proc. Natl. Acad. Sci. U.S.A. 102:12123-12128.

LaCount, D.J., Vignali, M., Chettier, R., Phansalkar, A., Bell, R., Hesselberth, J., Schoenfeld, L.W., Ota, I., Sahasrabudhe, 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 210: 1193-1196.

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 Huang, J. (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.

additional publication listings available via PubMed