Jeffrey Laney, Ph.D.
Assistant Professor of Medical Science
Molecular Biology, Cell Biology, & Biochemistry
Work: +1 401-863-1789
Rapid and accurate transitions between different gene expression programs are vitally important for cells to respond to changing metabolic requirements, developmental programs, and extracellular stimuli. The goal of our research program is to understand how a cell exploits the dynamic process of ubiquitin-mediated proteolysis to change patterns of gene expression and switch between alternate phenotypic states.
BiographyJeff Laney received his B.S. degrees in Biochemistry and Biological Sciences from Florida State University in 1989. His graduate work in Molecular Biophysics and Biochemistry at Yale University (PhD, 1995) with Dr. Mark Biggin focused on transcriptional regulation during early Drosophila development. From 1997 to 2002, he was an American Cancer Society Postdoctoral Fellow with Dr. Mark Hochstrasser at the University of Chicago and Yale University, where he initiated his studies on regulated protein degradation and gene expression in the yeast Saccharomyces cerevisiae. He joined the Brown faculty in 2002.
Research DescriptionWe are investigating the role that the ubiquitin proteolytic system plays in the dynamics of gene expression by studying the mating-type determination and switching system of the yeast Saccharomyces cerevisiae. This model eukaryote exists as one of three cell types: two haploid variants (a and alpha) that can mate with each other to form the third type, a non-mating a/alpha diploid. These distinct cellular phenotypes are determined by the allele present at the mating-type (MAT) locus, which encodes a group of master regulatory transcription factors. Remarkably, in many strains, the mating phenotype is unstable, and cells of one haploid mating-type can differentiate into the opposite cell type. The phenotypic changes associated with such a switch occur during a single division cycle, suggesting that the transcription factors controlling mating-type are short-lived. Indeed, direct assays of protein stability show that each of these factors is rapidly degraded, with the highly conserved ubiquitin-proteasome pathway directing their proteolysis.
We have found that strains genetically impaired in the ubiquitin-dependent proteolysis of alpha2, one of the MAT-encoded transcription factors, exhibit profound defects in their ability to undergo an alpha-to-a phenotypic change. Notably, the genetic transposition process of replacing one MAT allele with the other appears normal, indicating that alpha2 turn-over per se plays a key role in this cellular differentiation event. Thus, ubiquitin-mediated degradation is used to erase a pre-existing network of regulatory transcription factors, so that a new system of regulators can effectively establish a different phenotypic state. Such a mechanism is likely to operate during a number of diverse developmental transitions, ranging from the establishment of neuronal identity in insects to the differentiation of lymphocytes in mammals.
We are extending this work by characterizing the changes that occur when the repressed mating-type genes reactivate and switch to an expressed state. Our goal is to understand, at a mechanistic and molecular level, the functional dynamics of these gene expression programs. In doing so, we hope to provide insight into the role of the ubiquitin system in the phenotypic changes that occur during cell growth and development.
Grants and AwardsBasil O'Connor Starter Scholar Research Award - March of Dimes
American Cancer Society Postdoctoral Fellow
Funded ResearchProteolysis of Eukaryotic Differentiation Factors
March of Dimes Birth Defects Foundation
PI: Jeffrey Laney
Proteolytic Control of Yeast Cell Type
NIH/NIGMS (R01 GM071764)
- Wilcox, A.J. and Laney, J.D. (2009). A ubiquitin-selective AAA-ATPase mediates transcriptional switching by remodeling a repressor-promoter DNA complex. Nature Cell Biol. 11, 1481-1486. (2009)
- Laney, J.D., Mobley, E.F., and Hochstrasser, M. (2006) The short-lived Matalpha2 transcriptional repressor is protected from degradation in vivo by interactions with its corepressors Tup1 and Ssn6. Mol. Cell Biol 26, 371-380. (2006)
- Laney, J.D. and Hochstrasser, M. (2004) Ubiquitin-dependent control of development in Saccharomyces cerevisae. Curr. Opin. Micro. 7, 647-654 (2004)
- Laney, J.D. and Hochstrasser, M. (2003). Ubiquitin-dependent degradation of the yeast Matalpha2 repressor enables a switch in developmental state. Genes & Dev. 17, 2259-2270. [Subject of Perspective, Genes & Dev. 17, 2201-2204 (2003).] [Subject of Dispatch, Curr. Biol. 24, 200-213 (2004).] (2003)
- Laney, J.D. and Hochstrasser, M. (2002). Assaying protein ubiquitination in S. cerevisiae. Methods Enzymol. 351, 248-257 (2002)
- Hur, M.-W., Laney, J.D., Jeon, S.-H., Ali, J., Biggin, M.D. (2002). Zeste maintains repression of Ultrabithorax transgenes: support for a new model of Polycomb repression. Development 129, 1339-1343. (2002)
- Laney, J.D. and Hochstrasser, M. (1999). Substrate Targeting in the Ubiquitin System. Cell 97, 427-430. (1999)
- Hochstrasser, M., Johnson, P.R., Arendt, C.S., Amerik, A.Yu., Swaminathan, S., Swanson, R., Li, S.J., Laney, J., Pals-Rylaarsdam, R., Nowak, J., Connerly, P.L. (1999). The Saccharomyces cerevisiae ubiquitin-proteasome system. Philos. Trans. R Soc. Lond B Biol. Sci. 354, 1513-22. (1999)
- Laney, J.D. and Biggin, M.D. (1997). Zeste-mediated activation by an enhancer is independent of cooperative DNA binding in vivo. Proc. Natl. Acad. Sci. 94, 3602-3604. (1997)
- Laney, J.D. and Biggin, M.D. (1996). Redundant control of Ultrabithorax by zeste involves functional levels of Zeste protein binding at the Ultrabithorax promoter. Development 122, 2303-2311. (1996)
- Laney, J.D. and Biggin, M.D. (1992). zeste, a nonessential gene, potently activates Ultrabithorax transcription in the Drosophila embryo. Genes & Dev. 6, 1531-1541. (1992)