T. Keith Blackwell
Department of Genetics
Joslin Diabetes Center
One Joslin Place, Room 655B
Boston, MA 02215
Tel: (617) 309-2760
Fax: (617) 309-3403
3 postdoctoral fellows, 3 graduate students
We study how regulation of gene expression influences cell development and function, using the model organism C. elegans. One of our two major areas of interest is in understanding how a major cellular defense against oxidative stress functions and is regulated, and how this pathway delays aging. In our second area of interest, we study mechanisms that regulate gene expression in germline stem cells and the early embryo.
Our studies of stress and aging are centered around the transcription factor SKN-1, which orchestrates a transcriptional response to oxidative stress and reactive toxins that is conserved among eukaryotes. SKN-1 induces detoxification genes in response to certain stresses, and is required for normal longevity and oxidative stress resistance. It is regulated by insulin/IGF-1 signaling (IIS), and contributes to the increased stress-resistance and longevity seen when IIS is reduced. We are applying the advantages of C. elegans to investigate how SKN-1 functions and promotes longevity, and how this detoxification pathway is controlled.
Our other major area of interest is investigation of mechanisms that regulate gene expression in the germline, a model stem cell population. A conserved feature of oocyte development is that many mRNAs are “stored” in a translationally quiescent state, then reactivated during later stages or in the embryo. We are studying how mechanisms that are associated with mRNA-protein P-bodies contribute to localization, stabilization, translational regulation, and turnover of these maternal mRNAs. We are also interested in mechanisms that globally silence transcription during late oogenesis and in the early germline, and activate the transcription repertoire in the early embryo.
- Walker AK, Boag PR, Blackwell TK. (2007) Transcription reactivation steps stimulated by oocyte maturation in C. elegans. Dev. Biol. 304, 382-393.
- Tullet JMA, Hertweck M, An JH, Baker J, Hwang JY, Liu S, Oliveira RP, Baumeister R, Blackwell TK. (2008) Direct inhibition of the longevity promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell, 132, 1025-1038.
- Boag PR, Atalay A, Robida S, Reinke V, Blackwell TK. (2008) Protection of specific maternal mRNAs by the P-body protein CGH-1 (Dhh1/RCK) during C. elegans oogenesis. J. Cell Biol., 182, 543-557.
- Oliveira RP, Porter Abate J, Dilks K, Landis J, Ashraf J, Murphy CT, Blackwell TK. (2009) Condition-adapted stress and longevity gene regulation by Caenorhabditis elegans SKN-1/Nrf. Aging Cell, 8, 524-541.
- Wang J, Robida-Stubbs S, Tullet JMA, Rual JF, Vidal M, Blackwell TK. (2010) RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLOS Genetics, in press.
BBS webpage updated 6/16/2010