Keith Blackwell

Using the model organism C. elegans, we study how regulation of gene expression influences cell development and function. One of our two major areas of interest is in studying specialized mechanisms that regulate gene expression in germline stem cells and the early embryo. In our other major project, we are investigating how a critical cellular defense against oxidative stress functions and is regulated.

In the germline and early embryo, we are studying two mechanisms through which gene expression iscontrolled on a large scale. One of these involves the C. elegans counterpart to P bodies, a recently described RNA-protein structure that may either store or degrade translationally silenced mRNA. We believe that many C. elegans oocyte mRNAs are stored in a translationally silent state in P body-like structures, and that their regulation by P body proteins is important during oogenesis, and later in the developing embryo. Some C. elegans P body proteins are expressed specifically in germ cells, the only self-renewing stem cell population in the organism. One exciting possibility is that some P body functions may be particularly important in stem cells, possibly because stored mRNA may provide a memory of gene expression that could influence downstream differentation steps. Interestingly, we have found that in C. elegans certain P body proteins are important for regulating the frequency of developmental oocyte cell death, which occurs at a similar stage of meiosis in widely divergent organisms. Weare very interested in understanding the connection between mRNA metabolism and this cell death, which we believe may ensure a proper distribution and regulation of key cytoplasmic components during oogenesis. In parallel to this project, we study mechanisms that globally silence transcription during late oogenesis and in the early germline, and activate the transcription repertoire in the early embryo. These last studies are directed towards understanding aspects of germ cell pluripotency, as well as transcription regulation.

Our oxidative stress project is centered around studying the SKN-1 protein. SKN-1 initiates development of the digestive system during the earliest embryonic stages, then later orchestrates a transcriptional response to oxidative stress and reactive toxins that is conserved among eukaryotes. SKN-1 activates detoxification genes in response to certain stresses, and is required for oxidative stress resistance and normal longevity. We are applying the advantages of C. elegans to investigate how SKN-1 promotes stress resistance and longevity, and how this detoxification pathway is controlled by cellular metabolic, stress, and redox signals.