Ph.D. Johns Hopkins University
Our lab is investigating the molecular and cellular mechanisms of circadian rhythms, which have periods of approximately 24 hours and are found in both unicellular and multicellular organisms. For example, human sleep/wake behavior is a circadian rhythm. While responsive to light and temperature cues, circadian rhythms are known to be generated within the organism because they persist under constant environmental conditions. Recently, there have been major advances in our understanding of the underlying cellular and molecular mechanisms that generate these "endogenous clocks". These advances have been possible because of genetic approaches, which require the isolation and analysis of mutations affecting circadian rhythms. Our research has identified several such mutations in the model organism Drosophila melanogaster, which is perhaps the most well developed metazoan genetic system. Molecular cloning of the Drosophila clock genes has demonstrated that two of these genes regulate their own rhythmic expression. Other mutations have identified circadian transcription factors, photoreceptors and a protein kinase, which is the principal focus of our work. Using a combination of genetic, biochemical and immunocytochemical approaches, our lab is investigating how all of these components interact with the protein kinase to produce a functional clock. We also are investigating the role of this protein kinase in vertebrate clocks, which have a mechanism similar to the Drosophila one.Selected Publications
Preuss F, Fan JY, Kalive M, Bao S, Schuenemann E, Bjes E, Price JL. (2004). Drosophila doubletime mutations which either shorten or lengthen the period of circadian rhythms decrease the kinase activity of casein kinase I. Mol Cell Biol 24:886-898.
Muskus MJ, Preuss F, Fan JY, Bjes ES, Price JL. (2007). Drosophila DBT lacking protein kinase activity produces long-period and arrhythmic circadian behavioral and molecular rhythms. Mol Cell Biol 27: 8049-8064.
Fan JY, Preuss F, Muskus MJ, Bjes ES, Price JL. (2009). Drosophila and vertebrate casein kinase Id exhibits evolutionary conservation of circadian function. Genetics 181:139-152.