Mammalian physiology is synchronized into 24-hour rhythms that coincide with the solar day by an intrinsic molecular clock. As a global regulator of homeostasis, disruption of the circadian clock has profound consequences on human health, leading to depression, metabolic syndromes, cancer, and premature aging. The Partch lab studies how the 24-hour periodicity of this molecular clock is generated and how it integrates with the cell cycle to limit proliferation using cell biology, biochemistry and biophysical techniques. They are also interested in chemical biology approaches to modulate clock timing with structurally informed in vitro and cell-based screening platforms.
Published in Biochemistry
Cryptochromes are blue-light photoreceptors that regulate a variety of responses such as growth and circadian rhythms in organisms ranging from bacteria to humans. Cryptochromes share a high level of sequence identity with the light-activated DNA repair enzyme photolyase. Photolyase uses energy from blue light to repair UV-induced photoproducts in ...
Published in Trends in Biochemical Sciences
It is widely recognized that BMAL1 is an essential subunit of the primary transcription factor that drives rhythmic circadian transcription in the nucleus. In a surprising turn, Lipton et al. now show that BMAL1 rhythmically interacts with translational machinery in the cytosol to stimulate protein synthesis in response to mTOR signaling.
Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5.
Published in Proceedings of the National Academy of Sciences
The molecular oscillator that drives circadian rhythmicity in mammals obtains its near 24-h periodicity from posttranslational regulation of clock proteins. Activity of the major clock kinase casein kinase I (CKI) epsilon is regulated by inhibitory autophosphorylation. Here we show that protein phosphatase (PP) 5 regulates the kinase activity of CK...