n2a2bfb97 Professor

Research in the Bell-Pedersen lab focuses on determining how the circadian clock functions in organisms to regulate daily rhythms in gene expression, behavior, and physiology. The molecular clock in higher eukaryotes involves a master clock in the brain regulating clocks in peripheral tissues, posing significant obstacles for understanding circadian output mechanisms. Thus, a major strength of our work is using a single-celled model eukaryote, Neurospora crassa, to elucidate the underlying mechanisms of rhythmic gene expression and protein synthesis. Clock dysfunction in humans is associated with a wide range of diseases, including cardiovascular disease, cancer, metabolic disorders, mental illness, sleep disorders, and aging. In addition, daily changes in metabolism and cell division rates influence the efficacy and toxicity of many pharmaceuticals, including cancer drugs. Therefore, knowing how clocks work to control rhythmic gene expression, and what they regulate, is critical for the development of therapeutics. Research to understand clock-controlled rhythmic gene expression has focused primarily on transcriptional mechanisms, and little was known about posttranscriptional control. We discovered that the clock regulates highly conserved translation initiation and elongation factors, tRNA synthetase levels, and ribosome heterogeneity. This regulation determines what mRNAs are rhythmically translated and the accuracy of the translation process (translation fidelity). We are capitalizing on these exciting discoveries to determine how the clock regulates translation fidelity. These studies will provide the foundation for understanding the impact of daily rhythms in translation fidelity on protein diversity beyond what is encoded for in the genome.