A diverse array of organisms including prokaryotic and eukaryotic microbes, plants, and animals display daily rhythms in physiology, metabolism and/or behavior. These rhythms are not passively driven by environmental cycles of light and temperature, but are actively controlled by endogenous circadian clocks that are set by environmental cycles, keep time in the absence of environmental cues, and activate overt physiological, metabolic and behavioral rhythms at the appropriate time of day. This remarkable conservation of circadian clock function through evolution suggests that maintaining synchrony with the environment is of fundamental importance. Our understanding of the circadian clock is particularly important for human health and well-being. The clearest examples of circadian clock dysfunction are those that result in abnormal sleep-wake cycles, but clock disturbances are also associated with other ailments including epilepsy, cerebrovascular disease, depression, and seasonal affective disorder. The realization that disorders of the sleep-wake cycle such as Familial Advanced Sleep Phase Syndrome can result from alterations in clock gene function underscores the clinical importance of understanding the molecular organization of the circadian system.
Work in my laboratory focuses on defining the molecular mechanisms that drive circadian clock function in the fruit fly, Drosophila melanogaster. We previously found that the core timekeeping mechanism is based on core and interlocked transcriptional feedback loops. Our studies currently focus on (1) defining post-translational regulatory mechanisms that operate in the core loop to set the 24 hour period, (2) determining whether interlocked loops are important for circadian timekeeping and/or output, (3) understanding how circadian oscillator cells are determined during development, and (4) defining mechanisms that control rhythms in olfactory and gustatory physiology and behavior.
- Howard Hughes Medical Institute - (Chevy Chase, Maryland, United States), Postdoctoral Training 1991
- Ph.D. in Genetics, Indiana University Bloomington - (Bloomington, Indiana, United States) 1987
- B.S. in Biology, Southern Methodist University - (Dallas, Texas, United States) 1982
- Fuentes, N. R., Mlih, M., Barhoumi, R., Fan, Y. Y., Hardin, P., Steele, T. J., ... Chapkin, R. S. (2018). Long-chain n-3 fatty acids attenuate oncogenic kras-driven proliferation by altering plasma membrane nanoscale proteolipid composition. CANCER RESEARCH. 78(14), 3899-3912.
- Chatterjee, A., Lamaze, A., De, J., Mena, W., Chélot, E., Martin, B., ... Rouyer, F. (2018). Reconfiguration of a Multi-oscillator Network by Light in the Drosophila Circadian Clock. Current biology : CB. 28(13), 2007-2017.e4.
- Siwicki, K. K., Hardin, P. E., & Price, J. L. (2018). Reflections on contributing to “big discoveries” about the fly clock: Our fortunate paths as post-docs with 2017 Nobel laureates Jeff Hall, Michael Rosbash, and Mike Young. Neurobiology of Sleep and Circadian Rhythms.
- Liu, T., Mahesh, G., Yu, W., & Hardin, P. E. (2017). CLOCK stabilizes CYCLE to initiate clock function in Drosophila. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES. 114(41), 10972-10977.
- Agrawal, P., Houl, J. H., Gunawardhana, K. L., Liu, T., Zhou, J., Zoran, M. J., & Hardin, P. E. (2017). Drosophila CRY Entrains Clocks in Body Tissues to Light and Maintains Passive Membrane Properties in a Non-clock Body Tissue Independent of Light. Current biology : CB. 27(16), 2431-2441.e3.
- Wangjie, Y. u., & Hardin, P. E. (2013). An RNAi screen of protein kinase genes identifies novel components of the circadian oscillator in Drosophila. JOURNAL OF PHYSIOLOGICAL SCIENCES. 63, S111-S111.
- Benito, J., Zheng, H., Ng, F. S., & Hardin, P. E. (2007). Transcriptional feedback loop regulation, function, and ontogeny in Drosophila. Symposia on Quantitative Biology. 72(1), 437-444.
- Ng, F. S., Houl, J. H., Francis, C., Callaerts, P., & Hardin, P. E. (2006). CLOCK expression and regulation during development in Drosophila. Journal of Neurogenetics. 20(3-4), 189-189.
- Zwiebel, L. J., Hardin, P. E., Hall, J. C., & Rosbash, M. (1991). Circadian oscillations in protein and mRNA levels of the period gene of Drosophila melanogaster. Biochem Soc Trans. 19(2), 533-537.
- Gunawardhana, Kushan Lakshitha (2018-05). Characterization of Vrille Function in the Drosophila Circadian Clock. (Doctoral Dissertation)
- Liu, Tianxin (2017-08). Circadian Clock Development and Initiation in Drosophila melanogaster. (Doctoral Dissertation)
- Caster, Courtney Marie (2017-08). Investigating the Evolution of the Molecular Clock Mechanism Using the Housefly, Musca domestica. (Master's Thesis)
- Zhou, Jian (2017-08). Characterizing the Function of Clockwork Orange in the Circadian Feedback Loops in Drosophila melanogaster. (Doctoral Dissertation)
- Agrawal, Parul (2016-08). Characterizing Novel Circadian Clock Functions for Drosophila Phosphatases and Non-clock Functions for Circadian Photoreceptors. (Doctoral Dissertation)